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Latest Publications and Scientific Information
Publications are posted by date. They are searchable by keyword using the Find function. Pressing CTRL+F brings up a search box at the upper right side of the page. Type the keyword in the box and press enter. The keyword will be highlighted as it appears in the publications.
January 11, 2023
Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses
The characteristics of antibodies that broadly neutralize coronaviruses are poorly understood. Here, Dacon et al.identify a class of stem helix-specific monoclonal antibodies from COVID-19 convalescent donors that neutralize diverse betacoronaviruses, use an IGHV1-46/IGKV3-20 gene signature, and bind in a conserved manner to the spike protein.
December 20, 2022
Impact of SARS-CoV-2 exposure history on the T cell and IgG response
Multiple SARS-CoV-2 exposures, from infection or vaccination, can potently boost spike antibody responses. Less is known about the impact of repeated exposures on T cell responses. Here, we compare the prevalence and frequency of peripheral SARS-CoV-2-specific T cell and IgG responses in 190 individuals with complex SARS-CoV-2 exposure histories. As expected, an increasing number of SARS-CoV-2 spike exposures significantly enhances the magnitude of IgG responses, while repeated exposures improve the number of T cell responders but have less impact on SARS-CoV-2 spike-specific T cell frequencies in the circulation. Moreover, we find that the number and nature of exposures (rather than the order of infection and vaccination) shape the spike immune response, with spike-specific CD4 T cells displaying a greater polyfunctional potential following hybrid immunity compared to vaccination only. Characterizing adaptive immunity from an evolving viral and immunological landscape may inform vaccine strategies to elicit optimal immunity as the pandemic progresses.
December 19, 2022
Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of children
Most studies of adaptive immunity to SARS-CoV-2 infection focus on peripheral blood, which may not fully reflect immune responses at the site of infection. Using samples from 110 children undergoing tonsillectomy and adenoidectomy during the COVID-19 pandemic, we identified 24 samples with evidence of previous SARS-CoV-2 infection, including neutralizing antibodies in serum and SARS-CoV-2-specific germinal center and memory B cells in the tonsils and adenoids. Single-cell B cell receptor (BCR) sequencing indicated virus-specific BCRs were class-switched and somatically hypermutated, with overlapping clones in the two tissues. Expanded T cell clonotypes were found in tonsils, adenoids and blood post-COVID-19, some with CDR3 sequences identical to previously reported SARS-CoV-2-reactive T cell receptors (TCRs). Pharyngeal tissues from COVID-19-convalescent children showed persistent expansion of germinal center and antiviral lymphocyte populations associated with interferon (IFN)-γ-type responses, particularly in the adenoids, and viral RNA in both tissues. Our results provide evidence for persistent tissue-specific immunity to SARS-CoV-2 in the upper respiratory tract of children after infection.
The potential impact of nanomedicine on COVID-19-induced thrombosis
Extensive reports of pulmonary embolisms, ischaemic stroke and myocardial infarctions caused by coronavirus disease 2019 (COVID-19), as well as a significantly increased long-term risk of cardiovascular diseases in COVID-19 survivors, have highlighted severe deficiencies in our understanding of thromboinflammation and the need for new therapeutic options. Due to the complexity of the immunothrombosis pathophysiology, the efficacy of treatment with conventional anti-thrombotic medication is questioned. Thrombolytics do appear efficacious, but are hindered by severe bleeding risks, limiting their use. Nanomedicine can have profound impact in this context, protecting delicate (bio)pharmaceuticals from degradation en route and enabling delivery in a targeted and on demand manner. We provide an overview of the most promising nanocarrier systems and design strategies that may be adapted to develop nanomedicine for COVID-19-induced thromboinflammation, including dual-therapeutic approaches with antiviral and immunosuppressants. Resultant targeted and side-effect-free treatment may aid greatly in the fight against the ongoing COVID-19 pandemic.
December 16, 2022
Bivalent booster doses provided additional protection against COVID-19–associated emergency department/urgent care encounters and hospitalizations in persons who previously received 2, 3, or 4 monovalent vaccine doses. Because of waning of monovalent vaccine-conferred immunity, relative effectiveness of bivalent vaccines was higher with increased time since the previous monovalent dose.
Among immunocompetent adults aged ≥65 years hospitalized in the multistate IVY Network, a bivalent booster dose provided 73% additional protection against COVID-19 hospitalization compared with past monovalent mRNA vaccination only.
This report summarizes the evidence and rationale supporting the components of the CSTE/CDC MIS-C surveillance case definition and describes the methods used to develop the definition. These methods included convening MIS-C clinical experts (i.e., consultants) regarding identification of MIS-C and its distinction from other pediatric conditions, a review of available literature comparing MIS-C phenotype with that of pediatric COVID-19 and other hyperinflammatory syndromes, and retrospective application of different criteria to data from MIS-C cases previously reported to CDC.
During the 2021–22 influenza season, 6% of hospitalized pediatric influenza patients had SARS-CoV-2 coinfection; a higher percentage of patients with coinfection required invasive or noninvasive respiratory support compared with those with influenza only. Among influenza-associated pediatric deaths, 16% had SARS-CoV-2 coinfection; only one coinfected decedent received influenza antivirals, and none had been fully vaccinated against influenza.
COVID-19 and Other Underlying Causes of Cancer Deaths — United States, January 2018–July 2022
Among persons who died with cancer, 2.0% in 2020 and 2.4% in 2021 had COVID-19 listed as the underlying cause of death, with higher percentages during COVID-19 peaks and among persons who were older, male, Hispanic or Latino, non-Hispanic American Indian or Alaska Native, non-Hispanic Black or African American, or living with leukemia, lymphoma, or myeloma.
December 15, 2022
The continued evolution of the SARS-CoV-2 Omicron variant has led to the emergence of numerous sublineages with different patterns of evasion from neutralizing antibodies. We investigated neutralizing activity in immune sera from individuals vaccinated with SARS-CoV-2 wild-type spike (S) glycoprotein-based COVID-19 mRNA vaccines after subsequent breakthrough infection with Omicron BA.1, BA.2, or BA.4/BA.5 to study antibody responses against sublineages of high relevance. We report that exposure of vaccinated individuals to infections with Omicron sublineages, and especially with BA.4/BA.5, results in a boost of Omicron BA.4.6, BF.7, BQ.1.1, and BA.2.75 neutralization, but does not efficiently boost neutralization of sublineages BA.2.75.2 and XBB. Accordingly, we found in in silico analyses that with occurrence of the Omicron lineage a large portion of neutralizing B-cell epitopes were lost, and that in Omicron BA.2.75.2 and XBB less than 12% of the wild-type strain epitopes are conserved. In contrast, HLA class I and class II presented T-cell epitopes in the S glycoprotein were highly conserved across the entire evolution of SARS-CoV-2 including Alpha, Beta, and Delta and Omicron sublineages, suggesting that CD8+ and CD4+ T-cell recognition of Omicron BQ.1.1, BA.2.75.2, and XBB may be largely intact. Our study suggests that while some Omicron sublineages effectively evade B-cell immunity by altering neutralizing antibody epitopes, S protein-specific T-cell immunity, due to the very nature of the polymorphic cell-mediated immune, response is likely to remain unimpacted and may continue to contribute to prevention or limitation of severe COVID-19 manifestation.
A Covid-19 Milestone Attained — A Correlate of Protection for Vaccines
The rapid identification of a correlate of protection (CoP) for Covid-19 vaccines — on the basis of several harmonized randomized phase 3 trials using common validated assays — constitutes an important success in vaccinology. A CoP is an immune marker that can be used to reliably predict a vaccine’s level of efficacy in preventing a clinically relevant outcome. The level of this marker is measured shortly (2 to 4 weeks) after completion of the vaccination regimen and provides an actionable basis for decisions such as regulatory approval of an efficacious vaccine for a new population that was not included in the pivotal randomized phase 3 trials, or approval of a refined version of a vaccine that was previously shown to be efficacious.
December 14, 2022
Missing data mean we’ll probably never know how many people died of COVID
This week in Nature1, researchers working with the World Health Organization (WHO) publish details of their calculations of excess mortality during the pandemic, after releasing their first figures earlier this year. The data suggest that during 2020 and 2021, excess mortality was some 2.7 times greater than the official toll, at between 13.2 million and 16.6 million deaths, with the most-likely value 14.8 million.
Subjective chemosensory dysfunction, as self-reported smell or taste deficiency, is highly predictive of serologic response following SARS-CoV-2 infection. This information may be useful for patient counseling. Additional longitudinal research should be performed to better understand the onset and duration of the serologic response in these patients.
SARS-CoV-2 infection and persistence in the human body and brain at autopsy
Coronavirus disease 2019 (COVID-19) is known to cause multi-organ dysfunction1,2,3 during acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients experiencing prolonged symptoms, termed post-acute sequelae of SARS-CoV-2 (refs. 4,5). However, the burden of infection outside the respiratory tract and time to viral clearance are not well characterized, particularly in the brain3,6,7,8,9,10,11,12,13,14. Here we carried out complete autopsies on 44 patients who died with COVID-19, with extensive sampling of the central nervous system in 11 of these patients, to map and quantify the distribution, replication and cell-type specificity of SARS-CoV-2 across the human body, including the brain, from acute infection to more than seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, predominantly among patients who died with severe COVID-19, and that virus replication is present in multiple respiratory and non-respiratory tissues, including the brain, early in infection. Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including throughout the brain, as late as 230 days following symptom onset in one case. Despite extensive distribution of SARS-CoV-2 RNA throughout the body, we observed little evidence of inflammation or direct viral cytopathology outside the respiratory tract. Our data indicate that in some patients SARS-CoV-2 can cause systemic infection and persist in the body for months.
Associations of Physical Inactivity and COVID-19 Outcomes Among Subgroups
Of 194,191 adults with COVID-19 infection, 6.3% were hospitalized, 3.1% experienced a deterioration event, and 2.8% died within 90 days. Dose‒response effects were strong; for example, patients in the some activity category had higher odds of hospitalization (OR=1.43; 95% CI=1.26, 1.63), deterioration (OR=1.83; 95% CI=1.49, 2.25), and death (OR=1.92; 95% CI=1.48, 2.49) than those in the always active category. Results were generally consistent across sex, race and ethnicity, age, and BMI categories and for patients with cardiovascular disease or hypertension.
The significantly lower rates of all-cause ED visits, hospitalizations, and mortality in the vaccinated highlight the real-world benefits of vaccination. The data raise questions about the wisdom of reliance on natural immunity when safe and effective vaccines are available.
December 13, 2022
Prognosis of Myocarditis Developing After mRNA COVID-19 Vaccination Compared With Viral Myocarditis
This study found a significantly lower rate of mortality among individuals with myocarditis after mRNA vaccination compared with those with viral infection–related myocarditis. Prognosis of this iatrogenic condition may be less severe than naturally acquired viral infection–related myocarditis.
Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants
The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against BQ and XBB subvariants were lower by 13-81-fold and 66-155-fold, respectively, far beyond what had been observed to date. Monoclonal antibodies capable of neutralizing the original Omicron variant were largely inactive against these new subvariants, and the responsible individual spike mutations were identified. These subvariants were found to have similar ACE2-binding affinities as their predecessors. Together, our findings indicate that BQ and XBB subvariants present serious threats to current COVID-19 vaccines, render inactive all authorized antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.
Nirmatrelvir Plus Ritonavir for Early COVID-19 in a Large U.S. Health System
During the study period, 12 541 (28.1%) patients were prescribed nirmatrelvir plus ritonavir, and 32 010 (71.9%) were not. Patients prescribed nirmatrelvir plus ritonavir were more likely to be older, have more comorbidities, and be vaccinated. The composite outcome of hospitalization or death occurred in 69 (0.55%) patients who were prescribed nirmatrelvir plus ritonavir and 310 (0.97%) who were not (adjusted risk ratio, 0.56 [95% CI, 0.42 to 0.75]). Recipients of nirmatrelvir plus ritonavir had lower risk for hospitalization (adjusted risk ratio, 0.60 [CI, 0.44 to 0.81]) and death (adjusted risk ratio, 0.29 [CI, 0.12 to 0.71]).
December 12, 2022
Postural orthostatic tachycardia syndrome (POTS) was previously described after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, limited data are available on the relation of POTS with Coronavirus Disease 2019 (COVID-19) vaccination. Here we show, in a cohort of 284,592 COVID-19-vaccinated individuals, using a sequence–symmetry analysis, that the odds of POTS are higher 90 days after vaccine exposure than 90 days before exposure; we also show that the odds for POTS are higher than referent conventional primary care diagnoses but lower than the odds of new POTS diagnosis after SARS-CoV-2 infection. Our results identify a possible association between COVID-19 vaccination and incidence of POTS. Notwithstanding the probable low incidence of POTS after COVID-19 vaccination, particularly when compared to SARS-Cov-2 post-infection odds, which were five times higher, our results suggest that further studies are needed to investigate the incidence and etiology of POTS occurring after COVID-19 vaccination.
The risks of POTS after COVID-19 vaccination and SARS-CoV-2 infection: it’s worth a shot
The study is based on a large series of approximately 300,000 vaccinated individuals from one geographic territory in the USA (Los Angeles County), with 0.27% new post-vaccination POTS diagnoses compared with 0.18% in the pre-vaccination period, giving an odds ratio of 1.52 for post-vaccination POTS diagnoses. Accumulating all POTS-associated diagnoses in one group gave slightly lower odds. Interestingly, among 12,460 individuals with confirmed SARS-CoV-2 infection, the pre-infection incidence of POTS was 1.73%, compared with 3.42% after infection. This suggests that those with symptomatic COVID-19 infection were more likely to develop POTS in general, and that the risk of post-infection POTS is much higher than post-vaccination POTS in this cohort.
Although ocular manifestations are reported in patients with COVID-19, consensus on ocular tropism of SARS-CoV-2 is lacking. Here, we infect K18-hACE2 transgenic mice with SARS-CoV-2 using various routes. We observe ocular manifestation and retinal inflammation with production of pro-inflammatory cytokines in the eyes of intranasally (IN)-infected mice. Intratracheal (IT) infection results in dissemination of the virus from the lungs to the brain and eyes via trigeminal and optic nerves. Ocular and neuronal invasions are confirmed using intracerebral (IC) infection. Notably, the eye-dropped (ED) virus does not cause lung infection and becomes undetectable with time. Ocular and neurotropic distribution of the virus in vivo is evident in fluorescence imaging with an infectious clone of SARS-CoV-2-mCherry. The ocular tropic and neuroinvasive characteristics of SARS-CoV-2 are confirmed in wild-type Syrian hamsters. Our data can improve the understanding regarding viral transmission and clinical characteristics of SARS-CoV-2 and help in improving COVID-19 control procedures.
December 11, 2022
The human immunoglobulin heavy chain (IGH) locus is exceptionally polymorphic, with high levels of allelic and structural variation. Thus, germline IGH genotypes are personal, which may influence responses to infection and vaccination. For an improved understanding of inter-individual differences in antibody responses, we isolated SARS-CoV-2 spike-specific monoclonal antibodies from convalescent health care workers, focusing on the IGHV1-69 gene, which has the highest level of allelic variation of all IGHV genes. The IGHV1-69∗20-using CAB-I47 antibody and two similar antibodies isolated from an independent donor were critically dependent on allele usage. Neutralization was retained when reverting the V region to the germline IGHV1-69∗20 allele but lost when reverting to other IGHV1-69 alleles. Structural data confirmed that two germline-encoded polymorphisms, R50 and F55, in the IGHV1-69 gene were required for high affinity receptor binding domain interaction. These results demonstrate that single polymorphisms in IGH genes can influence the function of SARS-CoV-2 neutralizing antibodies.
December 9, 2022
Tissue-resident memory T (TRM) cells were originally identified as a tissue-sequestered population of memory T cells that show lifelong persistence in non-lymphoid organs. That definition has slowly evolved with the documentation of TRM cells having variable terms of tissue residency combined with a capacity to return to the wider circulation. Nonetheless, reductionist experiments have identified an archetypical population of TRM cells showing intrinsic permanent residency in a wide range of non-lymphoid organs, with one notable exception: the lungs. Despite the fact that memory T cells generated during a respiratory infection are maintained in the circulation, local TRM cell numbers in the lung decline concomitantly with a decay in T cell-mediated protection. This Perspective describes the mechanisms that underpin long-term T cell lodgement in non-lymphoid tissues and explains why residency is transient for select TRM cell subsets. In doing so, it highlights the unusual nature of memory T cell egress from the lungs and speculates on the broader disease implications of this process, especially during infection with SARS-CoV-2.
Persistently elevated SARS-CoV-2 antibody in plasma may not indicate persistence of antibody at mucosal sites such as the nose. The strong correlation of SARS-CoV-2 antibody in the nose and saliva with that in the blood suggests that mucosal antibodies are derived primarily from transudation from the blood rather than local production. While SARS-CoV-2 vaccine given peripherally boosted mucosal immune responses in infected persons, the increase in antibody titers were higher in the plasma than at mucosal sites. Taken together, these observations indicate the need for development of mucosal vaccines to induce potent immune responses at sites where SARS-CoV-2 infection occurs.
December 8, 2022
Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae
Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are debilitating, clinically heterogeneous and of unknown molecular etiology. A transcriptome-wide investigation was performed in 165 acutely infected hospitalized individuals who were followed clinically into the post-acute period. Distinct gene expression signatures of post-acute sequelae were already present in whole blood during acute infection, with innate and adaptive immune cells implicated in different symptoms. Two clusters of sequelae exhibited divergent plasma-cell-associated gene expression patterns. In one cluster, sequelae associated with higher expression of immunoglobulin-related genes in an anti-spike antibody titer-dependent manner. In the other, sequelae associated independently of these titers with lower expression of immunoglobulin-related genes, indicating lower non-specific antibody production in individuals with these sequelae. This relationship between lower total immunoglobulins and sequelae was validated in an external cohort. Altogether, multiple etiologies of post-acute sequelae were already detectable during SARS-CoV-2 infection, directly linking these sequelae with the acute host response to the virus and providing early insights into their development.
December 7, 2022
The Omicron era of the COVID-19 pandemic commenced at the beginning of 2022 and whilst it started with primarily BA.1, it was latter dominated by BA.2 and related sub-lineages. Over the course of 2022, we monitored the potency and breadth of antibody neutralization responses to many emerging variants at two levels: (i) we tracked over 400,000 U.S. plasma donors over time through various vaccine booster roll outs and Omicron waves using sequentially collected IgG pools; (ii) we mapped the antibody response in individuals using blood from strigently curated vaccine and convalescent cohorts. In pooled IgG samples, we observed the maturation of neutralization breadth to Omicron variants over time through continuing vaccine and infection waves. Importantly, in many cases we observed increased antibody breadth to variants that were yet to be in circulation. Determination of viral neutralization at the cohort level supported equivalent coverage across prior and emerging variants with emerging isolates BQ.1.1, XBB.1 and BR.2.1 the most evasive. Further, these emerging variants were resistant to Evusheld, whilst neutralization resistance to Sotrovimab was restricted to BQ.1.1 and this was further supported by lack of antibody binding to this variant. An outgrowth advantage which correlated with better utilization of TMPRSS2 was observed across BQ lineages but not those derived from BA.2.75. We conclude at this current point in time that variants derived from BQ lineages can evade antibodies at levels equivalent to their most evasive BA.2.75 counterparts but sustain an entry phenotype that would promote an additional outgrowth advantage.
December 6, 2022
We assessed the neutralisation of XBB.1 and XBB.3 compared with BA.5.2 (a widely circulating strain since July, 2022) and the ancestral strain, using a live virus neutralisation test. XBB.1 differs from XBB.3 due to an extra spike mutation: Gly252Val. We included sera specimens from 30 individuals who received two to four doses of BNT16b2 (Pfizer-BioNtech) or CoronaVac with or without previous SARS-CoV-2 infection (seven [23%] individuals who received two vaccinations and had a previous BA.2 infection; seven [23%] who received three vaccinations and had a previous BA.2 infection; nine [30%] who received three vaccinations and had no previous SARS-CoV-2 infections; and seven [23%] who received four vaccinations and had no previous SARS-CoV-2 infections; appendix p 3). Overall, the geometric mean 50% neutralising antibody titre (NT50 GMT) was lower for XBB strains (XBB.1, 26.0; XBB.3, 19.4) than the ancestral strain (436.1; XBB.1 16·8-fold, p<0.0001; XBB.3: 22·5-fold, p<0·0001) or BA.5.2 strain (87.4; XBB.1 3·4-fold, p=0·0191; XBB.3 4·5-fold, p<0·0001), but the difference between XBB.1 and XBB.3 was not statistically significant (p=0·17; appendix p 1). All subgroups with different history of vaccination or infection had a statistically significantly lower GMT against XBB.1 or XBB.3 than those against the ancestral strain (appendix p 1).
The newly emerged SARS-CoV-2 Omicron sublineages, including the BA.2-derived BA.2.75.2 and the BA.5-derived BQ.1.1 and XBB.1, have accumulated additional spike mutations that may affect vaccine effectiveness. Here we report neutralizing activities of three human serum panels collected from individuals 23–94 days after dose 4 of a parental mRNA vaccine, 14–32 days after a BA.5-bivalent-booster from individuals with 2–4 previous doses of parental mRNA vaccine, or 15–32 days after a BA.5-bivalent-booster from individuals with previous SARS-CoV-2 infection and 2–4 doses of parental mRNA vaccine. The results showed that a BA.5-bivalent-booster elicited a high neutralizing titer against BA.4/5 measured at 14- to 32-day post-boost; however, the BA.5-bivalent-booster did not produce robust neutralization against the newly emerged BA.2.75.2, BQ.1.1, or XBB.1. Previous infection significantly enhanced the magnitude and breadth of BA.5-bivalent-booster-elicited neutralization. Our data support a vaccine update strategy that future boosters should match newly emerged circulating SARS-CoV-2 variants.
Incidence of Viral Rebound After Treatment With Nirmatrelvir-Ritonavir and Molnupiravir
In this cohort study of 12 629 adults in Hong Kong with COVID-19 who were hospitalized and had serial cycle threshold values measured, viral rebound (defined as a cycle threshold value >40 that decreased to ≤40) occurred in 68 antiviral nonusers (0.6%), 2 (1.0%) nirmatrelvir-ritonavir users, and 6 (0.8%) molnupiravir users. In this study, viral rebound was uncommon in adults with COVID-19 after treatment with nirmatrelvir-ritonavir and molnupiravir, suggesting that these novel oral antivirals should be prescribed to more patients with COVID-19 in the early phase of the infection.
December 5, 2022
Multiscale landscaping of droplet wettability on fibrous layers of facial masks
Unlike large droplets, microdroplets interact sensitively with the fibers they contact and are prone to evaporation in facial mask applications, while data for droplet sizes from the previous test regime skewed even after the worldwide spread of COVID-19. Herein, we present the wettability characteristics of fibrous layers, which reveal a multiscale landscape of droplet wettability from the millimeter to the micrometer scales to improve the understanding of dynamic wetting behaviors of infectious droplets on fibrous media.
Effect of hybrid immunity and bivalent booster vaccination on omicron sublineage neutralisation
Collectively, our results show that the emerging omicron sublineages BQ.1.1 and particularly BA.2.75.2 efficiently evade neutralisation independent of the immunisation history. Although monovalent and bivalent vaccine boosters both induce high neutralising activity and increase neutralisation breadth, BA.2.75.2-specific and BQ.1.1-specific neutralisation activity remained relatively low. This finding is in keeping with the concept of immune imprinting by initial immunisation with vaccines targeting the ancestral SARS-CoV-2 B.1 lineage. Furthermore, the observation that neutralisation of BA.2.75.2pp and BQ.1.1pp was most efficient in the cohort that had a breakthrough infection during the BA.1 and BA.2 wave and later received a bivalent booster vaccination, but was still less efficient than neutralisation of B.1pp, implies that affinity maturation of antibodies and two-time stimulation with different omicron antigens might still not be sufficient to overcome immune imprinting. As a consequence, novel vaccination strategies have to be developed to overcome immune imprinting by ancestral SARS-CoV-2 antigen.
In late 2022, although the SARS-CoV-2 Omicron subvariants have highly diversified, some lineages have convergently acquired amino acid substitutions at five critical residues in the spike protein. Here, we illuminated the evolutionary rules underlying the convergent evolution of Omicron subvariants and the properties of one of the latest lineages of concern, BQ.1.1. Our phylogenetic and epidemic dynamics analyses suggest that Omicron subvariants independently increased their viral fitness by acquiring the convergent substitutions. Particularly, BQ.1.1, which harbors all five convergent substitutions, shows the highest fitness among the viruses investigated. Neutralization assays show that BQ.1.1 is more resistant to breakthrough BA.2/5 infection sera than BA.5. The BQ.1.1 spike exhibits enhanced binding affinity to human ACE2 receptor and greater fusogenicity than the BA.5 spike. However, the pathogenicity of BQ.1.1 in hamsters is comparable to or even lower than that of BA.5. Our multiscale investigations provide insights into the evolutionary trajectory of Omicron subvariants.
We did not observe a higher risk of a first time diagnosis of type 1 diabetes in children 30 days or more after a positive SARS-CoV-2 test, compared to children with a history of only negative SARS-CoV-2 tests (Hazard ratio 0.85, 95% CI 0.70, 1.04).
Severe COVID-19 is associated with molecular signatures of aging in the human brain
As coronavirus disease 2019 (COVID-19) and aging are both accompanied by cognitive decline, we hypothesized that COVID-19 might lead to molecular signatures similar to aging. We performed whole-transcriptome analysis of the frontal cortex, a critical area for cognitive function, in individuals with COVID-19, age-matched and sex-matched uninfected controls, and uninfected individuals with intensive care unit/ventilator treatment. Our findings indicate that COVID-19 is associated with molecular signatures of brain aging and emphasize the value of neurological follow-up in recovered individuals.
Myopericarditis After COVID-19 mRNA Vaccination Among Adolescents and Young Adults
In this systematic review and meta-analysis of 23 studies, including 854 patients aged 12 to 20 years with vaccine-associated myopericarditis, the incidence of myopericarditis was higher in males after the second dose. Although 15.6% of patients had left ventricular (LV) systolic dysfunction, only 1.3% had severe LV systolic dysfunction (ejection fraction <35%); late gadolinium enhancement was found in 87.2% and 23.2% required intensive care unit admission; however, no in-hospital mortality was observed. These findings suggest largely favorable outcomes of COVID-19 vaccine-associated myopericarditis in adolescents and young adults.
December 3, 2022
Ratios of the change in seroprevalence to the change in case prevalence suggest a high proportion of infections were not detected by case-based surveillance during periods of increased transmission. The largest increases in the seroprevalence to case prevalence ratios coincided with the spread of the B.1.1.529 (Omicron) variant and with increased accessibility of home testing. Ratios varied by region and season with the highest ratios in the midwestern and southern United States during winter 2021–2022. Our results demonstrate that reported case counts did not fully capture differing underlying infection rates and demonstrate the value of sero-surveillance in understanding the full burden of infection. Levels of infection-induced antibody seroprevalence, particularly spikes during periods of increased transmission, are important to contextualize vaccine effectiveness data as the susceptibility to infection of the U.S. population changes.
December 2, 2022
Post-exertional symptom exacerbation (PESE) is a characteristic symptom of post-COVID syndrome (PCS). This prospective study investigated the effect of a 6-week structured World Health Organization (WHO) Borg CR-10 5-phase pacing protocol on PESE episodes and quality of life in a cohort of individuals with long-standing PCS (average duration of symptoms was 17 months). Participants received weekly telephone calls with a clinician to complete the Leeds PESE questionnaire (LPQ) and identify the appropriate phase of the pacing protocol. EQ-5D 5L was completed at the intervention's beginning and end to measure overall health. Thirty-one participants completed the 6-week protocol, with a statistically and clinically significant reduction in the average number of PESE episodes (from 3.4 episodes in Week 1 to 1.1 in Week 6), with an average decrease of 16% (95% CI: 9%−24%; p < 0.001) each week, and reduction across all three exertional triggers (physical, cognitive, and emotional). Physical activity levels showed moderate improvements during the intervention period. Mean EQ-5D 5L scores improved from 51.4 to 60.6 points (paired difference of 9.2 points, 95% CI: 3.2−15.2 points; p = 0.004). A structured pacing protocol significantly reduces PESE episodes and improves overall health in PCS.
During August 2021–May 2022, 41.6% of a convenience sample of adults had both anti-spike antibodies (indicating previous infection or vaccination) and anti-nucleocapsid antibodies (indicating previous infection only); 43.7% of these persons were possibly asymptomatically infected. Prevalence of serologic patterns consistent with vaccination without infection was lower among adults who were younger, Hispanic and non-Hispanic Black or African American adults, and persons with less education.
Respiratory tract resident memory T cells (TRM), typically generated by local vaccination or infection, can accelerate control of pulmonary infections that evade neutralizing antibody. It is unknown whether mRNA vaccination establishes respiratory TRM. We generated a self-amplifying mRNA vaccine encoding the influenza A virus nucleoprotein that is encapsulated in modified dendron–based nanoparticles. Here, we report how routes of immunization in mice, including contralateral versus ipsilateral intramuscular boosts, or intravenous and intranasal routes, influenced influenza-specific cell–mediated and humoral immunity. Parabiotic surgeries revealed that intramuscular immunization was sufficient to establish CD8 TRM in the lung and draining lymph nodes. Contralateral, compared with ipsilateral, intramuscular boosting broadened the distribution of lymph node TRM and T follicular helper cells but slightly diminished resulting levels of serum antibody. Intranasal mRNA delivery established modest circulating CD8 and CD4 T cell memory but augmented distribution to the respiratory mucosa. Combining intramuscular immunizations with an intranasal mRNA boost achieved high levels of both circulating T cell memory and lung TRM. Thus, routes of mRNA vaccination influence humoral and cell-mediated immunity, and intramuscular prime-boosting establishes lung TRM that can be further expanded by an additional intranasal immunization.
SARS-CoV-2 viral load and shedding kinetics
SARS-CoV-2 viral load and detection of infectious virus in the respiratory tract are the two key parameters for estimating infectiousness. As shedding of infectious virus is required for onward transmission, understanding shedding characteristics is relevant for public health interventions. Viral shedding is influenced by biological characteristics of the virus, host factors and pre-existing immunity (previous infection or vaccination) of the infected individual. Although the process of human-to-human transmission is multifactorial, viral load substantially contributed to human-to-human transmission, with higher viral load posing a greater risk for onward transmission. Emerging SARS-CoV-2 variants of concern have further complicated the picture of virus shedding. As underlying immunity in the population through previous infection, vaccination or a combination of both has rapidly increased on a global scale after almost 3 years of the pandemic, viral shedding patterns have become more distinct from those of ancestral SARS-CoV-2. Understanding the factors and mechanisms that influence infectious virus shedding and the period during which individuals infected with SARS-CoV-2 are contagious is crucial to guide public health measures and limit transmission. Furthermore, diagnostic tools to demonstrate the presence of infectious virus from routine diagnostic specimens are needed.
December 1, 2022
Mutations in SARS-CoV-2 spike protein impair epitope-specific CD4+ T cell recognition
CD4+ T cells are essential for protection against viruses, including SARS-CoV-2. The sensitivity of CD4+ T cells to mutations in SARS-CoV-2 variants of concern (VOCs) is poorly understood. Here, we isolated 159 SARS-CoV-2-specific CD4+ T cell clones from healthcare workers previously infected with wild-type SARS-CoV-2 (D614G) and defined 21 epitopes in spike, membrane and nucleoprotein. Lack of CD4+ T cell cross-reactivity between SARS-CoV-2 and endemic beta-coronaviruses suggested these responses arose from naïve rather than pre-existing cross-reactive coronavirus-specific T cells. Of the 17 epitopes located in the spike protein, 10 were mutated in VOCs and CD4+ T cell clone recognition of 7 of them was impaired, including 3 of the 4 epitopes mutated in omicron. Our results indicated that broad targeting of epitopes by CD4+ T cells likely limits evasion by current VOCs. However, continued genomic surveillance is vital to identify new mutations able to evade CD4+ T cell immunity.
Data-driven identification of post-acute SARS-CoV-2 infection subphenotypes
The post-acute sequelae of SARS-CoV-2 infection (PASC) refers to a broad spectrum of symptoms and signs that are persistent, exacerbated or newly incident in the period after acute SARS-CoV-2 infection. Most studies have examined these conditions individually without providing evidence on co-occurring conditions. In this study, we leveraged the electronic health record data of two large cohorts, INSIGHT and OneFlorida+, from the national Patient-Centered Clinical Research Network. We created a development cohort from INSIGHT and a validation cohort from OneFlorida+ including 20,881 and 13,724 patients, respectively, who were SARS-CoV-2 infected, and we investigated their newly incident diagnoses 30–180 days after a documented SARS-CoV-2 infection. Through machine learning analysis of over 137 symptoms and conditions, we identified four reproducible PASC subphenotypes, dominated by cardiac and renal (including 33.75% and 25.43% of the patients in the development and validation cohorts); respiratory, sleep and anxiety (32.75% and 38.48%); musculoskeletal and nervous system (23.37% and 23.35%); and digestive and respiratory system (10.14% and 12.74%) sequelae. These subphenotypes were associated with distinct patient demographics, underlying conditions before SARS-CoV-2 infection and acute infection phase severity. Our study provides insights into the heterogeneity of PASC and may inform stratified decision-making in the management of PASC conditions.
Effect of air pollution on the human immune system
Our study shows that pollutants in our environment have a direct and detrimental effect on the human immune system, and specifically the immune organs that are associated with the respiratory tract. LNs filter impurities and coordinate the clearance of harmful antigens and pathogens, but over decades the LNs connected to the lungs become clogged with particulates, and as a result they are not able to carry out essential functions of host defense and immune surveillance. In addition, the effects of pollutants are cumulative and can in part account for the worse outcome of respiratory infections in elderly individuals compared with younger populations.
November 30, 2022
Results: Dyspnea on exertion was the leading symptom of pulmonary PASC in our cohort. In 16% and 42.9% of patients, FEV1 and MEF50 were ≤80% and 35.3% showed low attenuation volume (LAV) in >5% of lung area, in line with airflow obstruction. There was a significant correlation between oxygen pulse and time since COVID (p=0.009). Histopathologically, PASC manifested as organizing pneumonia (OP), fibrinous alveolitis and increased CD4+ T cell infiltrate predominantly around airways (bronchiolitis), while the residual virus components were detectable in only a single PASC patient (2%). T cell infiltrates around small airways were inversely correlated with time since COVID, however, this trend failed to reach statistical significance. We identified discrete interstitial fibrosis and a pro-fibrotic macrophage subtype (CD68/CD163/S100A9) as well as significantly elevated interleukin 1β in BAL fluid from PASC patients (p=0.01), but H-scores for fibrotic macrophage population did not correlate with severity of clinical symptoms or T cell infiltration. Interpretation: We show decreased FEV1/MEF50 and increased LAV in line with obstructive lung disease due to CD4+ T cell-predominant bronchiolitis as well as evidence of pro-fibrotic signaling in a subset of unvaccinated PASC patients. Since our results point towards self-limiting inflammation of small airways without detectable viral reservoirs, it remains unclear whether pulmonary symptoms in PASC are SARS-CoV-2-specific or represent a general response to viral infection. Still, evidence of pro-fibrotic signaling should warrant clincal follow-up and further research into possible long-time fibrotic remodeling in PASC patients.
Vaccine effectiveness in preventing mortality remained high in children and adolescents regardless of the circulating variant. Vaccine effectiveness in preventing SARS-CoV-2 infection in the short term after vaccination was lower during omicron predominance and decreasing sharply over time.
November 29, 2022
Post-COVID syndrome remains poorly studied in children and adolescents. Here, we aimed to investigate the prevalence and risk factors of pediatric post-COVID in a population-based sample, stratifying by serological status. Children from the SEROCoV-KIDS cohort study (State of Geneva, Switzerland), aged 6 months to 17 years, were tested for anti-SARS-CoV-2 N antibodies (December 2021-February 2022) and parents filled in a questionnaire on persistent symptoms in their children (lasting over 12 weeks) compatible with post-COVID. Of 1034 children tested, 570 (55.1%) were seropositive. The sex- and age-adjusted prevalence of persistent symptoms among seropositive children was 9.1% (95%CI: 6.7;11.8) and 5.0% (95%CI: 3.0;7.1) among seronegatives, with an adjusted prevalence difference (ΔaPrev) of 4.1% (95%CI: 1.1;7.3). Stratifying per age group, only adolescents displayed a substantial risk of having post-COVID symptoms (ΔaPrev = 8.3%, 95%CI: 3.5;13.5). Identified risk factors for post-COVID syndrome were older age, having a lower socioeconomic status and suffering from chronic health conditions, especially asthma. Our findings show that a significant proportion of seropositive children, particularly adolescents, experienced persistent COVID symptoms. While there is a need for further investigations, growing evidence of pediatric post-COVID urges early screening and primary care management.
In conclusion, a shift in COVID-19 mortality to relatively younger people in the second pandemic year contributed to markedly elevated YLL from this increasingly preventable cause of death.
November 28, 2022
Immune signature atlas of vaccines: learning from the good responders
Understanding immune determinants of vaccine-mediated immunogenicity could further provide rational vaccine design. Two research groups revealed pre-existing and early innate immune signatures associated with better vaccine-mediated antibody responses.
Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants
The SARS-CoV-2 Omicron variant continues to evolve, with new BQ and XBB subvariants now rapidly expanding in Europe/US and Asia, respectively. As these new subvariants have additional spike mutations, they may possess altered antibody evasion properties. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals who were boosted with a WA1/BA.5 bivalent mRNA vaccine. Compared to the ancestral strain D614G, serum neutralizing titers against BQ and XBB subvariants were lower by 13-81-fold and 66-155-fold, respectively, far beyond what had been observed to date. A panel of monoclonal antibodies capable of neutralizing the original Omicron variant, including those with Emergency Use Authorization, were largely inactive against these new subvariants. The spike mutations that conferred antibody resistance were individually studied and structurally explained. Finally, the ACE2-binding affinities of the spike proteins of these novel subvariants were found to be similar to those of their predecessors. Taken together, our findings indicate that BQ and XBB subvariants present serious threats to the efficacy of current COVID-19 vaccines, render inactive all authorized monoclonal antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.
Alterations of the fecal microbiota in relation to acute COVID-19 infection and recovery
People with acute COVID-19 due to SARS-CoV-2 infection experience a range of symptoms, but major factors contributing to severe clinical outcomes remain to be understood. Emerging evidence suggests associations between the gut microbiome and the severity and progression of COVID-19. To better understand the host-microbiota interactions in acute COVID-19, we characterized the intestinal microbiome of patients with active SARS-CoV-2 infection in comparison to recovered patients and uninfected healthy controls. We performed 16S rRNA sequencing of stool samples collected between May 2020 and January 2021 from 20 COVID-19-positive patients, 20 COVID-19-recovered subjects and 20 healthy controls. COVID-19-positive patients had altered microbiome community characteristics compared to the recovered and control subjects, as assessed by both α- and β-diversity differences. In COVID-19-positive patients, we observed depletion of Bacteroidaceae, Ruminococcaceae, and Lachnospiraceae, as well as decreased relative abundances of the genera Faecalibacterium, Adlercreutzia, and the Eubacterium brachy group. The enrichment of Prevotellaceae with COVID-19 infection continued after viral clearance; antibiotic use induced further gut microbiota perturbations in COVID-19-positive patients. In conclusion, we present evidence that acute COVID-19 induces gut microbiota dysbiosis with depletion of particular populations of commensal bacteria, a phenomenon heightened by antibiotic exposure, but the general effects do not persist post-recovery.
November 25, 2022
Electron microscopy and immunohistochemical staining showed SARS CoV-2 virus in the penile corpus cavernosum of patients 1 month after COVID-19 recovery. Immunohistochemical staining intensity correlated with the severity of previous infection. Transmission electron microscopy revealed intracellular virtual particles of about 80 nm with a typical morphology of prominent spikes and electron-dense dots of nucleocapsid in addition to vesicles filled with virus-like particles. Cells showed increased membrane trafficking. The 1 month after COVID-19 group showed an increased number of fibroblasts. The 7 months after COVID-19 group had similar morphology and immunoreactivity as control group.
November 24, 2022
Endosomes, receptors, and viruses
Viral infection is facilitated by the molecular recognition of specific receptors and host factors at the plasma membrane, which provides a gateway into host cells (1). These factors act as “locks” that control access to the intracellular environment, to which viruses have evolved cognate molecular “keys” to gain entry and replicate. In the evolutionary arms race between viruses and their hosts, the development of effective antiviral therapeutic strategies to inhibit this process poses a crucial public health challenge, recently emphasized by the COVID-19 pandemic.
November 23, 2022
Molecular and cellular similarities in the brain of SARS-CoV-2 and Alzheimer’s disease individuals
Infection with the etiological agent of COVID-19, SARS-CoV-2, appears capable of impacting cognition, which some patients with Post-acute Sequelae of SARS-CoV-2 (PASC). To evaluate neuro-pathophysiological consequences of SARS-CoV-2 infection, we examine transcriptional and cellular signatures in the Broadman area 9 (BA9) of the frontal cortex and the hippocampal formation (HF) in SARS-CoV-2, Alzheimers disease (AD) and SARS-CoV-2 infected AD individuals, compared to age- and gender-matched neurological cases. Here we show similar alterations of neuroinflammation and blood-brain barrier integrity in SARS-CoV-2, AD, and SARS-CoV-2 infected AD individuals. Distribution of microglial changes reflected by the increase of Iba-1 reveal nodular morphological alterations in SARS-CoV-2 infected AD individuals. Similarly, HIF-1α is significantly upregulated in the context of SARS-CoV-2 infection in the same brain regions regardless of AD status. The finding may help to inform decision-making regarding therapeutic treatments in patients with neuro-PASC, especially those at increased risk of developing AD.
Association of COVID-19 with diabetes: a systematic review and meta-analysis
Emerging evidence suggests that coronavirus disease-2019 (COVID-19) may lead to a wide range of post-acute sequelae outcomes, including new onset of diabetes. The aim of this meta-analysis was to estimate the incidence of newly diagnosed diabetes in survivors of COVID-19. We searched MEDLINE, Scopus, Cochrane Central Register of Controlled Trials and the World Health Organization Global Literature on Coronavirus Disease and clinical trial registries for studies reporting the association of COVID-19 and diabetes. Search dates were December 2019–October 16, 2022. Two investigators independently assessed studies for inclusion. Risk of bias was assessed using the Newcastle–Ottawa Scale. We estimated the effect of COVID-19 on incident diabetes by random-effects meta-analyses using the generic inverse variance method. We identified 8 eligible studies consisting of 4,270,747 COVID-19 patients and 43,203,759 controls. Median age was 43 years (interquartile range, IQR 35–49), and 50% were female. COVID-19 was associated with a 66% higher risk of incident diabetes (risk ratio, 1.66; 95% CI 1.38; 2.00). The risk was not modified by age, sex, or study quality. The median risk of bias assessment was 7. In this systematic review and meta-analysis, COVID-19 was associated with higher risk for developing new onset diabetes among survivors. Active monitoring of glucose dysregulation after recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is warranted.
November 22, 2022
In this study of vaccine effectiveness of the U.S.-authorized bivalent mRNA booster formulations, bivalent boosters provided significant additional protection against symptomatic SARS-CoV-2 infection in persons who had previously received 2, 3, or 4 monovalent vaccine doses. Due to waning immunity of monovalent doses, the benefit of the bivalent booster increased with time since receipt of the most recent monovalent vaccine dose.
Among U.S. adults diagnosed with COVID-19, including those with previous infection or vaccination, persons who were prescribed Paxlovid within 5 days of diagnosis had a 51% lower hospitalization rate within 30 days after diagnosis than those who were not prescribed Paxlovid.
November 21, 2022
Although absolute rates of myocarditis were low, vaccine type, age and sex are important factors to consider when strategizing vaccine administration to reduce the risk of postvaccination myocarditis. Our findings support the preferential use of the BNT162b2 vaccine over the mRNA-1273 vaccine for people aged 18–29 years.
November 20, 2022
Importance: While a substantial fraction of the US population was infected with SARS-CoV-2 during December 2021-February 2022, the subsequent evolution of population immunity against SARS-CoV-2 Omicron variants reflects the competing influences of waning protection over time and acquisition or restoration of immunity through additional infections and vaccinations. Objective: To estimate changes in population immunity against infection and severe disease due to circulating SARS-CoV-2 Omicron variants in the United States from December 2021 to October 2022, and to quantify the protection against a potential 2022-2023 winter SARS-CoV-2 wave. Design, setting, participants: Bayesian evidence synthesis of reported COVID-19 data (diagnoses, hospitalizations), vaccinations, and waning patterns for vaccine- and infection-acquired immunity, using a mathematical model of COVID-19 natural history. Main Outcomes and Measures: Population immunity against infection and severe disease from SARS-CoV-2 Omicron variants in the United States, by location (national, state, county) and week. Results: By November 10, 2022, 94% (95% CrI, 79%-99%) of the US population were estimated to have been infected by SARS-CoV-2 at least once. Combined with vaccination, 97% (95%-99%) were estimated to have some prior immunological exposure to SARS-CoV-2. Between December 1, 2021 and November 10, 2022, protection against a new Omicron infection rose from 22% (21%-23%) to 63% (51%-75%) nationally, and protection against an Omicron infection leading to severe disease increased from 61% (59%-64%) to 89% (83%-92%). Increasing first booster uptake to 55% in all states (current US coverage: 34%) and second booster uptake to 22% (current US coverage: 11%) would increase protection against infection by 4.5 percentage points (2.4-7.2) and protection against severe disease by 1.1 percentage points (1.0-1.5). Conclusions and Relevance: Effective protection against SARS-CoV-2 infection and severe disease in October 2022 was substantially higher than in December 2021. Despite this high level of protection, a more transmissible or immune evading (sub)variant, changes in behavior, or ongoing waning of immunity could lead to a new SARS-CoV-2 wave.
Background The emergence of SARS-CoV-2 variants has significantly reduced the efficacy of some approved vaccines. A fourth dose of NVX-CoV2373 (5μg SARS-CoV-2 rS + 50μg Matrix-M™ adjuvant) was evaluated to determine induction of cross-reactive antibodies to variants of concern. Methods A phase 2 randomized study assessed a fourth dose of NVX-CoV2373 in adults 18-84 years of age (2-dose primary series followed by third and fourth doses at 6-month intervals). Local/systemic reactogenicity was assessed the day of vaccination and for 6 days thereafter. Unsolicited adverse events (AEs) were reported. Immunogenicity was measured before, and 14 days after, fourth dose administration using anti-spike neutralization assays against the ancestral SARS-CoV-2 strain and Omicron sublineages. Antigenic cartography assessed antigenic distances between ancestral and variant strains. Results Among 1283 enrolled participants, 258 were randomized to receive the 2-dose primary series, of whom 104 received a third dose, and 45 received a fourth dose of NVX-CoV2373. The incidence of local/systemic reactogenicity events increased after the first three doses of NVX-CoV2373, and leveled off after dose four. Unsolicited AEs were reported in 9% of participants after dose 4 (none severe or serious). Neutralization antibody titers increased following booster doses. Antigenic cartography demonstrated reductions in antigenic distance between ancestral and variant SARS-CoV-2 strains with increased number of NVX-CoV2373 doses. Conclusions A fourth dose of NVX-CoV2373 enhanced immunogenicity without increasing reactogenicity. Antigenic cartography demonstrated a more universal-like response against SARS-CoV-2 variants after a fourth dose of NVX-CoV2373, indicating that updates to the vaccine composition may not be warranted. Trial registration number: NCT04368988
November 19, 2022
Offline: COVID-19—the lessons that science forgot
Remember the pandemic? Barely. Economist Impact, a policy research team within The Economist Group, supported by The Lancet's publisher Elsevier, last week launched Confidence in Research—a report exploring attitudes of scientists to the practice and communication of science during the pandemic. Based on a survey of over 3000 researchers worldwide, Economist Impact identified important actions that should be considered if mistakes are not to be repeated during future health emergencies.
November 18, 2022
One half of adults surveyed during June–July 2022 who had recently received a positive SARS-CoV-2 test result in metropolitan Detroit, Michigan and DuPage County, Illinois perceived local COVID-19 transmission when surveyed to be low or moderate, despite documented sustained high transmission. Higher perceived local COVID-19 transmission was associated with more use of preventive behaviors, overall and in response to high local COVID-19 transmission.
Four percent of children aged 6 months–4 years had received ≥1 doses of COVID-19 vaccine based on interviews conducted during July 2022; 59% were unvaccinated, but the parent was open to vaccinating their child; and 37% were unvaccinated and the parent was reluctant to vaccinate. Among parents open to vaccination, 25% reported receiving a provider recommendation, and 57% were confident of the vaccine’s safety; confidence of vaccine safety varied by race or ethnicity and household income.
Introduction In addition to the original monovalent vaccines available for SARS-CoV-2, bivalent vaccines covering wild-type (WT) and Omicron BA.1 are also available. However, there is a lack of real-world data on the effectiveness of bivalent vaccines as second boosters on the dominant Omicron sublineages, including BA.2 and BA.5. Methods This prospective longitudinal cohort study was conducted at Toyama University Hospital, a tertiary medical center in Japan. Participants (n = 565) who received the first booster vaccination were followed up until 2 weeks after the second booster dose of the monovalent mRNA-1273 (WT group, n = 168) and bivalent BNT162b2 (WT+BA.1 group, n = 23) vaccines. Participants with previous SARS-CoV-2 infections were excluded from the study. Anti-receptor-binding domain (RBD) antibody levels and neutralizing activity were measured. Vaccine-related symptoms were also assessed using a questionnaire after the second booster dose. Results The anti-RBD antibody levels after the second booster dose in the WT and WT+BA.1 group were similar (median [inter quartile], 26262.0 [16951.0-38137.0] U/mL vs. 24840.0 [14828.0-41460.0] U/mL, respectively). Although the neutralization activity of the pooled sera of the WT+BA.1 group was the lowest against BA.5, the activities against BA.2 and BA.5 were higher than those of the WT group in both pseudotyped and live virus assays. Vaccine-related symptoms, including systemic and local symptoms, were strongly correlated with anti-RBD antibody levels and neutralizing titers with significant differences. Conclusion The second booster dose of the bivalent (WT/Omicron BA.1) vaccine induced higher neutralizing activity against BA.2 and BA.5 than that of the original.
In this cross-sectional study of NFL games attended by a total 1.3 million fans, the presence of large numbers of fans at NFL games was associated with increases in the incidence of COVID-19 cases both in the counties in which these venues were located and contiguous counties. Specifically, NFL games that had 20 000 fans in attendance had 2.23 times the rate of spikes in COVID-19, but NFL games with fewer than 5000 fans in attendance did not generate any spikes.
In 5-11-year-old children mRNA-vaccines are moderately effective against infections with the Omicron variant, but probably still protect well against COVID-19 hospitalisations. Vaccines were reactogenic but generally safe.
November 17, 2022
The BNT162b2 bivalent BA.4/5 COVID-19 vaccine has been authorized to mitigate COVID-19 due to current Omicron and potentially future variants. New sublineages of SARS-CoV-2 Omicron continue to emerge and have acquired additional mutations, particularly in the spike protein, that may lead to improved viral fitness and immune evasion. The present study characterized neutralization activities against new Omicron sublineages BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 after a 4th dose (following three doses of BNT162b2) of either the original monovalent BNT162b2 or the bivalent BA.4/5 booster in individuals >55 years of age. For all participants, the 4th dose of monovalent BNT162b2 vaccine induced a 3.0, 2.9, 2.3, 2.1, 1.8, and 1.5 geometric mean neutralizing titer fold rise (GMFR) against USA/WA1-2020 (a strain isolated in January 2020), BA.4/5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1, respectively; the bivalent vaccine induced 5.8, 13.0, 11.1, 6.7, 8.7, and 4.8 GMFRs. For individuals without SARS-CoV-2 infection history, BNT162b2 monovalent induced 4.4, 3.0, 2.5, 2.0, 1.5, and 1.3 GMFRs, respectively; the bivalent vaccine induced 9.9, 26.4, 22.2, 8.4, 12.6, and 4.7 GMFRs. These data suggest the bivalent BA.4/5 vaccine is more immunogenic than the original BNT162b2 monovalent vaccine against circulating Omicron sublineages, including BQ.1.1 that is becoming prevalent globally.
Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies
Convergent evolution of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 lineages has led to the emergence of several new subvariants, including BA.2.75.2, BA.4.6. and BQ.1.1. The subvariants BA.2.75.2 and BQ.1.1 are expected to become predominant in many countries in November 2022. They carry an additional and often redundant set of mutations in the spike, likely responsible for increased transmissibility and immune evasion. Here, we established a viral amplification procedure to easily isolate Omicron strains. We examined their sensitivity to 6 therapeutic monoclonal antibodies (mAbs) and to 72 sera from Pfizer BNT162b2-vaccinated individuals, with or without BA.1/BA.2 or BA.5 breakthrough infection. Ronapreve (Casirivimab and Imdevimab) and Evusheld (Cilgavimab and Tixagevimab) lost any antiviral efficacy against BA.2.75.2 and BQ.1.1, whereas Xevudy (Sotrovimab) remained weakly active. BQ.1.1 was also resistant to Bebtelovimab. Neutralizing titers in triply vaccinated individuals were low to undetectable against BQ.1.1 and BA.2.75.2, 4 months after boosting. A BA.1/BA.2 breakthrough infection increased these titers, which remained about 18-fold lower against BA.2.75.2 and BQ.1.1, than against BA.1. Reciprocally, a BA.5 breakthrough infection increased more efficiently neutralization against BA.5 and BQ.1.1 than against BA.2.75.2. Thus, the evolution trajectory of novel Omicron subvariants facilitated their spread in immunized populations and raises concerns about the efficacy of most currently available mAbs.
Background and objective Ecological studies indicate ambient particulate matter ≤2.5mm (PM2.5) air pollution is associated with poorer COVID-19 outcomes. However, these studies cannot account for individual heterogeneity and often have imprecise estimates of PM2.5 exposure. We review evidence from studies using individual-level data to determine whether PM2.5 increases risk of COVID-19 infection, severe disease, and death. Methods Systematic review of case-control and cohort studies, searching Medline, Embase, and WHO COVID-19 up to 30 June 2022. Study quality was evaluated using the Newcastle-Ottawa Scale. Results were pooled with a random effects meta-analysis, with Egger′s regression, funnel plots, and leave-one-out and trim-and-fill analyses to adjust for publication bias. Results N=18 studies met inclusion criteria. A 10μg/m3 increase in PM2.5 exposure was associated with 66% (95% CI: 1.31-2.11) greater odds of COVID-19 infection (N=7) and 127% (95% CI: 1.41-3.66) increase in severe illness (hospitalisation or worse) (N=6). Pooled mortality results (N=5) were positive but non-significant (OR 1.40; 0.94 to 2.10). Most studies were rated "good" quality (14/18 studies), though there were numerous methodological issues; few used individual-level data to adjust for confounders like socioeconomic status (4/18 studies), instead using area-based indicators (12/18 studies) or not adjusting for it (3/18 studies). Most severity (9/10 studies) and mortality studies (5/6 studies) were based on people already diagnosed COVID-19, potentially introducing collider bias. Conclusion There is strong evidence that ambient PM2.5 increases the risk of COVID-19 infection, and weaker evidence of increases in severe disease and mortality.
November 16, 2022
Associations between indoor relative humidity and global COVID-19 outcomes
Globally, the spread and severity of COVID-19 have been distinctly non-uniform. Seasonality was suggested as a contributor to regional variability, but the relationship between weather and COVID-19 remains unclear and the focus of attention has been on outdoor conditions. Because humans spend most of their time indoors and because most transmission occurs indoors, we here, instead, investigate the hypothesis that indoor climate—particularly indoor relative humidity (RH)—may be the more relevant modulator of outbreaks. To study this association, we combined population-based COVID-19 statistics and meteorological measurements from 121 countries. We rigorously processed epidemiological data to reduce bias, then developed and experimentally validated a computational workflow to estimate indoor conditions based on outdoor weather data and standard indoor comfort conditions. Our comprehensive analysis shows robust and systematic relationships between regional outbreaks and indoor RH. In particular, we found intermediate RH (40–60%) to be robustly associated with better COVID-19 outbreak outcomes (versus RH < 40% or >60%). Together, these results suggest that indoor conditions, particularly indoor RH, modulate the spread and severity of COVID-19 outbreaks.
November 15, 2022
Risk for newly diagnosed diabetes after COVID-19: a systematic review and meta-analysis
After COVID-19, patients of all ages and genders had an elevated incidence and relative risk for a new diagnosis of diabetes. Particular attention should be paid during the first 3 months of follow-up after COVID-19 for new-onset diabetes.
Introduction: The uptake of Paxlovid in individuals infected with COVID-19 has been significantly limited by concerns around the Paxlovid rebound phenomenon despite the scarcity of evidence around its epidemiology. The purpose of this study was to prospectively compare the epidemiology of Paxlovid rebound in treated and untreated participants with acute COVID-19 infection Methods: We designed a digital, prospective observational study, which included participants who tested positive for COVID-19 and were clinically eligible for Paxlovid. Participants were assigned to a Paxlovid or control group based on their decision to take the medication. Both groups were provided 12 rapid antigen tests and asked to test and answer symptom surveys on a regular frequent schedule for 16 days. Viral rebound based on test results and COVID-19 symptom rebound based on patient reported symptoms were evaluated. Results: Viral rebound incidence was 14.2% in the Paxlovid group (n=127) and 9.3% in the control group (n=43). COVID-19 symptom rebound incidence was higher in the Paxlovid group (18.9%) compared to the control group (7.0%). There were no notable differences in viral rebound by age, gender, pre-existing conditions, or major symptom groups during the acute phase or at the 1-month interval. Conclusion: This preliminary report of our prospective study suggests that rebound after clearance of test positivity or symptom resolution is higher than previously reported. However, we observed a similar rate of rebound in both in the Paxlovid and control groups. Large studies with diverse participants and extended follow-up are needed to better understand the rebound phenomena.
In this study, contradictions to nirmatrelvir-ritonavir were prevalent in individuals hospitalized with COVID-19, as previously suggested. These findings also alert researchers to the risk of confounding by contraindication in observational studies focused on nirmatrelvir-ritonavir, which may overestimate treatment efficacy if not excluding patients with contraindications to this treatment. In addition, some of the contraindicated medications listed here could be temporarily held in the context of using nirmatrelvir-ritonavir.
November 11, 2022
Although population-based COVID-19–associated hospitalization rates among infants aged <6 months increased in the Omicron variant–predominant periods compared with the Delta variant–predominant period, indicators of the most severe disease among hospitalized infants aged <6 months did not.
Bivalent COVID-19 vaccine booster doses might improve protection against SARS-CoV-2 Omicron sublineages and, along with completion of a primary series in persons who remain unvaccinated, are important to protect against COVID-19, particularly among those persons who are at increased risk for severe illness and death.
November 10, 2022
The landscape of mRNA nanomedicine
Messenger RNA (mRNA) is an emerging class of therapeutic agent for the prevention and treatment of a wide range of diseases. The recent success of the two highly efficacious mRNA vaccines produced by Moderna and Pfizer–BioNTech to protect against COVID-19 highlights the huge potential of mRNA technology for revolutionizing life science and medical research. Challenges related to mRNA stability and immunogenicity, as well as in vivo delivery and the ability to cross multiple biological barriers, have been largely addressed by recent progress in mRNA engineering and delivery. In this Review, we present the latest advances and innovations in the growing field of mRNA nanomedicine, in the context of ongoing clinical translation and future directions to improve clinical efficacy.
Numerous safe and effective COVID-19 vaccines have been developed worldwide that utilize various delivery technologies and engineering strategies. We show here that vaccines containing prefusion-stabilizing S mutations elicit antibody responses in humans with enhanced recognition of S and the S1 subunit relative to postfusion S, as compared to vaccines lacking these mutations or natural infection. Prefusion S and S1 antibody binding titers positively and equivalently correlated with neutralizing activity and depletion of S1-directed antibodies completely abrogated plasma neutralizing activity. We show that neutralizing activity is almost entirely directed to the S1 subunit and that variant cross-neutralization is mediated solely by RBD-specific antibodies. Our data provide a quantitative framework for guiding future S engineering efforts to develop vaccines with higher resilience to the emergence of variants than current technologies.
Long-term health sequelae of the Coronavirus Disease 2019 (COVID-19) are a major public health concern. However, evidence on post-acute COVID-19 syndrome (post-COVID-19) is still limited, particularly for children and adolescents. Utilizing comprehensive healthcare data on approximately 46% of the German population, we investigated post-COVID-19-associated morbidity in children/adolescents and adults.
Divergent SARS-CoV-2 variant emerges in white-tailed deer with deer-to-human transmission
Wildlife reservoirs of broad-host-range viruses have the potential to enable evolution of viral variants that can emerge to infect humans. In North America, there is phylogenomic evidence of continual transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans to white-tailed deer (Odocoileus virginianus) through unknown means, but no evidence of transmission from deer to humans. We carried out an observational surveillance study in Ontario, Canada during November and December 2021 (n = 300 deer) and identified a highly divergent lineage of SARS-CoV-2 in white-tailed deer (B.1.641). This lineage is one of the most divergent SARS-CoV-2 lineages identified so far, with 76 mutations (including 37 previously associated with non-human mammalian hosts). From a set of five complete and two partial deer-derived viral genomes we applied phylogenomic, recombination, selection and mutation spectrum analyses, which provided evidence for evolution and transmission in deer and a shared ancestry with mink-derived virus. Our analysis also revealed an epidemiologically linked human infection. Taken together, our findings provide evidence for sustained evolution of SARS-CoV-2 in white-tailed deer and of deer-to-human transmission.
Acute and postacute sequelae associated with SARS-CoV-2 reinfection
First infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risk of acute and postacute death and sequelae in various organ systems. Whether reinfection adds to risks incurred after first infection is unclear. Here we used the US Department of Veterans Affairs’ national healthcare database to build a cohort of individuals with one SARS-CoV-2 infection (n = 443,588), reinfection (two or more infections, n = 40,947) and a noninfected control (n = 5,334,729). We used inverse probability-weighted survival models to estimate risks and 6-month burdens of death, hospitalization and incident sequelae. Compared to no reinfection, reinfection contributed additional risks of death (hazard ratio (HR) = 2.17, 95% confidence intervals (CI) 1.93–2.45), hospitalization (HR = 3.32, 95% CI 3.13–3.51) and sequelae including pulmonary, cardiovascular, hematological, diabetes, gastrointestinal, kidney, mental health, musculoskeletal and neurological disorders. The risks were evident regardless of vaccination status. The risks were most pronounced in the acute phase but persisted in the postacute phase at 6 months. Compared to noninfected controls, cumulative risks and burdens of repeat infection increased according to the number of infections. Limitations included a cohort of mostly white males. The evidence shows that reinfection further increases risks of death, hospitalization and sequelae in multiple organ systems in the acute and postacute phase. Reducing overall burden of death and disease due to SARS-CoV-2 will require strategies for reinfection prevention.
Cognitive Deficits in Long Covid-19
Some patients who have recovered from an infection have reported transient or even lasting cognitive dysfunction. This includes patients who have been infected with SARS-CoV-2, many of whom, including those with mild disease, have reported deficits in attention, executive functioning, language, processing speed, and memory — symptoms collectively referred to as “brain fog.” Together with increased incidence of anxiety, depression, sleep disorder, and fatigue, this syndrome of cognitive impairment contributes substantially to the morbidity of post–Covid-19 conditions (also called “long Covid”).
November 9, 2022
Six-Month Follow-up after a Fourth BNT162b2 Vaccine Dose
In this prospective cohort study, a third dose of the BNT162b2 vaccine led to an improved and sustained immunologic response as compared with two doses, but the additional immunologic advantage of the fourth dose was much smaller and had waned completely by 13 weeks after vaccination. This finding correlated with waning vaccine effectiveness among recipients of a fourth dose, which culminated in no substantial additional effectiveness over a third dose at 15 to 26 weeks after vaccination. These results suggest that the fourth dose, and possibly future boosters, should be timed wisely to coincide with disease waves or to be available seasonally, similar to the influenza vaccine. Whether multivalent booster doses will result in longer durability remains to be seen.
Lifting Universal Masking in Schools — Covid-19 Incidence among Students and Staff
Among school districts in the greater Boston area, the lifting of masking requirements was associated with an additional 44.9 Covid-19 cases per 1000 students and staff during the 15 weeks after the statewide masking policy was rescinded.
In this cohort study of 585 maternal-newborn dyads, maternal and cord blood IgG antibody levels were higher after vaccination compared with after infection. An association was observed between time from infection or vaccination to delivery and transfer ratio.
November 8, 2022
Innate immune mechanisms of mRNA vaccines
The lipid nanoparticle (LNP)-encapsulated, nucleoside-modified mRNA platform has been used to generate safe and effective vaccines in record time against COVID-19. Here, we review the current understanding of the manner whereby mRNA vaccines induce innate immune activation and how this contributes to protective immunity. We discuss innate immune sensing of mRNA vaccines at the cellular and intracellular levels and consider the contribution of both the mRNA and the LNP components to their immunogenicity. A key message that is emerging from recent observations is that the LNP carrier acts as a powerful adjuvant for this novel vaccine platform. In this context, we highlight important gaps in understanding and discuss how new insight into the mechanisms underlying the effectiveness of mRNA-LNP vaccines may enable tailoring mRNA and carrier molecules to develop vaccines with greater effectiveness and milder adverse events in the future.
November 1, 2022
mRNA bivalent booster enhances neutralization against BA.2.75.2 and BQ.1.1
The emergence of the highly divergent SARS-CoV-2 Omicron variant has jeopardized the efficacy of vaccines based on the ancestral spike. The bivalent COVID-19 mRNA booster vaccine within the United States is comprised of the ancestral and the Omicron BA.5 spike. Since its approval and distribution, additional Omicron subvariants have been identified with key mutations within the spike protein receptor binding domain that are predicted to escape vaccine sera. Of particular concern is the R346T mutation which has arisen in multiple subvariants, including BA.2.75.2 and BQ.1.1. Using a live virus neutralization assay, we evaluated serum samples from individuals who had received either one or two monovalent boosters or the bivalent booster to determine neutralizing activity against wild-type (WA1/2020) virus and Omicron subvariants BA.1, BA.5, BA.2.75.2, and BQ.1.1. In the one monovalent booster cohort, relative to WA1/2020, we observed a reduction in neutralization titers of 9-15-fold against BA.1 and BA.5 and 28-39-fold against BA.2.75.2 and BQ.1.1. In the BA.5-containing bivalent booster cohort, the neutralizing activity improved against all the Omicron subvariants. Relative to WA1/2020, we observed a reduction in neutralization titers of 3.7- and 4-fold against BA.1 and BA.5, respectively, and 11.5- and 21-fold against BA.2.75.2 and BQ.1.1, respectively. These data suggest that the bivalent mRNA booster vaccine broadens humoral immunity against the Omicron subvariants.
COVID-19 primary series and booster vaccination and immune imprinting
Background: Epidemiological evidence for immune imprinting was investigated in immune histories related to vaccination in Qatar from onset of the omicron wave, on December 19, 2021, through September 15, 2022. Methods: Matched, retrospective, cohort studies were conducted to investigate differences in incidence of SARS-CoV-2 reinfection in the national cohort of persons who had a primary omicron infection, but different vaccination histories. History of primary-series (two-dose) vaccination was compared to that of no vaccination, history of booster (three-dose) vaccination was compared to that of two-dose vaccination, and history of booster vaccination was compared to that of no vaccination. Associations were estimated using Cox proportional-hazards regression models. Results: The adjusted hazard ratio comparing incidence of reinfection in the two-dose cohort to that in the unvaccinated cohort was 0.43 (95% CI: 0.38-0.48). The adjusted hazard ratio comparing incidence of reinfection in the three-dose cohort to that in the two-dose cohort was 1.38 (95% CI: 1.16-1.65). The adjusted hazard ratio comparing incidence of reinfection in the three-dose cohort to that in the unvaccinated cohort was 0.53 (95% CI: 0.44-0.63). All adjusted hazard ratios appeared stable over 6 months of follow-up. Divergence in cumulative incidence curves in all comparisons increased markedly when incidence was dominated by BA.4/BA.5 and BA.2.75*. No reinfection in any cohort progressed to severe, critical, or fatal COVID-19. Conclusions: History of primary-series vaccination enhanced immune protection against omicron reinfection, but history of booster vaccination compromised protection against omicron reinfection. These findings do not undermine the short-term public health utility of booster vaccination.
Durable spike-specific T-cell responses after different COVID-19 vaccination regimens are not further enhanced by booster vaccination
Although microbial populations in the gut microbiome are associated with COVID-19 severity, a causal impact on patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. We first demonstrate SARS-CoV-2 infection induces gut microbiome dysbiosis in mice, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Samples collected from 96 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, including blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19.
October 31, 2022
Tracing the origin of SARS-CoV-2 Omicron-like Spike sequences detected in wastewater
Importance: The origin of highly divergent "cryptic" SARS-CoV-2 Spike sequences, which appear in wastewater but not clinical samples, is unknown. These wastewater sequences have harbored many of the same variants that later emerged in Omicron. If these enigmatic sequences are human-derived and transmissible, they could both be a source of future variants and a valuable tool for forecasting sequences that should be incorporated into vaccines and therapeutics. Objective: To determine whether enigmatic SARS-CoV-2 lineages detected in wastewater have a human or non-human (i.e., animal) source. Design: On January 11, 2022, an unusual Spike sequence was detected in municipal wastewater from a metropolitan area. Over the next four months, more focused wastewater sampling resolved the source of this variant. Setting: This study was performed in Wisconsin, United States, which has a comprehensive program for detecting SARS-CoV-2 in wastewater. Participants: Composite wastewater samples were used for this study; therefore, no individuals participated. Main Outcome(s) and Measure(s): The primary outcome was to determine the host(s) responsible for shedding this variant in wastewater. Both human and non-human hosts were plausible candidates at the study's outset. Results: The presence of the cryptic virus was narrowed from a municipal wastewater sample (catchment area >100,000 people) to an indoor wastewater sample from a single facility (catchment area ~30 people), indicating the human origin of this virus. Extraordinarily high concentrations of viral RNA (~520,000,000 genome copies / L and ~1,600,000,000 genome copies / L in June and August 2022, respectively) were detected in the indoor wastewater sample. The virus sequence harbored a combination of fixed nucleotide substitutions previously observed only in Pango lineage B.1.234, a variant that circulated at low levels in Wisconsin from October 2020 to February 2021. Conclusions and Relevance: High levels of persistent SARS-CoV-2 shedding from the gastrointestinal tract of an infected individual likely explain the presence of evolutionarily advanced, "cryptic variants" observed in some wastewater samples.
October 30, 2022
Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution
Continuous evolution of Omicron has led to a rapid and simultaneous emergence of numerous variants that display growth advantages over BA. 5. Despite their divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots. The driving force and destination of such convergent evolution and its impact on humoral immunity remain unclear. Here, we demonstrate that these convergent mutations can cause striking evasion of neutralizing antibody (NAb) drugs and convalescent plasma, including those from BA.5 breakthrough infection, while maintaining sufficient ACE2 binding capability. BQ.1.1.10, BA.4.6.3, XBB, and CH. 1.1 are the most antibody-evasive strain tested, even exceeding SARS-CoV-1 level. To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies (mAbs) isolated from BA.2 and BA.5 breakthrough-infection convalescents. Importantly, due to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection caused significant reductions in the epitope diversity of NAbs and increased proportion of non-neutralizing mAbs, which in turn concentrated humoral immune pressure and promoted convergent evolution. Moreover, we showed that the convergent RBD mutations could be accurately inferred by integrated deep mutational scanning (DMS) profiles, and the evolution trends of BA.2.75/BA.5 subvariants could be well-simulated through constructed convergent pseudovirus mutants. Together, our results suggest current herd immunity and BA.5 vaccine boosters may not provide good protection against infection. Broad-spectrum SARS-CoV-2 vaccines and NAb drugs development should be highly prioritized, and the constructed mutants could help to examine their effectiveness in advance.
October 26, 2022
A primary focus of research on conspiracy theories has been understanding the psychological characteristics that predict people’s level of conspiracist ideation. However, the dynamics of conspiracist ideation—i.e., how such tendencies change over time—are not well understood. To help fill this gap in the literature, we used data from two longitudinal studies (Study 1 N = 107; Study 2 N = 1,037) conducted during the COVID-19 pandemic. We find that greater belief in COVID-19 conspiracy theories at baseline predicts both greater endorsement of a novel real-world conspiracy theory involving voter fraud in the 2020 American Presidential election (Study 1) and increases in generic conspiracist ideation over a period of several months (Studies 1 and 2). Thus, engaging with real-world conspiracy theories appears to act as a gateway, leading to more general increases in conspiracist ideation. Beyond enhancing our knowledge of conspiracist ideation, this work highlights the importance of fighting the spread of conspiracy theories.
Protection against Omicron from Vaccination and Previous Infection in a Prison System
Our findings in two high-risk populations suggest that mRNA vaccination and previous infection were effective against omicron infection, with lower estimates among those infected before the period of delta predominance. Three vaccine doses offered significantly more protection than two doses, including among previously infected persons.
October 25, 2022
BNT162b2 vaccine effectiveness against SARS-CoV-2 omicron BA.4 and BA.5
Our results suggest that two doses of BNT162b2 offered little protection against all BA.4/5 outcomes measured, including hospital admission. A booster (third or fourth dose) did provide protection against BA.4/5, but this protection probably wanes after 3 months against milder outcomes like outpatient, urgent care, or emergency department encounters and after roughly 6 months against BA.4/5-related hospitalisation.
Immunogenicity of the BA.5 Bivalent mRNA Vaccine Boosters
Waning immunity following mRNA vaccination and the emergence of SARS-CoV-2 variants has led to reduced mRNA vaccine efficacy against both symptomatic infection and severe disease. Bivalent mRNA boosters expressing the Omicron BA.5 and ancestral WA1/2020 Spike proteins have been developed and approved, because BA.5 is currently the dominant SARS-CoV-2 variant and substantially evades neutralizing antibodies (NAbs). Our data show that BA.5 NAb titers were comparable following monovalent and bivalent mRNA boosters.
Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication
Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or who experience breakthrough infections. Understanding the common host factors necessary for the life cycles of coronaviruses may reveal conserved therapeutic targets. Here, we used the known substrate specificities of mammalian protein kinases to deconvolute the sequence of phosphorylation events mediated by three host protein kinase families (SRPK, GSK-3, and CK1) that coordinately phosphorylate a cluster of serine and threonine residues in the viral N protein, which is required for viral replication. We also showed that loss or inhibition of SRPK1/2, which we propose initiates the N protein phosphorylation cascade, compromised the viral replication cycle. Because these phosphorylation sites are highly conserved across coronaviruses, inhibitors of these protein kinases not only may have therapeutic potential against COVID-19 but also may be broadly useful against coronavirus-mediated diseases.
October 24, 2022
Regular physical activity was associated with improved vaccine effectiveness against COVID-19 hospitalisation, with higher levels of physical activity associated with greater vaccine effectiveness. Physical activity enhances vaccine effectiveness against severe COVID-19 outcomes and should be encouraged by greater public health messaging.
Antibody responses to Omicron BA.4/BA.5 bivalent mRNA vaccine booster shot
The SARS-CoV-2 Omicron variant and its numerous sub-lineages have exhibited a striking ability to evade humoral immune responses induced by prior vaccination or infection. The Food and Drug Administration (FDA) has recently granted Emergency Use Authorizations (EUAs) to new bivalent formulations of the original Moderna and Pfizer mRNA SARS-CoV-2 vaccines that target both the ancestral strain as well as the Omicron BA.4/BA.5 variant. Despite their widespread use as a vaccine boost, little is known about the antibody responses induced in humans. Here, we collected sera from several clinical cohorts: individuals after three or four doses of the original monovalent mRNA vaccines, individuals receiving the new bivalent vaccines as a fourth dose, and individuals with BA.4/BA.5 breakthrough infection following mRNA vaccination. Using pseudovirus neutralization assays, these sera were tested for neutralization against an ancestral SARS-CoV-2 strain, several Omicron sub-lineages, and several related sarbecoviruses. At ~3-5 weeks post booster shot, individuals who received a fourth vaccine dose with a bivalent mRNA vaccine targeting BA.4/BA.5 had similar neutralizing antibody titers as those receiving a fourth monovalent mRNA vaccine against all SARS-CoV-2 variants tested, including BA.4/BA.5. Those who received a fourth monovalent vaccine dose had a slightly higher neutralizing antibody titers than those who received the bivalent vaccine against three related sarbecoviruses: SARS-CoV, GD-Pangolin, and WIV1. When given as a fourth dose, a bivalent mRNA vaccine targeting Omicron BA.4/BA.5 and an ancestral SARS-CoV-2 strain did not induce superior neutralizing antibody responses in humans, at the time period tested, compared to the original monovalent vaccine formulation.
October 23, 2022
A booster is your best shot now
For now, the best defense we have against the BQ.1.1-led wave is to get a booster. It will markedly raise neutralizing antibodies and our cellular immune response, and just-in-time to broaden our immunity to be ready for BQ.1.1 and related variants with marked immune evasiveness. As you well know, it takes a couple of weeks to get the immune response built, so this is the right time to get it done. It will help prevent severe Covid for at least 4-5 months ahead. Be ready. The pandemic isn’t over—yet. Preserve your health and that of your family, friends, and network.
Sterilizing immunity: Understanding COVID-19
Immune memory develops during primary infections to protect from future exposures to the same pathogen. Vaccines mimic this response and induce immune memory that protects from severe disease, and in some cases, from symptomatic infection. If the pathogen is eliminated before it can replicate, natural and vaccine-induced immune memory can prevent the establishment of the infection, mediating sterilizing immunity. Sterilizing immunity protects the individual and prevents transmission to new hosts thereby contributing to protection at a population level. Here, we describe the basic concepts of sterilizing immunity and discuss its relevance for protection in the context of SARS-CoV-2.
October 22, 2022
Previous infection with pre-Omicron variants was the strongest risk factor for reporting PASC symptoms in this HCW cohort. A definite influence of prior vaccination on the prevention of PASC after Omicron BA.1 infection was not measurable.
October 17, 2022
Therapeutic advances in COVID-19
Over 2 years have passed since the start of the COVID-19 pandemic, which has claimed millions of lives. Unlike the early days of the pandemic, when management decisions were based on extrapolations from in vitro data, case reports and case series, clinicians are now equipped with an armamentarium of therapies based on high-quality evidence. These treatments are spread across seven main therapeutic categories: anti-inflammatory agents, antivirals, antithrombotics, therapies for acute hypoxaemic respiratory failure, anti-SARS-CoV-2 (neutralizing) antibody therapies, modulators of the renin–angiotensin–aldosterone system and vitamins. For each of these treatments, the patient population characteristics and clinical settings in which they were studied are important considerations. Although few direct comparisons have been performed, the evidence base and magnitude of benefit for anti-inflammatory and antiviral agents clearly outweigh those of other therapeutic approaches such as vitamins. The emergence of novel variants has further complicated the interpretation of much of the available evidence, particularly for antibody therapies. Importantly, patients with acute and chronic kidney disease were under-represented in many of the COVID-19 clinical trials, and outcomes in this population might differ from those reported in the general population. Here, we examine the clinical evidence for these therapies through a kidney medicine lens.
Salivary glands act as virus reservoirs in various infectious diseases and have been reported to be targeted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the mechanisms underlying infection and replication in salivary glands are still enigmatic due to the lack of proper in vitro models. Here, we show that human induced salivary glands (hiSGs) generated from human induced pluripotent stem cells can be infected with SARS-CoV-2. The hiSGs exhibit properties similar to those of embryonic salivary glands and are a valuable tool for the functional analysis of genes during development. Orthotopically transplanted hiSGs can be engrafted at a recipient site in mice and show a mature phenotype. In addition, we confirm SARS-CoV-2 infection and replication in hiSGs. SARS-CoV-2 derived from saliva in asymptomatic individuals may participate in the spread of the virus. hiSGs may be a promising model for investigating the role of salivary glands as a virus reservoir.
Life expectancy changes since COVID-19
The COVID-19 pandemic triggered an unprecedented rise in mortality that translated into life expectancy losses around the world, with only a few exceptions. We estimate life expectancy changes in 29 countries since 2020 (including most of Europe, the United States and Chile), attribute them to mortality changes by age group and compare them with historic life expectancy shocks. Our results show divergence in mortality impacts of the pandemic in 2021. While countries in western Europe experienced bounce backs from life expectancy losses of 2020, eastern Europe and the United States witnessed sustained and substantial life expectancy deficits. Life expectancy deficits during fall/winter 2021 among people ages 60+ and <60 were negatively correlated with measures of vaccination uptake across countries (r60+ = −0.86; two-tailed P < 0.001; 95% confidence interval, −0.94 to −0.69; r<60 = −0.74; two-tailed P < 0.001; 95% confidence interval, −0.88 to −0.46). In contrast to 2020, the age profile of excess mortality in 2021 was younger, with those in under-80 age groups contributing more to life expectancy losses. However, even in 2021, registered COVID-19 deaths continued to account for most life expectancy losses.
October 14, 2022
The prevalences of poor current mental health and past-year suicide attempts among adolescents reporting four or more ACEs during the COVID-19 pandemic were four and 25 times as high as those without ACEs, respectively. Exposure to specific ACE types (e.g., emotional abuse) were associated with higher prevalences of poor mental health and suicidal behaviors.
October 12, 2022
Outcomes among confirmed cases and a matched comparison group in the Long-COVID in Scotland study
With increasing numbers infected by SARS-CoV-2, understanding long-COVID is essential to inform health and social care support. A Scottish population cohort of 33,281 laboratory-confirmed SARS-CoV-2 infections and 62,957 never-infected individuals were followed-up via 6, 12 and 18-month questionnaires and linkage to hospitalization and death records. Of the 31,486 symptomatic infections,1,856 (6%) had not recovered and 13,350 (42%) only partially. No recovery was associated with hospitalized infection, age, female sex, deprivation, respiratory disease, depression and multimorbidity. Previous symptomatic infection was associated with poorer quality of life, impairment across all daily activities and 24 persistent symptoms including breathlessness (OR 3.43, 95% CI 3.29–3.58), palpitations (OR 2.51, OR 2.36–2.66), chest pain (OR 2.09, 95% CI 1.96–2.23), and confusion (OR 2.92, 95% CI 2.78–3.07). Asymptomatic infection was not associated with adverse outcomes. Vaccination was associated with reduced risk of seven symptoms. Here we describe the nature of long-COVID and the factors associated with it.
October 11, 2022
Booster mRNA vaccination was highly effective in preventing death and moderately effective in preventing infection and hospitalization for up to 4 months after administration in the Omicron era. Increased uptake of booster vaccination, which is currently suboptimal, should be pursued to limit the morbidity and mortality of SARS-CoV-2 infection, especially in persons with high comorbidity burden.
COVID jabs for kids: they’re safe and they work — so why is uptake so patchy?
Some countries are now offering COVID vaccines for children as young as six months. Nature looks at how effective they are and why more kids haven’t had them.
October 10, 2022
DCT with 24 h exemption from self-isolation for essential activities appears to be non-inferior to self-isolation. This study, which provided evidence for the UK Government's daily lateral flow testing policy for vaccinated contacts of COVID-19 cases, indicated that daily testing with LFDs could allow individuals to reduce the risk of onward transmission while minimising the adverse effects of self-isolation. Although contacts in England are no longer required to isolate, the findings will be relevant for future policy decisions around COVID-19 or other communicable infections.
In this cross-sectional study of 63 277 participants conducted at a walk-up community testing site, patients more commonly reported COVID-19 upper respiratory tract symptoms during the Omicron BA.1 period than the pre-Delta and Delta periods, with differences by vaccination status and age. During the Omicron BA.1 period, 5 days after symptom onset, 80% of participants remained positive via a rapid antigen test.
This observational analysis involved bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. The modeled estimated proportion with at least 1 of the 3 self-reported Long COVID symptom clusters 3 months after symptomatic SARS-CoV-2 infection was 6.2%, including 3.7% for ongoing respiratory problems, 3.2% for persistent fatigue with bodily pain or mood swings, and 2.2% for cognitive problems after adjusting for health status before COVID-19.
October 7, 2022
Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can experience life-threatening respiratory distress, blood pressure dysregulation, and thrombosis. This is thought to be associated with an impaired activity of angiotensin-converting enzyme 2 (ACE2), which is the main entry receptor of SARS-CoV-2 and which also tightly regulates blood pressure by converting the vasoconstrictive peptide angiotensin II (AngII) to a vasopressor peptide. Here, we show that a significant proportion of hospitalized patients with COVID-19 developed autoantibodies against AngII, whose presence correlates with lower blood oxygenation, blood pressure dysregulation, and overall higher disease severity. Anti-AngII antibodies can develop upon specific immune reaction to the SARS-CoV-2 proteins Spike or receptor-binding domain (RBD), to which they can cross-bind, suggesting some epitope mimicry between AngII and Spike/RBD. These results provide important insights on how an immune reaction against SARS-CoV-2 can impair blood pressure regulation.
October 6, 2022
The Neurobiology of Long COVID
Persistent neurological and neuropsychiatric symptoms affect a substantial fraction of people after COVID-19 and represent a major component of the post-acute COVID syndrome, also known as long COVID. Here, we review what is understood about the pathobiology of post-acute COVID-19 impacts on the CNS and discuss possible neurobiological underpinnings of the cognitive symptoms affecting COVID-19 survivors. We propose the chief mechanisms that may contribute to this emerging neurological health crisis.
October 5, 2022
SARS-CoV-2 disrupts host epigenetic regulation via histone mimicry
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and caused the devastating global pandemic of coronavirus disease 2019 (COVID-19), in part because of its ability to effectively suppress host cell responses. In rare cases, viral proteins dampen antiviral responses by mimicking critical regions of human histone proteins, particularly those containing post-translational modifications required for transcriptional regulation. Recent work has demonstrated that SARS-CoV-2 markedly disrupts host cell epigenetic regulation. However, how SARS-CoV-2 controls the host cell epigenome and whether it uses histone mimicry to do so remain unclear. Here we show that the SARS-CoV-2 protein encoded by ORF8 (ORF8) functions as a histone mimic of the ARKS motifs in histone H3 to disrupt host cell epigenetic regulation. ORF8 is associated with chromatin, disrupts regulation of critical histone post-translational modifications and promotes chromatin compaction. Deletion of either the ORF8 gene or the histone mimic site attenuates the ability of SARS-CoV-2 to disrupt host cell chromatin, affects the transcriptional response to infection and attenuates viral genome copy number. These findings demonstrate a new function of ORF8 and a mechanism through which SARS-CoV-2 disrupts host cell epigenetic regulation. Further, this work provides a molecular basis for the finding that SARS-CoV-2 lacking ORF8 is associated with decreased severity of COVID-19.
Overall, our results show that serum from COVID-19 patients with delirium can negatively affect hippocampal-dependent neurogenic processes, and that this effect is mediated by IL6-induced production of the downstream inflammatory cytokines IL12 and IL13, which are ultimately responsible for the detrimental cellular outcomes.
October 4, 2022
Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution
Continuous evolution of Omicron has led to numerous subvariants that exhibit growth advantage over BA.5. Such rapid and simultaneous emergence of variants with enormous advantages is unprecedented. Despite their rapidly divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots, including R346, K356, K444, L452, N460K and F486. The driving force and destination of such convergent evolution and its impact on humoral immunity established by vaccination and infection remain unclear. Here, we demonstrate that these convergent mutations can cause striking evasion of convalescent plasma, including those from BA.5 breakthrough infection, and existing antibody drugs, including Evusheld and Bebtelovimab. BR.2, CA.1, BQ.1.1, and especially XBB, are the most antibody-evasive strain tested, far exceeding BA.5 and approaching SARS-CoV-1 level. To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies (mAbs) isolated from BA.2 and BA.5 breakthrough-infection convalescents. Importantly, due to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection caused significant reductions in the epitope diversity of neutralizing antibodies and increased proportion of non-neutralizing mAbs, which in turn concentrated humoral immune pressure and promoted the convergent RBD evolution. Additionally, the precise convergent RBD mutations and evolution trends of BA.2.75/BA.5 subvariants could be inferred by integrating the neutralization-weighted DMS profiles of mAbs from various immune histories (3051 mAbs in total). Moreover, we demonstrated that as few as five additional convergent mutations based on BA.5 or BA.2.75 could completely evade most plasma samples, including those from BA.5 breakthrough infection, while retaining sufficient hACE2-binding affinity. These results suggest that current herd immunity and BA.5 vaccine boosters may not provide sufficiently broad protection against infection. Broad-spectrum SARS-CoV-2 vaccines and NAb drugs development should be of high priority, and the constructed convergent mutants could serve to examine their effectiveness in advance.
Protease inhibitors are among the most powerful antiviral drugs. Nirmatrelvir is the first protease inhibitor against the SARS-CoV-2 protease 3CLpro that has been licensed for clinical use. To identify mutations that confer resistance to this protease inhibitor, we engineered a chimeric vesicular stomatitis virus (VSV) that expressed a polyprotein composed of the VSV glycoprotein G, the SARS-CoV-2 3CLpro, and the VSV polymerase L. Viral replication was thus dependent on the autocatalytic processing of this precursor protein by 3CLpro and release of the functional viral polymerase L, and replication of this chimeric VSV was effectively inhibited by nirmatrelvir. Using this system, we applied nirmatrelvir to select for resistance mutations. Resistance was confirmed by retesting nirmatrelvir against the selected mutations in an additional VSV-based systems, in an independently developed cellular system, in a biochemical assay, and in a recombinant SARS-CoV-2 system. We demonstrate that some mutants are cross-resistant to ensitrelvir and GC376, whereas others are less resistant to these compounds. Furthermore, we found that most of these resistance mutations already existed in SARS-CoV-2 sequences that have been deposited in the NCBI and GISAID databases, indicating that these mutations were present in circulating SARS-CoV-2 strains.
In this population-based surveillance, we found that myocarditis/pericarditis 0 to 7 days after mRNA vaccination in persons aged 5 to 39 years occurred in approximately 1 in 200 000 doses after the first dose and 1 in 30 000 doses after second dose of the primary series, and 1 in 50 000 doses after the first booster. The incidence varied markedly by age and sex, however, with a disproportionate number of cases occurring in male persons, notably among adolescents after dose 2 and first boosters.
October 3, 2022
How COVID-19 shaped mental health: from infection to pandemic effects
The Coronavirus Disease 2019 (COVID-19) pandemic has threatened global mental health, both indirectly via disruptive societal changes and directly via neuropsychiatric sequelae after SARS-CoV-2 infection. Despite a small increase in self-reported mental health problems, this has (so far) not translated into objectively measurable increased rates of mental disorders, self-harm or suicide rates at the population level. This could suggest effective resilience and adaptation, but there is substantial heterogeneity among subgroups, and time-lag effects may also exist. With regard to COVID-19 itself, both acute and post-acute neuropsychiatric sequelae have become apparent, with high prevalence of fatigue, cognitive impairments and anxiety and depressive symptoms, even months after infection. To understand how COVID-19 continues to shape mental health in the longer term, fine-grained, well-controlled longitudinal data at the (neuro)biological, individual and societal levels remain essential. For future pandemics, policymakers and clinicians should prioritize mental health from the outset to identify and protect those at risk and promote long-term resilience.
Long COVID: defining the role of rheumatology in care and research
There are currently many more questions than answers regarding long COVID and the evolving role of rheumatology in treating this patient population. Overall, given the many unknowns surrounding the syndrome, rheumatologists are well positioned to contribute to basic and clinical research, as well as to care pathways for patients with long COVID, including patients with underlying rheumatic diseases and those with rheumatic complaints. At present, rheumatologists and other subspecialists are limited to some of the foremost tools in our armamentarium (ones that we have long offered to legions of patients with incurable chronic diseases): careful listening, providing validation, and offering empathy. These tools, although in themselves not curative, for now could help patients with long COVID.
October 1, 2022
Studies have reported reduced natural SARS-CoV-2 infection- and vaccine-induced neutralization against Omicron BA.4/BA.5 compared with earlier Omicron subvariants. We conducted a test-negative case–control study evaluating mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with Omicron subvariants. The study included 30,809 SARS-CoV-2 positive and 92,427 SARS-CoV-2 negative individuals aged ≥18 years tested during 1/1/2022-6/30/2022. While 3-dose VE against BA.1 infection was high and waned slowly, VE against BA.2, BA.2.12.1, BA.4, and BA.5 infection was initially moderate to high (61.0%-90.6% 14-30 days post third dose) and waned rapidly. The 4-dose VE against infection with BA.2, BA.2.12.1, and BA.4 ranged between 64.3%-75.7%, and was low (30.8%) against BA.5 14-30 days post fourth dose, disappearing beyond 90 days for all subvariants. The 3-dose VE against hospitalization for BA.1, BA.2, and BA.4/BA.5 was 97.5%, 82.0%, and 72.4%, respectively; 4-dose VE against hospitalization for BA.4/BA.5 was 88.5%. Evaluation of the updated bivalent booster is warranted.
September 28, 2022
Plasma proteomic signature predicts who will get persistent symptoms following SARS-CoV-2 infection
Our findings show that non-severe SARS-CoV-2 infection perturbs the plasma proteome for at least 6 weeks. The plasma proteomic signature at the time of seroconversion has the potential to identify which individuals are more likely to suffer from persistent symptoms related to SARS-CoV-2 infection.
September 26, 2022
Impact of cross-coronavirus immunity in post-acute sequelae of COVID-19
Beyond the unpredictable acute illness caused by SARS-CoV-2, one-fifth of infections unpredictably result in long-term persistence of symptoms despite the apparent clearance of infection. Insights into the mechanisms that underlie post-acute sequelae of COVID-19 (PASC) will be critical for the prevention and clinical management of long-term complications of COVID-19. Several hypotheses have been proposed that may account for the development of PASC, including persistence of virus or the dysregulation of immunity. Among the immunological changes noted in PASC, alterations in humoral immunity have been observed in some patient subsets. To begin to determine whether SARS-CoV-2 or other pathogen specific humoral immune responses evolve uniquely in PASC, we performed comprehensive antibody profiling against SARS-CoV-2 and a panel of endemic pathogens or routine vaccine antigens using Systems Serology in a cohort of patients with pre-existing rheumatic disease who either developed or did not develop PASC. A distinct humoral immune response was observed in individuals with PASC. Specifically, individuals with PASC harbored less inflamed and weaker Fcγ receptor binding anti-SARS-CoV-2 antibodies and a significantly expanded and more inflamed antibody response against endemic Coronavirus OC43. Individuals with PASC, further, generated more avid IgM responses and developed an expanded inflammatory OC43 S2-specific Fc-receptor binding response, linked to cross reactivity across SARS-CoV-2 and common coronaviruses. These findings implicate previous common Coronavirus imprinting as a marker for the development of PASC.
In a cohort study of 10.6 million North Carolina residents from March 2020 to June 2022, receipt of a primary COVID-19 vaccine series compared with being unvaccinated, receipt of a booster compared with primary vaccination, and prior SARS-CoV-2 infection compared with no prior infection were all significantly associated with lower risk of SARS-CoV-2 infection and resulting hospitalization and death. The estimates for the associated protection decreased over time, especially for the outcome of infection, and varied by type of circulating variant. Receipt of COVID-19 vaccines and boosters, as well as prior SARS-CoV-2 infection, were associated with protection against SARS-CoV-2 infection (including Omicron) and severe COVID-19 outcomes, although the associated protection waned over time.
September 23, 2022
In this study, new T1D diagnoses were more likely to occur among pediatric patients with prior COVID-19 than among those with other respiratory infections (or with other encounters with health systems). Respiratory infections have previously been associated with onset of T1D,6 but this risk was even higher among those with COVID-19 in our study, raising concern for long-term, post–COVID-19 autoimmune complications among youths. Study limitations include potential biases owing to the observational and retrospective design of the electronic health record analysis, including the possibility of misclassification of diabetes as type 1 vs type 2, and the possibility that additional unidentified factors accounted for the association. Results should be confirmed in other populations. The increased risk of new-onset T1D after COVID-19 adds an important consideration for risk-benefit discussions for prevention and treatment of SARS-CoV-2 infection in pediatric populations.
Individuals who receive a third mRNA vaccine dose show enhanced protection against severe COVID-19, but little is known about the impact of breakthrough infections on memory responses. Here, we examine the memory antibodies that develop after a third or fourth antigenic exposure by Delta or Omicron BA.1 infection, respectively. A third exposure to antigen by Delta breakthrough increases the number of memory B cells that produce antibodies with comparable potency and breadth to a third mRNA vaccine dose. A fourth antigenic exposure with Omicron BA.1 infection increased variant-specific plasma antibody and memory B cell responses. However, the fourth exposure did not increase the overall frequency of memory B cells or their general potency or breadth compared to a third mRNA vaccine dose. In conclusion, a third antigenic exposure by Delta infection elicits strain-specific memory responses and increases in the overall potency and breadth of the memory B cells. In contrast, the effects of a fourth antigenic exposure with Omicron BA.1 are limited to increased strain-specific memory with little effect on the potency or breadth of memory B cell antibodies. The results suggest that the effect of strain-specific boosting on memory B cell compartment may be limited.
September 21, 2022
Impaired immune response drives age-dependent severity of COVID-19
Severity of COVID-19 shows an extraordinary correlation with increasing age. We generated a mouse model for severe COVID-19 and show that the age-dependent disease severity is caused by the disruption of a timely and well-coordinated innate and adaptive immune response due to impaired interferon (IFN) immunity. Aggravated disease in aged mice was characterized by a diminished IFN-γ response and excessive virus replication. Accordingly, adult IFN-γ receptor-deficient mice phenocopied the age-related disease severity, and supplementation of IFN-γ reversed the increased disease susceptibility of aged mice. Further, we show that therapeutic treatment with IFN-λ in adults and a combinatorial treatment with IFN-γ and IFN-λ in aged Ifnar1−/− mice was highly efficient in protecting against severe disease. Our findings provide an explanation for the age-dependent disease severity and clarify the nonredundant antiviral functions of type I, II, and III IFNs during SARS-CoV-2 infection in an age-dependent manner. Our data suggest that highly vulnerable individuals could benefit from immunotherapy combining IFN-γ and IFN-λ.
September 20, 2022
Omicron BA.2 breakthrough infection enhances cross-neutralization of BA.2.12.1 and BA.4/BA.5
BNT162b2-vaccinated individuals after Omicron BA.1 breakthrough infection have strong serum neutralizing activity against Omicron BA.1, BA.2, and previous SARS-CoV-2 variants of concern (VOCs), yet less against the highly contagious Omicron sublineages BA.4 and BA.5 that have displaced previous variants. As the latter sublineages are derived from Omicron BA.2, we characterized serum neutralizing activity of COVID-19 mRNA vaccine triple-immunized individuals who experienced BA.2 breakthrough infection. We demonstrate that sera of these individuals have broadly neutralizing activity against previous VOCs as well as all tested Omicron sublineages, including BA.2 derived variants BA.2.12.1, BA.4/BA.5. Furthermore, applying antibody depletion we showed that neutralization of BA.2 and BA.4/BA.5 sublineages by BA.2 convalescent sera is driven to a significant extent by antibodies targeting the N-terminal domain (NTD) of the spike glycoprotein. However, neutralization by Omicron BA.1 convalescent sera depends exclusively on antibodies targeting the receptor binding domain (RBD). These findings suggest that exposure to Omicron BA.2, in contrast to BA.1 spike glycoprotein, triggers significant NTD specific recall responses in vaccinated individuals and thereby enhances the neutralization of BA.4/BA.5 sublineages. Given the current epidemiology with a predominance of BA.2 derived sublineages like BA.4/BA.5 and rapidly ongoing evolution, these findings helped to inform development of our Omicron BA.4/BA.5-adapted vaccine.
High relative incidence of vascular events soon after COVID-19 diagnosis declines more rapidly for arterial thromboses than VTEs. However, incidence remains elevated up to 49 weeks after COVID-19 diagnosis. These results support policies to prevent severe COVID-19 by means of COVID-19 vaccines, early review after discharge, risk factor control, and use of secondary preventive agents in high-risk patients.
September 19, 2022
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires fusion of viral and host membranes, mediated by the viral spike glycoprotein (S). Due to the importance of viral membrane fusion, S has been a popular target for developing vaccines and therapeutics. We discovered a simple peptide that inhibits infection by all major variants of SARS-CoV-2 with nanomolar efficacies. In marked contrast, widely used shorter peptides that lack a key N-terminal extension are about 100 times less potent than this peptide. Our results suggest that a simple peptide with a suitable sequence can be a potent and cost-effective therapeutic against coronavirus disease 2019, and they provide new insights into the virus entry mechanism.
September 16, 2022
A Bivalent Omicron-Containing Booster Vaccine against Covid-19
The bivalent omicron-containing vaccine mRNA-1273.214 elicited neutralizing antibody responses against omicron that were superior to those with mRNA-1273, without evident safety concerns.
Omicron sublineage BA.2.75.2 exhibits extensive escape from neutralising antibodies
Several sublineages of omicron have emerged with additional mutations that may afford further antibody evasion. Here, we characterise the sensitivity of emerging omicron sublineages BA.2.75.2, BA.4.6, and BA.2.10.4 to antibody-mediated neutralisation, and identify extensive escape by BA.2.75.2. BA.2.75.2 was resistant to neutralisation by Evusheld (tixagevimab + cilgavimab), but remained sensitive to bebtelovimab. In recent serum samples from blood donors in Stockholm, Sweden, BA.2.75.2 was neutralised, on average, five-fold less potently than BA.5, representing the most neutralisation resistant variant evaluated to date. These data raise concerns that BA.2.75.2 may effectively evade humoral immunity in the population.
In-hospital mortality among patients hospitalized primarily for COVID-19 decreased from 15.1% (Delta period) to 4.9% (later Omicron period; April–June 2022), despite high-risk patient groups representing a larger proportion of hospitalizations. During the later Omicron period, the majority of in-hospital deaths occurred among adults aged ≥65 years (81.9%) and persons with three or more underlying medical conditions (73.4%).
September 15, 2022
Older people who were infected with COVID-19 show a substantially higher risk – as much as 50% to 80% higher than a control group – of developing Alzheimer’s disease within a year, according to a study of more than 6 million patients 65 and older. In a study published in the Journal of Alzheimer’s Disease, researchers report that people 65 and older who contracted COVID-19 were more prone to developing Alzheimer’s disease in the year following their COVID diagnosis. And the highest risk was observed in women at least 85 years old.
Two-Year Health Outcomes in Hospitalized COVID-19 Survivors in China
These findings suggest that prolonged symptoms may persist in a proportion of COVID-19 survivors for 2 years after SARS-CoV-2 infection.
COVID-19 patients exhibit unique transcriptional signatures indicative of disease severity
Overall, we have identified immune profiles of severe COVID-19 patients associated with full recovery from disease or increased risk of mortality. We propose that these differences in COVID Group 1 and Group 2 patients could be employed to better allocate healthcare resources and design targeted treatment plans to better care for individuals who are at the greatest risk of worse outcomes. Whereas optimal medical care and appropriate ventilator management may be sufficient in patients with immune profiles similar to COVID Group 1, patients with immune profiles similar to COVID Group 2 could benefit from more aggressive therapeutic intervention targeting the dysregulated innate immune response. In particular, drugs targeting Type I IFNs, cytokines, such as IL6 or TNF, or myeloid chemokines such as IP-10 or MCP1 could be effective treatments for these individuals. Our work highlights the heterogeneity among severe cases of COVID-19 and the need for better characterization of hospitalized individuals to determine effective strategies to mitigate pathogenic immune processes that are dysregulated in the most at-risk patients. Furthermore, infected individuals with the potential to progress to severe disease should be identified as early as possible to allow for better resource allocation and early individualized therapies.
Although our results await confirmation with authentic virus and primary cells, BA.2.75 might be more adept than BA.2 at infecting the lower airways and inducing cell–cell fusion, which could indicate an elevated intrinsic pathogenic potential. Moreover, we identified bebtelovimab (also known as LYCoV-1404) and the cilgavimab–tixagevimab antibody combination as treatments for BA.2.75-infected individuals. The observation that BA.2.75 and BA.4/BA.5 display lower neutralisation sensitivity compared with BA.2 suggests that this trait might enable them to outcompete BA.2 in subpopulations with vaccination or infection-induced immunity. Finally, our data confirm and extend the findings of two recent studies and provide evidence that three vaccine doses are required to induce potent neutralising activity against BA.2.75, similar to what has been shown for other omicron sublineages.
Rebound of SARS-CoV-2 Infection after Nirmatrelvir–Ritonavir Treatment
In the EPIC-HR (Evaluation of Protease Inhibition for Covid-19 in High-Risk Patients) trial of nirmatrelvir–ritonavir, which was conducted during a period when the B.1.617.2 (delta) variant was predominant in the United States, investigators noted the occurrence of virologic rebound in some patients regardless of whether they had received antiviral treatment. In contrast, in a study involving National Basketball Association personnel who were under infection surveillance and who were not treated with nirmatrelvir–ritonavir, Ct values of less than 30 were not detected for the omicron variant between day 11 and day 15. Here, our evaluation includes a convenience sample in which 5 of 13 cases occurred within two families, which suggests that rebound after nirmatrelvir–ritonavir therapy is not uncommon. Additional data are needed to determine the cause, frequency, duration, and spectrum of rebound symptoms along with the relation to antiviral treatment. During rebound, the findings of a higher viral load, the ease of viral culture, and possible viral transmission suggest that patients are likely to be contagious during the rebound period.
September 14, 2022
The epidemiology of long COVID in US adults two years after the start of the US SARS-CoV-2 pandemic
We observed a high burden of long COVID and substantial variability in prevalence of SARS-CoV-2. Population-based surveys are an important surveillance tool and supplement to ongoing efforts to monitor long COVID.
SARS-CoV-2 has extensively mutated creating variants of concern (VOC) resulting in global infection surges. The Omicron VOC reinfects individuals exposed to earlier variants of SARS-CoV-2 at a higher frequency than previously seen for non-Omicron VOC. An analysis of the sub-lineages associated with an Omicron primary infection and Omicron reinfection reveals that the incidence of Omicron-Omicron reinfections is occurring over a shorter time interval than seen after a primary infection with a non-Omicron VOC. Our analysis suggests that a single infection from SARS-CoV-2 may not generate the protective immunity required to defend against reinfections from emerging Omicron lineages. This analysis was made possible by Next-generation sequencing (NGS), specifically of a Danish cohort with clinical metadata on both infections occurring in the same individual. We suggest that the continuation of COVID-19 NGS and inclusion of clinical metadata is necessary to ensure effective surveillance of SARS-CoV-2 genomics, assist in treatment and vaccine development, and guide public health recommendations.
The Lancet Commission on lessons for the future from the COVID-19 pandemic
As of May 31, 2022, there were 6·9 million reported deaths and 17·2 million estimated deaths from COVID-19, as reported by the Institute for Health Metrics and Evaluation (IHME; throughout the report, we rely on IHME estimates of infections and deaths; note that the IHME gives an estimated range, and we refer to the mean estimate). This staggering death toll is both a profound tragedy and a massive global failure at multiple levels. Too many governments have failed to adhere to basic norms of institutional rationality and transparency, too many people—often influenced by misinformation—have disrespected and protested against basic public health precautions, and the world's major powers have failed to collaborate to control the pandemic.
Effectiveness and Durability of the BNT162b2 Vaccine against Omicron Sublineages in South Africa
Thus, after either two doses or three doses of the BNT162b2 vaccine, we found rapid waning of vaccine effectiveness against the current sublineages of the omicron variant with respect to protection against hospitalization. Our data indicate that boosting maintains vaccine effectiveness against severe disease caused by the current omicron sublineages, although the evidence of rapid waning of durability indicates the need for regular boosting as early as 4 months after the last dose or the need for vaccines to incorporate variants of concern to maintain protection.
Anti-Spike Mucosal IgA Protection against SARS-CoV-2 Omicron Infection
Taken together, these findings suggest that wild-type SARS-CoV-2 spike-specific mucosal IgA is protective against omicron infection. Further studies are warranted to determine whether vaccines that induce a combination of mucosal and systemic immune responses would confer stronger protection than intramuscular vaccines.
As additional SARS-CoV-2 variants evolve, vaccines that maintain efficacy across these variants become increasingly important. Here, Hajnik et al. tested whether an mRNA vaccine encoding the more conserved nucleocapsid (N) protein of SARS-CoV-2 can elicit responses that protect against SARS-CoV-2 challenge in vivo. mRNA-N vaccination alone elicited immune responses that could control SARS-CoV-2. Furthermore, combining mRNA-N vaccination with an mRNA vaccine encoding the spike protein (mRNA-S+N) induced better viral control than mRNA-S vaccination alone, including against the Omicron variant. Thus, incorporating the N protein into SARS-CoV-2 vaccines may promote protection against existing and future variants.
September 13, 2022
Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants including BA.4 and BA.5
After the global spread of the SARS-CoV-2 Omicron BA.2, some BA.2 subvariants, including BA.2.9.1, BA.2.11, BA.2.12.1, BA.4 and BA.5, emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these BA.2 subvariants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1/2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. We further provided the structure of BA.4/5 spike receptor-binding domain that binds to human ACE2 and considered how the substitutions in BA.4/5 spike play roles in ACE2 binding and immune evasion. Moreover, experiments using hamsters suggested that BA.4/5 is more pathogenic than BA.2. Our multiscale investigations suggest that the risk of BA.2 subvariants, particularly BA.4/5, to global health is greater than that of original BA.2.
The emergence of SARS-CoV-2 variants in the Omicron lineage with large numbers of substitutions in the spike protein that can evade antibody neutralization has resulted in diminished vaccine efficacy and persistent transmission. One strategy to broaden vaccine-induced immunity is to administer bivalent vaccines that encode for spike proteins from both historical and newly-emerged variant strains. Here, we evaluated the immunogenicity and protective efficacy of two bivalent vaccines that recently were authorized for use in Europe and the United States and contain two mRNAs encoding Wuhan-1 and either BA.1 (mRNA-1273.214) or BA.4/5 (mRNA-1273.222) spike proteins. As a primary immunization series in BALB/c mice, both bivalent vaccines induced broader neutralizing antibody responses than the constituent monovalent vaccines (mRNA-1273 [Wuhan-1], mRNA-1273.529 [BA.1], and mRNA-1273-045 [BA.4/5]). When administered to K18-hACE2 transgenic mice as a booster at 7 months after the primary vaccination series with mRNA-1273, the bivalent vaccines induced greater breadth and magnitude of neutralizing antibodies compared to an mRNA-1273 booster. Moreover, the response in bivalent vaccine-boosted mice was associated with increased protection against BA.5 infection and inflammation in the lung. Thus, boosting with bivalent Omicron-based mRNA-1273.214 or mRNA-1273.222 vaccines enhances immunogenicity and protection against currently circulating SARS-CoV-2 strains.
This study, based on comprehensive health care administrative data, provides evidence that a fourth mRNA vaccine dose confers additional sustained protection against hospitalization and severe disease from COVID-19 in an elderly Asian population during Omicron variant epidemic.
September 12, 2022
SARS-CoV-2 in immunocompromised individuals
Immunocompromised individuals and particularly those with hematologic malignancies are at increased risk for SARS-CoV-2-associated morbidity and mortality due to immunologic deficits that limit prevention, treatment, and clearance of the virus. Understanding the natural history of viral infections in people with impaired immunity due to underlying conditions, immunosuppressive therapy, or a combination thereof has emerged as a critical area of investigation during the COVID-19 pandemic. Studies focused on these individuals have provided key insights into aspects of innate and adaptive immunity underlying both the anti-viral immune response and excess inflammation in the setting of COVID-19. This review presents what is known about distinct states of immunologic vulnerability to SARS-CoV-2 and how this information can be harnessed to improve prevention and treatment strategies for immunologically high-risk populations.
September 9, 2022
Studying 446 people hospitalised for COVID-19, we show durable nasal and plasma IgG responses to ancestral (B.1 lineage) SARS-CoV-2, Delta and Omicron (BA.1) variants up to 12 months after infection. Nasal antibody induced by infection with pre-Omicron variants, bind Omicron virus in vitro better than plasma antibody. Although nasal and plasma IgG responses were enhanced by vaccination, Omicron binding responses did not reach levels equivalent to responses for ancestral SARS-CoV-2. Using paired plasma and nasal samples collected approximately 12 months after infection, we show that nasal IgA declines and shows a minimal response to vaccination whilst plasma antibody responses to S antigen are well maintained and boosted by vaccination.
COVID-19 vaccines used in humans are highly effective in limiting disease and death caused by the SARS-CoV-2 virus, yet improved vaccines that provide greater protection at mucosal surfaces, which could reduce break-through infections and subsequent transmission, are still needed. Here we show that intranasal (I.N.) vaccination with the receptor binding domain of Spike antigen of SARS-CoV-2 (S-RBD) in combination with the mucosal adjuvant mastoparan-7 improved systemic T cell responses compared to an equivalent dose of antigen delivered by the sub-cutaneous (S.C.) route, adjuvanted by either M7 or the gold-standard adjuvant, alum. T cell phenotypes induced by I.N. vaccine administration included enhanced polyfunctionality (combined IFN-γ and TNF expression) and greater numbers of T central memory (TCM) cells. These phenotypes were T cell-intrinsic and could be recalled in the lungs and/or brachial LNs upon antigen challenge after adoptive T cell transfer to naïve recipients. Furthermore, mucosal vaccination induced antibody responses that were similarly effective in neutralizing the binding of the parental strain of S-RBD to its ACE2 receptor, but showed greater cross-neutralizing capacity against multiple variants of concern (VOC), compared to S.C. vaccination. These results highlight the role of nasal vaccine administration in imprinting an immune profile associated with long-term T cell retention and diversified neutralizing antibody responses, which could be applied to improve vaccines for COVID-19 and other infectious diseases.
September 8, 2022
There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children generally develop less severe disease than older adults, which is unusual for a respiratory disease. However, some children can develop serious complications from COVID-19, such as multisystem inflammatory syndrome in children (MIS-C) and Long Covid, even after mild or asymptomatic COVID-19. Why this occurs in some and not others is an important question. Moreover, when children do contract COVID-19, understanding their role in transmission, especially in schools and at home, is crucial to ensuring effective mitigation measures. Therefore, in addition to nonpharmaceutical interventions, such as improved ventilation, there is a strong case to vaccinate children so as to reduce possible long-term effects from infection and to decrease transmission. But questions remain about whether vaccination might skew immune responses to variants in the long term. As the experts discuss below, more is being learned about these important issues, but much more research is needed to understand the long-term effects of COVID-19 in children.
COVID-19 infection and transmission includes complex sequence diversity
SARS-CoV-2 whole genome sequencing has played an important role in documenting the emergence of polymorphisms in the viral genome and its continuing evolution during the COVID-19 pandemic. Here we present data from over 360 patients to characterize the complex sequence diversity of individual infections identified during multiple variant surges (e.g., Alpha and Delta). Across our survey, we observed significantly increasing SARS-CoV-2 sequence diversity during the pandemic and frequent occurrence of multiple biallelic sequence polymorphisms in all infections. This sequence polymorphism shows that SARS-CoV-2 infections are heterogeneous mixtures. Convention for reporting microbial pathogens guides investigators to report a majority consensus sequence. In our study, we found that this approach would under-report sequence variation in all samples tested. As we find that this sequence heterogeneity is efficiently transmitted from donors to recipients, our findings illustrate that infection complexity must be monitored and reported more completely to understand SARS-CoV-2 infection and transmission dynamics. Many of the nucleotide changes that would not be reported in a majority consensus sequence have now been observed as lineage defining SNPs in Omicron BA.1 and/or BA.2 variants. This suggests that minority alleles in earlier SARS-CoV-2 infections may play an important role in the continuing evolution of new variants of concern.
Understanding myalgic encephalomyelitis
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) presents as a range of symptoms that affect multiple organ systems. Enteric dysbiosis, neurological and immune dysfunction, as well as impaired mitochondrial function are implicated in the pathomechanism of ME/CFS. These symptoms also occur in Long Covid, although with differing prevalence.
September 7, 2022
Protection against SARS-CoV-2 transmission by a parenteral prime—Intranasal boost vaccine strategy
This study suggests that parenteral-prime mucosal boost is an effective strategy for protecting against SARS-CoV-2 infection and highlights that protection against virus transmission may be obtained despite incomplete clearance of virus from the upper respiratory tract. It should be noted that protection against onward transmission was not compared to standard parenteral prime-boost, which should be a focus for future studies.
Durability of Booster mRNA Vaccine against SARS-CoV-2 BA.2.12.1, BA.4, and BA.5 Subvariants
The decrease in booster durability appeared to be slower than the decrease that was previously reported for two doses of mRNA vaccine alone. Although the rate of booster neutralizing-antibody decay was similar among variants, the omicron subvariants, especially BA.4/5, had substantial neutralization resistance. Our observed trends are consistent with the waning of vaccine protection and natural immunity, and our data suggest that both SARS-CoV-2 variant evolution and waning neutralizing-antibody titers reduce booster-induced immune protection. Our anecdotal experience in two participants indicates that a fourth dose of vaccine may be effective. A variant-specific booster may become necessary as new variants evolve.
September 6, 2022
Resistance of SARS-CoV-2 Omicron Subvariant BA.4.6 to Antibody Neutralization
SARS-CoV-2 Omicron subvariants BA.4.6, BA.4.7, and BA.5.9 have recently emerged, and BA.4.6 appears to be expanding even in the presence of BA.5 that is globally dominant. Compared to BA.5, these new subvariants harbor a mutation at R346 residue in the spike glycoprotein, raising concerns for further antibody evasion. We compared the viral receptor binding affinity of the new Omicron subvariants with BA.5 by surface plasmon resonance. We also performed VSV-based pseudovirus neutralization assays to evaluate their antigenic properties using sera from individuals who received three doses of a COVID-19 mRNA vaccine (boosted) and patients with BA.1 or BA.2 breakthrough infection, as well as using a panel of 23 monoclonal antibodies (mAbs). Compared to the BA.5 subvariant, BA.4.6, BA.4.7, and BA.5.9 showed similar binding affinities to hACE2 and exhibited similar resistance profiles to boosted and BA.1 breakthrough sera, but BA.4.6 was slightly but significantly more resistant than BA.5 to BA.2 breakthrough sera. Moreover, BA.4.6, BA.4.7, and BA.5.9 showed heightened resistance over to a class of mAbs due to R346T/S/I mutation. Notably, the authorized combination of tixagevimab and cilgavimab completely lost neutralizing activity against these three subvariants. The loss of activity of tixagevimab and cilgavimab against BA.4.6 leaves us with bebtelovimab as the only therapeutic mAb that has retained potent activity against all circulating forms of SARS-CoV-2. As the virus continues to evolve, our arsenal of authorized mAbs may soon be depleted, thereby jeopardizing the wellbeing of millions of immunocompromised persons who cannot robustly respond to COVID-19 vaccines.
An estimated 17.3% (95% CI 14.9, 19.8) of respondents had SARS-CoV-2 infection during the two-week study period–equating to 44 million cases as compared to 1.8 million per the CDC during the same time period. SARS-CoV-2 prevalence was higher among those 18-24 years old (aPR 2.2, 95% CI 1.8, 2.7) and among non-Hispanic Black (aPR 1.7, 95% CI 1.4, 2.2) and Hispanic (aPR 2.4, 95% CI 2.0, 2.9). SARS-CoV-2 prevalence was also higher among those with lower income (aPR 1.9, 95% CI 1.5, 2.3), lower education (aPR 3.7 95% CI 3.0,4.7), and those with comorbidities (aPR 1.6, 95% CI 1.4, 2.0). An estimated 21.5% (95% CI 18.2, 24.7) of respondents with a SARS-CoV-2 infection more than 4 weeks prior reported long COVID symptoms. The inequitable distribution of SARS-CoV-2 prevalence during the BA.5 surge will likely drive inequities in the future burden of long COVID.
Neutralisation sensitivity of the SARS-CoV-2 omicron BA.2.75 sublineage
Variants of SARS-CoV-2 with reduced sensitivity to neutralising antibodies can pose a challenge to immunity induced by vaccination or infection and can render therapeutic monoclonal antibodies ineffective. Our results suggest that the mutations in the spike protein of the BA.2.75 sublineage decrease susceptibility to vaccine-induced neutralising activity compared with BA.2, albeit to a lesser extent than the mutations present in BA.4/5. Moreover, BA.2.75 showed an overall higher sensitivity to SARS-CoV-2 neutralising monoclonal antibodies in advanced development, including antibodies currently in clinical use. Although our analysis of vaccinee sera was limited to a single post-booster timepoint, our results and those of others suggest that antibody escape is an overall less pronounced characteristic of BA.2.75 compared with BA.4/5. Thus, additional features favouring viral expansion beyond vaccine escape might be required for BA.2.75 to gain a growth advantage over BA.4/5.
September 5, 2022
Long-term cardiac pathology in individuals with mild initial COVID-19 illness
Cardiac symptoms are increasingly recognized as late complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in previously well individuals with mild initial illness, but the underlying pathophysiology leading to long-term cardiac symptoms remains unclear. In this study, we conducted serial cardiac assessments in a selected population of individuals with Coronavirus Disease 2019 (COVID-19) with no previous cardiac disease or notable comorbidities by measuring blood biomarkers of heart injury or dysfunction and by performing magnetic resonance imaging. Baseline measurements from 346 individuals with COVID-19 (52% females) were obtained at a median of 109 days (interquartile range (IQR), 77–177 days) after infection, when 73% of participants reported cardiac symptoms, such as exertional dyspnea (62%), palpitations (28%), atypical chest pain (27%) and syncope (3%). Symptomatic individuals had higher heart rates and higher imaging values or contrast agent accumulation, denoting inflammatory cardiac involvement, compared to asymptomatic individuals. Structural heart disease or high levels of biomarkers of cardiac injury or dysfunction were rare in symptomatic individuals. At follow-up (329 days (IQR, 274–383 days) after infection), 57% of participants had persistent cardiac symptoms. Diffuse myocardial edema was more pronounced in participants who remained symptomatic at follow-up as compared to those who improved. Female gender and diffuse myocardial involvement on baseline imaging independently predicted the presence of cardiac symptoms at follow-up. Ongoing inflammatory cardiac involvement may, at least in part, explain the lingering cardiac symptoms in previously well individuals with mild initial COVID-19 illness.
Antigenic characterization of the SARS-CoV-2 Omicron subvariant BA.2.75
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.2.75 emerged recently and appears to be spreading. It has nine mutations in spike compared with the currently circulating BA.2, raising concerns that it may further evade vaccine-elicited and therapeutic antibodies. We found BA.2.75 to be moderately more neutralization resistant to sera from vaccinated/boosted individuals than BA.2 (1.8-fold), similar to BA.2.12.1 (1.1-fold), but more neutralization sensitive than BA.4/5 (0.6-fold). Relative to BA.2, BA.2.75 showed heightened resistance to class 1 and class 3 monoclonal antibodies targeting the spike-receptor-binding domain while gaining sensitivity to class 2 antibodies. Resistance was largely conferred by G446S and R460K mutations. BA.2.75 was slightly resistant (3.7-fold) to bebtelovimab, a therapeutic antibody with potent activity against all Omicron subvariants. BA.2.75 also exhibited a higher binding affinity to host receptor ACE2 than other Omicron subvariants. BA.2.75 provides further insight into SARS-CoV-2 evolution as it gains transmissibility while incrementally evading antibody neutralization.
September 1, 2022
Nirmatrelvir Use and Severe Covid-19 Outcomes during the Omicron Surge
Among patients 65 years of age or older, the rates of hospitalization and death due to Covid-19 were significantly lower among those who received nirmatrelvir than among those who did not. No evidence of benefit was found in younger adults.
New Omicron-specific vaccines offer similar protection to existing boosters
Most of these trials found that the updated vaccines — based not only on Omicron, but also on older variants, including Beta — performed a bit better in terms of this measure than the original vaccines did. “This is a clearly superior booster,” Stephen Hoge, the president of pharmaceutical firm Moderna, told investors on 8 June when touting such results from the company’s BA.1-based bivalent vaccine.
September 2022
The Impacts of Covid-19 Illnesses on Workers
We show that Covid-19 illnesses persistently reduce labor supply. Using an event study, we estimate that workers with week-long Covid-19 work absences are 7 percentage points less likely to be in the labor force one year later compared to otherwise-similar workers who do not miss a week of work for health reasons. Our estimates suggest Covid-19 illnesses have reduced the U.S. labor force by approximately 500,000 people (0.2 percent of adults) and imply an average forgone earnings per Covid-19 absence of at least $9,000, about 90 percent of which reflects lost labor supply beyond the initial absence week.
The onset, progression, and symptom profile of post COVID-19 condition patients have considerable overlap with ME/CFS. Considering the large scope and range of pro-inflammatory effects of this virus, it is reasonable to expect development of post COVID-19 clinical complications in a proportion of the affected population. There are reports of a later debilitating syndrome onset three months post COVID-19 infection (often described as long-COVID-19), marked by the presence of fatigue, headache, cognitive dysfunction, post-exertional malaise, orthostatic intolerance, and dyspnoea. Acute inflammation, oxidative stress, and increased levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNFα), have been reported in SARS-CoV-2 infected patients. Longitudinal monitoring of post COVID-19 patients is warranted to understand the long-term effects of SARS-CoV-2 infection and the pathomechanism of post COVID-19 condition.
August 30, 2022
A subset of patients has long-lasting symptoms after mild to moderate Coronavirus disease 2019 (COVID-19). In a prospective observational cohort study, we analyze clinical and laboratory parameters in 42 post-COVID-19 syndrome patients (29 female/13 male, median age 36.5 years) with persistent moderate to severe fatigue and exertion intolerance six months following COVID-19. Further we evaluate an age- and sex-matched postinfectious non-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome cohort comparatively. Most post-COVID-19 syndrome patients are moderately to severely impaired in daily live. 19 post-COVID-19 syndrome patients fulfill the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome. Disease severity and symptom burden is similar in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome and non-COVID-19/myalgic encephalomyelitis/chronic fatigue syndrome patients. Hand grip strength is diminished in most patients compared to normal values in healthy. Association of hand grip strength with hemoglobin, interleukin 8 and C-reactive protein in post-COVID-19 syndrome/non-myalgic encephalomyelitis/chronic fatigue syndrome and with hemoglobin, N-terminal prohormone of brain natriuretic peptide, bilirubin, and ferritin in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome may indicate low level inflammation and hypoperfusion as potential pathomechanisms.
August 26, 2022
Increased hospitalization rates among adults aged ≥65 years compared with rates among younger adults were most pronounced during the Omicron BA.2–predominant period. Among hospitalized nonpregnant patients, 44.1% had received primary vaccination and ≥1 booster or additional dose. Hospitalization rates among unvaccinated adults were approximately triple those of vaccinated adults.
August 22, 2022
In this systematic review and meta-analysis of 141 articles, the pooled incubation period was 6.57 days. The incubation periods of COVID-19 caused by the Alpha, Beta, Delta, and Omicron variants were 5.00, 4.50, 4.41, and 3.42 days, respectively.
Regular physical activity seems to be related to a lower likelihood of adverse COVID-19 outcomes. Our findings highlight the protective effects of engaging in sufficient physical activity as a public health strategy, with potential benefits to reduce the risk of severe COVID-19. Given the heterogeneity and risk of publication bias, further studies with standardised methodology and outcome reporting are now needed.
he emergent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants complicate the battle to halt the coronavirus disease 2019 (COVID-19) pandemic. The currently approved vaccines typically express native full-length S or preS-2P. Here, we show that HexaPro is superior to 2P or the native full-length S protein as a SARS-CoV-2 vaccine immunogen. HexaPro is expressed more efficiently and induces more robust SARS-CoV-2 specific antibody and Th1-biased T cell immune responses. Antibodies induced by HexaPro also neutralize SARS-CoV-2 variants two- to fourfold more efficiently than those induced by preS-2P. By comparing different immunization doses, we found that HexaPro is more immunogenic and protective than 2P. This work highlights the importance of using HexaPro in the development of next generation COVID-19 vaccines because of its broad protection against SARS-CoV-2 variants.
August 20, 2022
Oral Nirmatrelvir and Ritonavir in Non-hospitalized Vaccinated Patients with Covid-19
Treatment with NMV-r in non-hospitalized vaccinated patients with Covid-19 was associated with a reduced likelihood of emergency room visits, hospitalization, or death. Complications and overall resource utilization were also decreased.
August 19, 2022
Among children aged 5–11 years, local and systemic reactions were reported to v-safe with similar frequency after doses 2 and 3; specific reactions differed in severity. Vaccine administration errors were the most common events reported to the Vaccine Adverse Event Reporting System. No reports of myocarditis or death after receipt of dose 3 were received.
Public transportation industries in California experienced cumulative COVID-19 outbreak incidence and mortality rates 1.5 times as high as that for all industries; outbreak incidence was 5.2 times as high, and mortality was 1.8 times as high in bus and urban transit industries as in all industries.
August 18, 2022
Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19
A total of 1431 patients underwent randomization; of these patients, 1323 were included in the primary analysis. The median age of the patients was 46 years; 56% were female (6% of whom were pregnant), and 52% had been vaccinated. The adjusted odds ratio for a primary event was 0.84 (95% confidence interval [CI], 0.66 to 1.09; P=0.19) with metformin, 1.05 (95% CI, 0.76 to 1.45; P=0.78) with ivermectin, and 0.94 (95% CI, 0.66 to 1.36; P=0.75) with fluvoxamine. In prespecified secondary analyses, the adjusted odds ratio for emergency department visit, hospitalization, or death was 0.58 (95% CI, 0.35 to 0.94) with metformin, 1.39 (95% CI, 0.72 to 2.69) with ivermectin, and 1.17 (95% CI, 0.57 to 2.40) with fluvoxamine. The adjusted odds ratio for hospitalization or death was 0.47 (95% CI, 0.20 to 1.11) with metformin, 0.73 (95% CI, 0.19 to 2.77) with ivermectin, and 1.11 (95% CI, 0.33 to 3.76) with fluvoxamine. None of the three medications that were evaluated prevented the occurrence of hypoxemia, an emergency department visit, hospitalization, or death associated with Covid-19.
Time to Stop Using Ineffective Covid-19 Drugs
Prescribing nonefficacious treatments is not a neutral or harmless option. In addition to denying patients the appropriate treatment, such prescribing can lead to side effects without any therapeutic benefit and to drug shortages for patients who need the medications for other conditions. Hence, it is important to have reliable evidence of nonefficacy and to have journals publish such studies. It is also important that multiple rigorous randomized, controlled trials be performed to provide unequivocal evidence on the efficacy of new treatments, as the Covid-19 experience has shown.
August 17, 2022
How much virus does a person with COVID exhale? New research has answers
People infected with the highly transmissible Alpha, Delta and Omicron variants of SARS-CoV-2 spew out higher amounts of virus than do those infected with other variants, according to a study1. Furthermore, individuals who contract COVID-19 after vaccination, and even after a booster dose, still shed virus into the air.
This analysis of 2-year retrospective cohort studies of individuals diagnosed with COVID-19 showed that the increased incidence of mood and anxiety disorders was transient, with no overall excess of these diagnoses compared with other respiratory infections. In contrast, the increased risk of psychotic disorder, cognitive deficit, dementia, and epilepsy or seizures persisted throughout. The differing trajectories suggest a different pathogenesis for these outcomes. Children have a more benign overall profile of psychiatric risk than do adults and older adults, but their sustained higher risk of some diagnoses is of concern. The fact that neurological and psychiatric outcomes were similar during the delta and omicron waves indicates that the burden on the health-care system might continue even with variants that are less severe in other respects. Our findings are relevant to understanding individual-level and population-level risks of neurological and psychiatric disorders after SARS-CoV-2 infection and can help inform our responses to them.
Neuropsychiatric sequelae of COVID-19: long-lasting, but not uniform
In the general population, individuals who have had COVID-19 have been found to have substantial deficits on computerised cognitive batteries. Taquet and colleagues found that this deficit does indeed seem to translate into an increased risk of a diagnosis of dementia. However, dementia has an insidious onset and the cohort is likely to have had some participants with undiagnosed or subclinical cases at baseline. Although concerning, the findings regarding psychosis and dementia need replication in a cohort in which there is more thorough ascertainment of case status.
Rapid waning of protection induced by prior BA.1/BA.2 infection against BA.5 infection
SARS-CoV-2 omicron subvariants BA.1 and BA.2 became dominant in many countries in early 2022. These subvariants are now being displaced by BA.4 and BA.5. While natural infection with BA.1/BA.2 provides some protection against BA.4/BA.5 infection, the duration of this protection remains unknown. We used the national Portuguese COVID-19 registry to investigate the waning of protective immunity conferred by prior BA.1/BA.2 infection towards BA.5. We divided the individuals infected during the period of BA.1/BA.2 dominance (>90% of sample isolates) in successive 15-day intervals and determined the risk of subsequent infection with BA.5 over a fixed period. Compared with uninfected people, one previous infection conferred substantial protection against BA.5 re-infection at 3 months (RR=0.12; 95% CI: 0.11-0.12). However, although still significant, the protection was reduced by two-fold at 5 months post-infection (RR=0.24; 0.23-0.24). These results should be interpreted in the context of vaccine breakthrough infections, as the vaccination coverage in the individuals included in the analyses is >98% since the end of 2021. This waning of protection following BA.1/BA.2 infection highlights the need to assess the stability and durability of immune protection induced with the adapted vaccines (based on BA.1) over time.
Despite the remarkable efficacy of COVID-19 vaccines, waning immunity and the emergence of SARS-CoV-2 variants such as Omicron represents a global health challenge. Here, we present data from a study in nonhuman primates demonstrating durable protection against the Omicron BA.1 variant induced by a subunit SARS-CoV-2 vaccine comprising the receptor binding domain of the ancestral strain (RBD-Wu) on the I53-50 nanoparticle adjuvanted with AS03, which was recently authorized for use in individuals 18 years or older. Vaccination induced neutralizing antibody (nAb) titers that were maintained at high concentrations for at least 1 year after two doses, with a pseudovirus nAb geometric mean titer (GMT) of 1978 and a live virus nAb GMT of 1331 against the ancestral strain but not against the Omicron BA.1 variant. However, a booster dose at 6 to 12 months with RBD-Wu or RBD-β (RBD from the Beta variant) displayed on I53-50 elicited high neutralizing titers against the ancestral and Omicron variants. In addition, we observed persistent neutralization titers against a panel of sarbecoviruses, including SARS-CoV. Furthermore, there were substantial and persistent memory T and B cell responses reactive to Beta and Omicron variants. Vaccination resulted in protection against Omicron infection in the lung and suppression of viral burden in the nares at 6 weeks after the final booster immunization. Even at 6 months after vaccination, we observed protection in the lung and rapid control of virus in the nares. These results highlight the durable and cross-protective immunity elicited by the AS03-adjuvanted RBD-I53-50 nanoparticle vaccine.
August 16, 2022
In this retrospective cohort study that included 93 906 patients, hospitalization with COVID-19 before vaccine availability and during vaccine availability was significantly associated with higher 90-day risk of venous thromboembolism (adjusted hazard ratios, 1.60 and 1.89, respectively) vs hospitalization with influenza in 2018-2019, but there was no significant difference in the risk of arterial thromboembolism among those hospitalized with COVID-19 during either period (adjusted hazard ratios, 1.04 and 1.07) vs those hospitalized with influenza.
Blood abnormalities found in people with Long Covid
Long Covid is far from uniform, the new study makes clear—for example, only about 20% to 30% of the study’s patients had very high levels of exhausted T cells. But, “The level of consistency is great” among recent studies probing Long Covid biology, says James Heath, president of the Institute for Systems Biology, an author of the Cell paper that found low cortisol and virus reactivation. He notes that his group’s study examined patients about 3 months after SARS-CoV-2 infection, whereas Iwasaki and Putrino’s cohort was on average more than a year out from their COVID-19.
August 15, 2022
There is a need for safe and effective platform vaccines to protect against COVID-19 and other infectious diseases. In this randomized, double-blinded, placebo-controlled Phase 2/3 trial, we evaluate the safety and efficacy of multi-dose Bacillus Calmette-Guerin (BCG) vaccine for prevention of COVID-19 and other infectious disease in a COVID-19-unvaccinated, at-risk-community-based cohort. The at-risk population are adults with type 1 diabetes. We enrolled 144 subjects and randomized 96 to BCG and 48 to placebo. There were no drop-outs over the 15-month trial. A cumulative incidence of 12.5% of placebo-treated and 1% of BCG-treated participants meets criteria for confirmed COVID-19, yielding an efficacy of 92%. The BCG group also displays fewer infectious disease symptoms and lesser severity, and fewer infectious disease events per patient, including COVID-19. There were no BCG-related systemic adverse events. BCG’s broad-based infection protection suggests that it may provide platform protection against new SARS-CoV-2 variants and other pathogens.
Rapid Increase in Suspected SARS-CoV-2 Reinfections, Clark County, Nevada, USA, December 2021
Genetic differences between SARS-CoV-2 variants raise concerns about reinfection. Public health authorities monitored the incidence of suspected reinfection in Clark County, Nevada, USA, during March 2020–March 2022. Suspected reinfections, defined as a second positive PCR test collected >90 days after an initial positive test, were monitored through an electronic disease surveillance system. We calculated the proportion of all new cases per week that were suspected reinfections and rates per 1,000 previously infected persons by demographic groups. The rate of suspected reinfection remained <2.7% until December 2021, then increased to ≈11%, corresponding with local Omicron variant detection. Reinfection rates were higher among adults 18–50 years of age, women, and minority groups, especially persons identifying as American Indian/Alaska Native. Suspected reinfection became more common in Clark County after introduction of the Omicron variant, and some demographic groups are disproportionately affected. Public health surveillance could clarify the SARS-CoV-2 reinfection burden in communities.
We included 2919 HCWs (median age, 43 years (range, 18-73 years); 749 participants (26%) were infected with SARS-CoV-2. SARS-CoV-2 positivity was 13% in HCWs without patient exposure. For those exposed to patients, positivity was 21% for HCWs using respirator masks and 35% for those using surgical/mixed masks (OR, 0.49; 95% CI, 0.39-0.61), showing an increase for surgical/mixed mask users (OR, 1.21; 95% CI, 1.15-1.28) and respirator mask users (OR, 1.15; 95% CI, 1.05-1.27) across categories of patient exposure (Figure). Variables associated with SARS-CoV-2 infection in multivariable analysis included a positive household contact (OR, 7.79; 95% CI, 5.98-10.15), exposure to patients (OR, 1.20 per category of cumulative contact; 95% CI, 1.14-1.26), respirator use (OR, 0.56; 95% CI, 0.43-0.74), and SARS-CoV-2 vaccination (OR, 0.55; 95% CI, 0.41-0.74) (Table). Similar results were obtained in sensitivity analysis.
The Role of Nightlife Settings in Sustained COVID-19 Transmission
The nightlife setting was the driver of COVID-19 spread, while household and healthcare settings were in the lower course of transmission chains. Surveillance and countermeasures targeting the nightlife setting should be prioritized to disrupt COVID-19 transmission, especially in the early stage of an epidemic.
August 12, 2022
During October 31, 2021–June 11, 2022, 10.7 million test results were voluntarily reported by users of four manufacturers’ self-tests; during that period, 361.9 million laboratory-based and point-of-care test results were reported. Completeness of reporting demographic variables and trends in percent positivity were similar across test types. Self-tests are a valuable risk-reduction tool that can guide individual actions, but they currently offer limited utility in enhancing public health surveillance. Laboratory-based and point-of-care test result data, in combination with other COVID-19 surveillance information, continue to provide strong situational awareness.
By April 29, 2022, a total of 702,686 COVID-19 cases were reported among children and adolescents aged 5–17 years in the state of New York.* Pediatric COVID-19 cases and hospitalizations increased during the 2021–22 school year, driven by transmission of the Omicron variant† (1). In late 2021, during the surge in Omicron BA.1 variant cases, state§ and federal¶ authorities expanded access to self-administered, at-home rapid antigen tests, which can increase a person’s knowledge of their COVID-19 status and guide risk-reduction behaviors. New York government agencies sent millions of these tests to schools for distribution to teachers, students, and staff members. Because results of self-administered, at-home tests are not captured by electronic laboratory reporting (in contrast to health care provider–administered tests at a physician’s office or laboratory that are reported through electronic health records or other means), expanded use of these tests might affect interpretation of trends in reported COVID-19 cases; however, this has yet to be assessed** (2). Furthermore, understanding changes in testing behavior before and after the Omicron variant surge might help public health officials better use available COVID-19 data to guide future policy.
August 11, 2022
To prevent medically significant COVID-19 illness and death, persons must understand their risk, take steps to protect themselves and others with vaccines, therapeutics, and nonpharmaceutical interventions when needed, receive testing and wear masks when exposed, receive testing if symptomatic, and isolate for ≥5 days if infected. Medically significant illness, death, and health care system strain can be reduced through vaccination and therapeutics to prevent severe illness, complemented by use of multiple prevention methods to reduce exposure risk and an emphasis on protecting persons at high risk for severe illness.
As of Nov 4, 2021, 191 360 women aged 15–49 years with known pregnancy status had completed the first vaccine dose survey and 94 937 had completed the second dose survey. 180 388 received one dose and 94 262 received a second dose of an mRNA vaccine, with 5597 pregnant participants receiving dose one and 3108 receiving dose two, and 174 765 non-pregnant participants receiving dose one and 91 131 receiving dose two. Of 6179 included unvaccinated control participants, 339 were pregnant and 5840 were not pregnant. Overall, 226 (4·0%) of 5597 vaccinated pregnant females reported a significant health event after dose one of an mRNA vaccine, and 227 (7·3%) of 3108 after dose two, compared with 11 (3·2%) of 339 pregnant unvaccinated females. Pregnant vaccinated females had an increased odds of a significant health event within 7 days of the vaccine after dose two of mRNA-1273 (adjusted odds ratio [aOR] 4·4 [95% CI 2·4–8·3]) compared with pregnant unvaccinated controls within the past 7 days, but not after dose one of mRNA-1273 or any dose of BNT162b2. Pregnant vaccinated females had decreased odds of a significant health event compared with non-pregnant vaccinated females after both dose one (aOR 0·63 [95% CI 0·55–0·72]) and dose two (aOR 0·62 [0·54–0·71]) of any mRNA vaccination. There were no significant differences in any analyses when restricted to events which led to medical attention.
Morphological, cellular, and molecular basis of brain infection in COVID-19 patients
Neurological symptoms are among the most prevalent of the extrapulmonary complications of COVID-19, affecting more than 30% of patients. In this study, we provide evidence that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is found in the human brain, where it infects astrocytes and to a lesser extent, neurons. We also show that astrocytes are susceptible to SARS-CoV-2 infection through a noncanonical mechanism that involves spike–NRP1 interaction and respond to the infection by remodeling energy metabolism, which in turn, alters the levels of metabolites used to fuel neurons and support neurotransmitter synthesis. The altered secretory phenotype of infected astrocytes then impairs neuronal viability. These features could explain the damage and structural changes observed in the brains of COVID-19 patients.
August 10, 2022
ARS-CoV-2, the causative agent of COVID-19 disease has resulted in the death of millions worldwide since the beginning of the pandemic in December 2019. While much progress has been made to understand acute manifestations of SARS-CoV-2 infection, less is known about post-acute sequelae of COVID-19 (PASC). We investigated the levels of circulating SARS-CoV-2 components, Spike protein and viral RNA, in patients hospitalized with acute COVID-19 and in patients with and without PASC. In hospitalized patients with acute COVID-19 (n=116), we observed a positive correlation of Spike protein with D-dimer, length of hospitalization, and peak WHO score while viral RNA correlated with a tissue injury marker, lactate dehydrogenase (LDH). When comparing patients with post-COVID symptoms (n=33) and patients without (n=14), we found that Spike protein and viral RNA were more likely to be present in patients with PASC and in some cases at higher levels compared to acute COVID-19 patients. We also observed that the percent positivity of circulating viral RNA increased in the PASC positive individuals compared to acute COVID-19 group while Spike protein positivity remained the same. Additionally, we report that part of the circulating Spike protein is linked to extracellular vesicles without any presence of viral RNA in these vesicles. In conclusion, our findings suggest that Spike protein and/or viral RNA fragments persist in the recovered COVID-19 patients with PASC, regardless of their presence or absence during the acute COVID-19 phase. These results may help in understanding the reason(s) for why patients experience PASC symptoms and may offer potential therapeutic targets.
Characterizations of enhanced infectivity and antibody evasion of Omicron BA.2.75
Recently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a local growth advantage over BA.2.38, BA.2.76 and BA.5 in India. The underlying mechanism of BA.2.75’s enhanced infectivity, especially compared to BA.5, remains unclear. Here, we show that BA.2.75 exhibits substantially higher ACE2-binding affinity than BA.5. Also, BA.2.75 spike shows decreased thermostability and increased “up” RBD conformation in acidic conditions, suggesting enhanced low-pH-endosomal cell-entry pathway utilization. BA.2.75 is less humoral immune evasive than BA.4/BA.5 in BA.1/BA.2 breakthrough-infection convalescents; however, BA.2.75 shows heavier neutralization evasion in Delta breakthrough-infection convalescents. Importantly, plasma from BA.5 breakthrough infection exhibit significantly weaker neutralization against BA.2.75 than BA.5, mainly due to BA.2.75’s distinct RBD and NTD-targeting antibody escaping pattern from BA.4/BA.5. Additionally, Evusheld and Bebtelovimab remain effective against BA.2.75, and Sotrovimab recovered RBD-binding affinity. Together, our results suggest BA.2.75 may prevail after the global BA.4/BA.5 wave, and its increased receptor-binding capability could allow further incorporation of immune-evasive mutations.
Further humoral immunity evasion of emerging SARS-CoV-2 BA.4 and BA.5 subvariants
Multiple BA.4 and BA.5 subvariants with R346 mutations on the spike glycoprotein have been identified in various countries, such as BA.4.6/BF.7 harboring R346T, BA.4.7 harboring R346S, and BA.5.9 harboring R346I. These subvariants, especially BA.4.6, exhibit substantial growth advantages compared to BA.4/BA.5. In this study, we showed that BA.4.6, BA.4.7, and BA.5.9 displayed higher humoral immunity evasion capability than BA.4/BA.5, causing 1.5 to 1.9-fold decrease in NT50 of the plasma from BA.1 and BA.2 breakthrough-infection convalescents compared to BA.4/BA.5. Importantly, plasma from BA.5 breakthrough-infection convalescents also exhibits significant neutralization activity decrease against BA.4.6, BA.4.7, and BA.5.9 than BA.4/BA.5, showing on average 2.4 to 2.6-fold decrease in NT50. For neutralizing antibody drugs, Bebtelovimab remains potent, while Evusheld is completely escaped by these subvariants. Together, our results rationalize the prevailing advantages of the R346 mutated BA.4/BA.5 subvariants and urge the close monitoring of these mutants, which could lead to the next wave of the pandemic.
Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques
To prepare for future coronavirus (CoV) pandemics, it is desirable to generate vaccines capable of eliciting broadly neutralizing antibody responses to CoVs. Here, we show that immunization of macaques with SARS-CoV-2 spike (S) protein with a two-shot protocol generated potent serum receptor binding domain cross-neutralizing antibody responses to both SARS-CoV-2 and SARS-CoV-1. Furthermore, responses were equally effective against most SARS-CoV-2 variants of concern (VOCs) and some were highly effective against Omicron. This result contrasts with human infection or many two-shot vaccination protocols where responses were typically more SARS-CoV-2 specific and where VOCs were less well neutralized. Structural studies showed that cloned macaque neutralizing antibodies, particularly using a given heavy chain germline gene, recognized a relatively conserved region proximal to the angiotensin converting enzyme 2 receptor binding site (RBS), whereas many frequently elicited human neutralizing antibodies targeted more variable epitopes overlapping the RBS. B cell repertoire differences between humans and macaques appeared to influence the vaccine response. The macaque neutralizing antibodies identified a pan-SARS–related virus epitope region less well targeted by human antibodies that could be exploited in rational vaccine design.
Distinguishing features of Long COVID identified through immune profiling
SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID1–3. Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions1–3; however, the basic biological mechanisms responsible for these debilitating symptoms are unclear. Here, 215 individuals were included in an exploratory, cross-sectional study to perform multi-dimensional immune phenotyping in conjunction with machine learning methods to identify key immunological features distinguishing Long COVID. Marked differences were noted in specific circulating myeloid and lymphocyte populations relative to matched control groups, as well as evidence of elevated humoral responses directed against SARS-CoV-2 among participants with Long COVID. Further, unexpected increases were observed in antibody responses directed against non-SARS-CoV-2 viral pathogens, particularly Epstein-Barr virus. Analysis of circulating immune mediators and various hormones also revealed pronounced differences, with levels of cortisol being uniformly lower among participants with Long COVID relative to matched control groups. Integration of immune phenotyping data into unbiased machine learning models identified significant distinguishing features critical in accurate classification of Long COVID, with decreased levels of cortisol being the most significant individual predictor. These findings will help guide additional studies into the pathobiology of Long COVID and may aid in the future development of objective biomarkers for Long COVID.
Will ‘Centaurus’ be the next global coronavirus variant? Indian cases offers clues
The BA.2.75 variant is rising fast in the country, but hospitalization rates are low so far.
August 9, 2022
SARS-CoV-2 hybrid immunity: silver bullet or silver lining?
The COVID-19 pandemic is far from over. SARS-CoV-2 mutates relatively slowly (~1 × 10−6 per base per infection cycle); yet, the world continues to experience a series of viral surges fuelled by the evolving sub-lineages of the Omicron variant. Now, 32 months into the pandemic, more than 66% of the world’s population is estimated to have some form of immunity against SARS-CoV-2, either through infection (‘natural’), vaccination (‘artificial’) or both (‘hybrid’). Hybrid immunity emerged as a form of ‘super immunity’ in 2021, when convalescent people receiving vaccine doses were found to have neutralizing antibody titres on average 50-fold higher than unvaccinated convalescent individuals1. As breakthrough infections emerged in vaccinated people, hybrid immunity became an established arm of the anti-SARS-CoV-2 immune landscape. What do we now know about hybrid immunity and its ‘super immunity’ abilities?
While making virus-specific immune responses to SARS-CoV-2, residual B and T cell diversity are key to making responses to concurrent co-infections and/or cancers. We applied an antigen receptor–sequencing technology and provide a comprehensive description of the global immune repertoire in hospitalized and nonhospitalized individuals infected with SARS-CoV-2. Although B cell diversity predictably narrowed, significant narrowing of αβ and γδ T cell diversity was unexpectedly observed only in those aged over 50, which is a major inflexion point for COVID-19–associated mortality. Such a discrepancy in how older persons mount T cell responses to a new virus may be considered a risk factor for the elderly, particularly vis-à-vis new virus variants against which T cell immunity may be particularly important.
CORONAVIRUS CD8 T Cells Contribute to Va ccine Protection Against SARS-CoV-2 in Macaques
Spike-specific neutralizing antibodies (NAbs) are generally considered key correlates of vaccine protection against SARS-CoV-2 infection. Recently, robust vaccine prevention of severe disease with SARS-CoV-2 variants that largely escape NAb responses has been reported, suggesting a role for other immune parameters for viro-logic control. However, direct data demonstrating a role of CD8+ T cells in vaccine protection has not yet been reported. In this study, we show that vaccine-elicited CD8+ T cells contribute substantially to virologic control following SARS-CoV-2 challenge in rhesus macaques. We vaccinated 30 macaques with a single immunization of the adenovirus vector-based vaccine Ad26.COV2.S or sham and then challenged them with 5x105 TCID50 SARS- CoV-2 B.1.617.2 (Delta) by the intranasal and intratracheal routes. All vaccinated animals were infected by this high-dose challenge but sho wed rapid virologic control in nasal sw abs and br onchoalveolar lavage by day 4 following challenge. However, administration of an anti-CD8α or anti-CD8β depleting monoclonal antibody in vaccinated animals prior to SARS-CoV-2 challenge resulted in higher levels of peak and day 4 virus in both the upper and lower respiratory tracts. These data demonstrate that CD8+ T cells contribute substantially to vaccine protection against SARS-CoV-2 replication in macaques.
Covid-19: What we know about the BA.4 and BA.5 omicron variants
Two omicron subvariants have come to dominate infections worldwide. Elisabeth Mahase summarises what we know about them so far
Long-COVID treatments: why the world is still waiting
In the absence of a solid evidence base, some physicians worry about potential harm from long-COVID treatments. Shinichiro Morioka, deputy director of the Disease Control and Prevention Center at the National Center for Global Health and Medicine in Tokyo, says that some doctors are using epipharyngeal abrasive therapy, in which the throat is scraped with cotton swabs soaked in zinc chloride. The aim is to decrease inflammation at a key site of coronavirus infection, he says. Some physicians say they have achieved promising results in small trials with no control group5. “But I do not think this is evidence-based, and it is invasive for patients,” says Morioka. “We need to run randomized controlled trials.” At the moment, he does not know of any randomized controlled trials for this or any other long-COVID treatment in Japan.
August 8, 2022
Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors
First-generation vaccines and drugs have helped reduce disease severity and blunt the spread of SARS-CoV-2. However, ongoing virus transmission and evolution and increasing selective pressures have the potential to yield viral variants capable of resisting these interventions. Here, we investigate the susceptibility of natural variants of the main protease (Mpro/3CLpro) of SARS-CoV-2 to protease inhibitors. Multiple single amino acid changes in Mpro confer resistance to nirmatrelvir (the active component of Paxlovid). An additional inhibitor in clinical development, ensitrelvir, shows a different resistance mutation profile. Importantly, phylogenetic analyses indicate that nirmatrelvir-resisting variants have pre-existed the introduction of this drug into the human population and are capable of spreading. A similarly strong argument can be made for ensitrelvir. These results caution against broad administration of protease inhibitors as stand-alone therapies and encourage the development of additional protease inhibitors and other antiviral drugs with different mechanisms of action and resistance profiles.
Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir
Nirmatrelvir, an oral antiviral targeting the 3CL protease of SARS-CoV-2, has been demonstrated to be clinically useful in reducing hospitalization or death due to COVID-191,2. However, as SARS-CoV-2 has evolved to become resistant to other therapeutic modalities3–9, there is a concern that the same could occur for nirmatrelvir. Here, we have examined this possibility by in vitro passaging of SARS-CoV-2 in increasing concentrations of nirmatrelvir using two independent approaches, including one on a large scale in 480 wells. Indeed, highly resistant viruses emerged from both, and their sequences revealed a multitude of 3CL protease mutations. In the experiment done at scale, 53 independent viral lineages were selected with mutations observed at 23 different residues of the enzyme. Yet, several common mutational pathways to nirmatrelvir resistance were preferred, with a majority of the viruses descending from T21I, P252L, or T304I as precursor mutations. Construction and analysis of 13 recombinant SARS-CoV-2 clones, each containing a unique mutation or a combination of mutations showed that the above precursor mutations only mediated low-level resistance, whereas greater resistance required accumulation of additional mutations. E166V mutation conferred the strongest resistance (∼300-fold), but this mutation resulted in a loss of viral replicative fitness that was restored by compensatory changes such as L50F and T21I. Structural explanations are discussed for some of the mutations that are proximal to the drug-binding site, as well as cross-resistance or lack thereof to ensitrelvir, another clinically important 3CL protease inhibitor. Our findings indicate that SARS-CoV-2 resistance to nirmatrelvir does readily arise via multiple pathways in vitro, and the specific mutations observed herein form a strong foundation from which to study the mechanism of resistance in detail and to shed light on the design of next generation protease inhibitors.
Virological characteristics of the SARS-CoV-2 Omicron BA.2.75
SARS-CoV-2 Omicron BA.2.75 emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically different from BA.5, the currently predominant BA.2 descendant. Here, we showed that the effective reproduction number of BA.2.75 is greater than that of BA.5. While the sensitivity of BA.2.75 to vaccination- and BA.1/2 breakthrough infection-induced humoral immunity was comparable to that of BA.2, the immunogenicity of BA.2.75 was different from that of BA.2 and BA.5. Three clinically-available antiviral drugs were effective against BA.2.75. BA.2.75 spike exhibited a profound higher affinity to human ACE2 than BA.2 and BA.5 spikes. The fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were comparable to those of BA.5 but were greater than those of BA.2. Our multiscale investigations suggest that BA.2.75 acquired virological properties independently of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5.
August 5, 2022
Compared with patients aged 0–17 years without previous COVID-19, those with previous COVID-19 had higher rates of acute pulmonary embolism (adjusted hazard ratio = 2.01), myocarditis and cardiomyopathy (1.99), venous thromboembolic event (1.87), acute and unspecified renal failure (1.32), and type 1 diabetes (1.23), all of which were rare or uncommon in this study population. COVID-19 prevention strategies, including vaccination for all eligible persons aged ≥6 months, are critical to preventing SARS-CoV-2 infection and subsequent illness, and reducing the public health impact of post-COVID symptoms and conditions among persons aged 0–17 years.
On July 19, 2022, the Advisory Committee on Immunization Practices made an interim recommendation for use of the Novavax vaccine in persons aged ≥18 years as a primary 2-dose series vaccination for the prevention of COVID-19. The adjuvanted, protein subunit–based Novavax COVID-19 vaccine provides an additional option for unvaccinated adults, increasing flexibility for the public and for vaccine providers. Vaccination is important for protection against COVID-19.
During the first 2 years of the U.S. COVID-19 pandemic, pediatric centers anecdotally reported increased rates of intracranial bacterial infections, many of which were diagnosed during or immediately after an infection with SARS-CoV-2, the virus that causes COVID-19 (1,2). Although intracranial bacterial infections occur as a rare complication of partially treated or untreated bacterial rhinosinusitis in adolescents as well as mastoiditis in children of all ages (3), a 236% increase in cases among children was observed at a Michigan children’s hospital (Aldrich A and Ogrin S, Helen DeVos Children’s Hospital of Spectrum Health, unpublished data, 2022). Most of these cases were in infants and children aged <12 years and associated with a diversity of identified pathogens, including a range of Streptococcus species with more severe disease requiring extended intensive care unit admission and multiple surgical interventions; many of the cases had recent or concurrent SARS-CoV-2 infection.
Understanding COVID-19-associated coagulopathy
COVID-19-associated coagulopathy (CAC) is a life-threatening complication of SARS-CoV-2 infection. However, the underlying cellular and molecular mechanisms driving this condition are unclear. Evidence supports the concept that CAC involves complex interactions between the innate immune response, the coagulation and fibrinolytic pathways, and the vascular endothelium, resulting in a procoagulant condition. Understanding of the pathogenesis of this condition at the genomic, molecular and cellular levels is needed in order to mitigate thrombosis formation in at-risk patients. In this Perspective, we categorize our current understanding of CAC into three main pathological mechanisms: first, vascular endothelial cell dysfunction; second, a hyper-inflammatory immune response; and last, hypercoagulability. Furthermore, we pose key questions and identify research gaps that need to be addressed to better understand CAC, facilitate improved diagnostics and aid in therapeutic development. Finally, we consider the suitability of different animal models to study CAC.
In this cohort study of 140 000 class meetings at a large US university, there were over 850 cases of SARS-CoV-2 infection identified through weekly surveillance testing of all students and faculty on campus during the fall 2021 semester. There were 9 instances of potential in-class transmission identified as identical lineages confirmed by SARS-CoV-2 genome sequencing, and none of these instances were confirmed to be in-class transmission.
Screening of more than 50 000 youths in diverse populations of Colorado and Bavaria found no association of SARS-CoV-2 infection with autoimmunity related to development of type 1 diabetes. Study limitations include the low prevalence of autoantibodies, limiting the power to detect an increase in risk associated with SARS-CoV-2 infection. Moreover, the cross-sectional design did not allow determination of whether autoantibodies developed before or after SARS-CoV-2 infection. Long-term follow-up of persons with preexisting autoimmunity is necessary to determine whether SARS-CoV-2 accelerates progression to clinical diabetes.
Just the Plague: Reflections on State Control of Infectious Outbreaks
n 1939 prominent Soviet microbiologist Abram Lvovich Berlin was working on a plague vaccine as deputy director of the Workers’ and Peasants’ Red Army Biotechnology Institute, then located in Vlasikha, on the outskirts of Moscow. He immunized laboratory animals with a candidate live-attenuated plague vaccine and challenged them with Yersinia pestis (then called Pasteurella pestis) aerosol, and he was infected in the process. He was called to Moscow to present interim results of his vaccine development efforts to superiors; shared a train compartment with numerous fellow travelers; came into close contact with National Hotel receptionists, its barber, and other visitors and residents; then was evaluated by a physician for emerging cough and malaise before presenting his research results to high-ranking officials.
August 4, 2022
Antibody escape and cryptic cross-domain stabilization in the SARS-CoV-2 Omicron spike protein
The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the repeated emergence of variants of concern. For the Omicron variant, sub-lineages BA.1 and BA.2 respectively contain 33 and 29 nonsynonymous and indel spike protein mutations. These amino acid substitutions and indels are implicated in increased transmissibility and enhanced immune evasion. By reverting individual Spike mutations of BA.1 or BA.2, we characterize the molecular effects of the Omicron spike mutations on expression, ACE2 receptor affinity, and neutralizing antibody recognition. We identified key mutations enabling escape from neutralizing antibodies at a variety of epitopes. Stabilizing mutations in the N-terminal and S2 domains of the spike protein can compensate for destabilizing mutations in the receptor binding domain, enabling the record number of mutations in Omicron. Our results provide a comprehensive account of the mutational effects in the Omicron spike protein and illuminate previously uncharacterized mechanisms of host evasion.
In this cohort study, 88.2% of patients reporting a COVID-19–related smell or taste dysfunction completely recovered within 2 years. A late recovery was observed in 10.9% of patients. Although these results must be interpreted with caution owing to study limitations (eg, data were self-reported based on a cross-sectional survey; outcomes not specifically validated for olfactory loss were used; a psychophysical evaluation of the chemosensory function was not performed; the sample was relatively small and geographically limited, with patients with more severe symptoms not included; data regarding potential treatments used for chemosensory impairment were lacking), contrary to what is often reported, patients should be reassured that recovery from smell or taste impairment may continue for many months after the onset. These results apply to patients infected in the pre-Omicron period. COVID-19 driven by the SARS-CoV-2 Omicron variant has been indeed observed to less frequently and less severely affect chemosensory function.
August 3, 2022
Animal Reservoirs—Where the Next SARS-CoV-2 Variant Could Arise
In April 2020, when hundreds of thousands of people worldwide had already succumbed to COVID-19, one infected individual—4-year-old Nadia—made global headlines. A Malayan tiger residing in New York’s Bronx Zoo, Nadia was among the first animals known to have contracted the virus from a human, likely a caretaker.
Addressing the Long-term Effects of COVID-19
The COVID-19 pandemic is the most significant medical and public health challenge the US has encountered in the last 100 years. As of July 26, 2022, an estimated 90 million cases of COVID-19 have been reported in the US, with an estimated 1 million COVID-19–related deaths. The current number of SARS-CoV-2 infections is difficult to estimate accurately, considering that many individuals with positive self-test results do not seek care or report their infection. At the same time, new coronavirus variants continue to emerge, with Omicron subvariants such as BA.5 and BA.4 now identified as the dominant circulating strains.
In this cross-sectional study of 2031 US adults with children aged 6 months through 4 years, half indicated they intended to get their child a COVID-19 vaccine at some point, but only one-fifth intended to do so within 3 months of the child’s eligibility. The top concerns about and facilitators to COVID-19 vaccination for this age group related to COVID-19 vaccination safety and efficacy.
In this cohort study of individuals newly diagnosed with COVID-19, 75% continued to have positive RAT results, while 35% had culturable virus on day 6. Everyone with a negative day-6 RAT result had a negative viral culture. However, only 50% of those with a positive RAT result had culturable virus. Acknowledging the caveats of a small cohort of mostly young, vaccinated, nonhospitalized individuals with a presumed Omicron variant and potential variation in self-sampling techniques and lab-based culture methods, these data suggest that a negative RAT result in individuals with residual symptoms could provide reassurance about ending isolation. However, a universal requirement of a negative RAT result may unduly extend isolation for those who are no longer infectious. Meanwhile, a recommendation to end isolation based solely on the presence of improving symptoms risks releasing culture-positive, potentially infectious individuals prematurely, underscoring the importance of proper mask wearing and avoidance of high-risk transmission venues through day 10.
Rate of SARS-CoV-2 Reinfection During an Omicron Wave in Iceland
In this population-based cohort study, a substantial proportion of persons experienced SARS-CoV-2 reinfection during the first 74 days of the Omicron wave in Iceland, with rates as high 15.1% among those aged 18 to 29 years. Longer time from initial infection was associated with a higher probability of reinfection, although the difference was smaller than expected. Surprisingly, 2 or more doses of vaccine were associated with a slightly higher probability of reinfection compared with 1 dose or less. This finding should be interpreted with caution because of limitations of our study, which include the inability to adjust for the complex relationships among prior infection, vaccine eligibility, and underlying conditions. Importantly, by December 1, 2021, all persons aged 12 years and older were eligible for 2 or more vaccine doses free of charge, and 71.1% of the Icelandic population had been vaccinated,5 compared with only 25.5% of our cohort of previously infected persons. Our results suggest that reinfection is more common than previously thought. Now the key question is whether infection with the Omicron variant will produce better protection against Omicron reinfection, compared with other variants.
The findings of this case-control study suggest that 2 doses of BNT162b2 were associated with preventing ED and UC encounters for ARI caused by either the Delta or Omicron variants of SARS-CoV-2 in the first few months after vaccination. However, this effectiveness waned over time, although waning was more pronounced for the Omicron variant. A third dose of BNT162b2 was associated with improved protection beyond that seen initially after 2 doses. These findings underscore the important role of booster doses to enhance protection against COVID-19 for adolescents aged 12 to 17 years.
A first update on mapping the human genetic architecture of COVID-19
The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity.
August 2, 2022
Maternal Death Rate Increased During Early COVID-19 Pandemic
The investigators analyzed National Center for Health Statistics data from people who died within 42 days after pregnancy. In 2018, 2019, and the first quarter of 2020, the maternal death rate was 18.8 per 100 000 live births. During April to December 2022, the rate increased to 25.1 per 100 000 live births, a relative increase of 33.3%. The maternal death rate increased 74.2% among Hispanic individuals, 40.2% among non-Hispanic Black individuals, and 17.2% among non-Hispanic White individuals during the study period.
Sickle Cell Trait Associated With Kidney Failure and COVID-19 Death
Sickle cell trait (SCT) should be considered an adverse prognostic factor for COVID-19, a genetic association study suggests.
In this cohort study including 10 920 patients, the use of neoadjuvant-intent chemotherapy and hormonal treatment increased during the COVID-19 era, but there was substantial regional variability. Bridging hormonal therapy was a more common adaptation to cancer treatment in the COVID-19 era than neoadjuvant chemotherapy; neoadjuvant-intent systemic treatment was not associated with short-term outcomes in the COVID-19 era.
National Estimates of Increase in US Mechanical Ventilator Supply During the COVID-19 Pandemic
This cross-sectional study found a substantial increase in adult and pediatric mechanical ventilators reported by acute care hospitals in 2020 compared with 2019. Study limitations include possible response bias. The AHA Annual Survey did not differentiate between ventilator functionality, changes in numbers of anesthesia ventilators, or transport, backup, or rental ventilators, nor did it account for temporary ventilator allocation coordinated through state public health departments or the Dynamic Ventilator Reserve.5 The increase in ventilators that were deployed in hospitals was not correlated with the state’s COVID-19 ICU burden, but this finding may not account for more dynamic shifts in ventilator stock across hospitals during waves of the pandemic. For both the current COVID-19 pandemic as well as future pandemic preparedness, these findings may help guide policy makers in deploying ventilators to states with the most urgent need of ventilators.
In the spring of 2020, US regions impacted early by COVID-19, such as northern New Jersey and New York City, exceeded the usual mechanical ventilation capability at numerous hospitals. As COVID-19 spread to other communities with limited immunity, similar challenges to provide surge mechanical ventilation were reported. Hospitals, health care systems, and jurisdictional authorities sought to purchase more mechanical ventilators and quickly realized that the supply chain could not accommodate the perceived need. Numerous creative engineering ideas were proposed to augment the supply of resuscitators or mechanical ventilators. Tremendous public and governmental effort focused on preventing shortages of these potentially life-saving devices and on strategies to ration them should demand exceed supply.
Viral and Symptom Rebound in Untreated COVID-19 Infection
Findings: In both the primary and secondary analyses, 12% of participants had viral rebound. Viral rebounders were older than non-rebounders (median 54 vs 47 years, P=0.04). Symptom rebound occurred in 27% of participants after initial symptom improvement and in 10% of participants after initial symptom resolution. The combination of high-level viral rebound to ≥5.0 log10 RNA copies/mL and symptom rebound after initial improvement was observed in 1-2% of participants. Interpretation: Viral RNA rebound or symptom relapse in the absence of antiviral treatment is common, but the combination of high-level viral and symptom rebound is rare.
In this multicenter cohort study of 29 611 health care workers in Israel, the breakthrough infection rate among those who received 4 doses was 6.9% compared with 19.8% in those who received 3 doses. These findings suggest that a fourth vaccine dose was effective in preventing breakthrough COVID-19 infections in health care workers, helping to maintain the function of the health care system during the pandemic.
Heart disease after COVID: what the data say
Some studies suggest that the risk of cardiovascular problems, such as a heart attack or stroke, remains high even many months after a SARS-CoV-2 infection clears up. Researchers are starting to pin down the frequency of these issues and what is causing the damage.
Omicron BA.2 breakthrough infection enhances cross-neutralization of BA.2.12.1 and BA.4/BA.5
Recently, we reported that BNT162b2-vaccinated individuals after Omicron BA.1 breakthrough infection have strong serum neutralizing activity against Omicron BA.1, BA.2, and previous SARS-CoV-2 variants of concern (VOCs), yet less against the highly contagious Omicron sublineages BA.4 and BA.5 that have displaced previous variants. As the latter sublineages are derived from Omicron BA.2, we characterized serum neutralizing activity of COVID-19 mRNA vaccine triple-immunized individuals who experienced BA.2 breakthrough infection. We demonstrate that sera of these individuals have broadly neutralizing activity against previous VOCs as well as all tested Omicron sublineages, including BA.2 derived variants BA.2.12.1, BA.4/BA.5. Furthermore, applying antibody depletion we showed that neutralization of BA.2 and BA.4/BA.5 sublineages by BA.2 convalescent sera is driven to a significant extent by antibodies targeting the N-terminal domain (NTD) of the spike glycoprotein, whereas their neutralization by Omicron BA.1 convalescent sera depends exclusively on antibodies targeting the receptor binding domain (RBD). These findings suggest that exposure to Omicron BA.2, in contrast to BA.1 spike glycoprotein, triggers significant NTD specific recall responses in vaccinated individuals and thereby enhances the neutralization of BA.4/BA.5 sublineages. Given the current epidemiology with a predominance of BA.2 derived sublineages like BA.4/BA.5 and rapidly ongoing evolution, these findings are of high relevance for the development of Omicron adapted vaccines.
August 1, 2022
Antigenic characterization of the SARS-CoV-2 Omicron subvariant BA.2.75
The SARS-CoV-2 Omicron subvariant BA.2.75 emerged recently and appears to be spreading rapidly. It has nine mutations in its spike compared to BA.2, raising concerns it may further evade vaccine-elicited and therapeutic antibodies. Here, we found BA.2.75 to be moderately more neutralization resistant to sera from vaccinated/boosted individuals than BA.2 (1.8-fold), similar to BA.2.12.1 (1.1-fold), but more neutralization sensitive than BA.4/5 (0.6-fold). Relative to BA.2, BA.2.75 showed heightened resistance to class 1 and class 3 monoclonal antibodies to the receptor-binding domain, while gaining sensitivity to class 2 antibodies. The resistance was largely conferred by the G446S and R460K mutations. Of note, BA.2.75 was slightly resistant (3.7-fold) to bebtelovimab, the only therapeutic antibody with potent activity against all Omicron subvariants. BA.2.75 also exhibited higher receptor binding affinity than other Omicron subvariants. BA.2.75 provides yet another example of the ongoing evolution of SARS-CoV-2 as it gains transmissibility while incrementally evading antibody neutralization.
Coenzyme Q10 as Treatment of Post COVID-19 Condition
Findings: From May 25th, 2021, to September 22nd, 2021, 121 participants underwent randomization, and 119 completed both dosing periods – 59 and 60 in group A and B, respectively. At baseline, the mean PCC-related symptom score was 43·06 (95% CI: 40·18;45·94), and the mean EQ-5D health index was 0·66 (95% CI: 0·64;0·68). The difference between CoQ10 and placebo was not significant with respect to either the change in EQ-5D health index (with a mean difference of 0·01; 95% CI: -0·02;0·04; p =0·45) or the change in PCC-related symptom score (with a mean difference of -1·18; 95% CI: -3·54;1·17; p =0·32). Interpretation: We conclude that CoQ10 treatment does not appear to significantly reduce the number or severity of PCC-related symptoms when compared to placebo.
In children aged 5-11 years, two doses of BNT162b2 provide moderate protection against symptomatic Omicron infection and high protection against severe outcomes. Protection wanes more rapidly for infection than severe outcomes. Longer dosing intervals may confer higher protection against symptomatic infection in the short-term, but further evaluation of the duration of the observed protection is needed.
Evolution of SARS-CoV-2 Shedding in Exhaled Breath Aerosols
Aerosol inhalation is increasingly well recognized as a major if not primary mode of transmission of SARS-CoV-21,2. Over the course of the COVID-19 pandemic, three highly transmissible lineages evolved and became globally dominant3. One hypothesis to explain increased transmissibility is that natural selection favours variants with higher rates of viral aerosol shedding. However, the extent of aerosol shedding of successive SARS-CoV-2 variants is unknown. Here, we demonstrate that viral shedding (measured as RNA copies) into exhaled breath aerosol was significantly greater during infections with Alpha, Delta, and Omicron than with ancestral strains and variants not associated with increased transmissibility. The three highly transmissible variants independently evolved a high viral aerosol shedding phenotype, demonstrating convergent evolution. We did not observe statistically significant differences in rates of shedding between Alpha, Delta, and Omicron infections. The highest shedder in our study, however, had an Omicron infection and shed three orders of magnitude more viral RNA copies than the maximum observed for Delta and Alpha4. Our results also show that fully vaccinated and boosted individuals, when infected, can shed infectious SARS-CoV-2 via exhaled breath aerosols. These findings provide additional evidence that inhalation of infectious aerosols is the dominant mode of transmission and emphasize the importance of ventilation, filtration, and air disinfection to mitigate the pandemic and protect vulnerable populations. We anticipate that monitoring aerosol shedding from new SARS-CoV-2 variants and emerging pathogens will be an important component of future threat assessments and will help guide interventions to prevent transmission via inhalation exposure.
July 31, 2022
The Efficacy of Facemasks in the Prevention of COVID-19: A Systematic Review
Facemasks have become a symbol of disease prevention in the context of COVID-19; yet, there still exists a paucity of collected scientific evidence surrounding their epidemiological efficacy in the prevention of SARS-CoV-2 transmission. This systematic review sought to analyze the efficacy of facemasks, regardless of type, on the prevention of SARS-CoV-2 transmission in both healthcare and community settings. The initial review yielded 1732 studies, which were reviewed by three study team members. Sixty-one full text studies were found to meet entry criteria, and 13 studies yielded data that was used in the final analysis. In all, 243 subjects were infected with COVID-19, of whom 97 had been wearing masks and 146 had not. The probability of getting COVID-19 for mask wearers was 7% (97/1463, p=0.002), for non-mask wearers, probability was 52% (158/303, p=0.94). The Relative Risk of getting COVID-19 for mask wearers was 0.13 (95% CI: 0.10-0.16). Based on these results, we determined that across healthcare and community settings, those who wore masks were less likely to contact COVID-19. Future investigations are warranted as more information becomes available.
July 30, 2022
Booster vaccination with mRNA-1273 COVID-19 vaccine was more effective than BNT162b2 in preventing SARS-CoV-2 infection and COVID-19 hospitalisation during the first 12 weeks after vaccination, during a period of Delta followed by Omicron variant dominance.
July 29, 2022
Among persons aged ≥50 years who reported homologous mRNA COVID-19 vaccination, injection site and systemic reactions were less frequent after a second booster dose than after the first booster dose. Ninety-five percent of 8,515 events reported to the Vaccine Adverse Event Reporting System were nonserious.
July 27, 2022
The primary outcomes were the proportions of patients remaining with smell or taste dysfunction. Secondary outcomes were the odds ratios of prognostic variables associated with recovery of smell and taste. A substantial proportion of patients with covid-19 might develop long lasting change in their sense of smell or taste. This could contribute to the growing burden of long covid.
Risk of severe COVID-19 infection among adults with prior exposure to children
Epidemiologic data consistently show strong protection for young children against severe COVID-19 illness. Several mechanisms have been proposed to explain this phenomenon, including cross-reactive immunity—in which prior exposure to non-SARS-CoV-2 coronaviruses that commonly infect children confers some resistance to severe COVID-19 illness. We identified 3,126,427 adults (24% [N = 743,814] with children ≤18, and 8.8% [N = 274,316] with youngest child 0–5 years) to assess whether parents of young children—who have high exposure to non-SARS-CoV-2 coronaviruses—may also benefit from potential cross-immunity. In a large, real-world population, exposure to young children was strongly associated with less severe COVID-19 illness, after balancing known COVID-19 risk factors. This epidemiologic signal suggests endemic coronavirus cross-immunity may play a role in protection against severe COVID-19 outcomes.
SARS-CoV-2 S2–targeted vaccination elicits broadly neutralizing antibodies
Because variants of SARS-CoV-2 continue to arise and reduce the protection afforded by vaccination or prior infection, it is becoming increasingly important that vaccines be developed that target more conserved regions of the SARS-CoV-2 spike protein. Here, Ng et al. tested whether antibodies targeting the more conserved S2 subunit of the spike protein could confer protection against infection with distinct coronaviruses. The authors observed that S2-targeted vaccination produced antibodies in mice that could neutralize diverse alphacoronaviruses and betacoronaviruses. These antibodies had increased breadth relative to antibodies elicited by full-length spike protein vaccination, suggesting less repertoire focusing. Thus, S2-targeted vaccination may be a strategy to achieve pan-SARS-CoV-2 immunity.
Effectiveness Associated With Vaccination After COVID-19 Recovery in Preventing Reinfection
In this cohort study of more than 95 000 Rhode Island residents from March 2020 to December 2021, including residents and employees of long-term congregate care (LTCC) facilities, completion of the primary vaccination series after recovery from COVID-19 was associated with 49% protection from reinfection among LTCC residents, 47% protection among LTCC employees, and 62% protection in the general population during periods when wild type, Alpha, and Delta strains of SARS-CoV-2 were predominant. These findings suggest that among people who have recovered from COVID-19, subsequent completion of the primary vaccination series reduced the risk of reinfection by approximately half.
July 26, 2022
How long is COVID infectious? What scientists know so far
When the US Centers for Disease Control and Prevention (CDC) halved its recommended isolation time for people with COVID-19 to five days back in December, it said that the change was motivated by science. Specifically, the CDC said that most SARS-CoV-2 transmission occurs early in the course of the illness, in the one to two days before the onset of symptoms and for two to three days after. Many scientists disputed that decision then and they continue to do so. Such dissent is bolstered by a series of studies confirming that many people with COVID-19 remain infectious well into the second week after they first experience symptoms. Reductions in the length of the recommended isolation period — now common around the world — are driven by politics, they say, rather than any reassuring new data.
This is the eighth update alert for a living rapid review (1) on the use of masks for the prevention of respiratory virus infections, including SARS-CoV-2, in health care and community settings. The first 3 updates (2–4) were monthly, after which the interval was switched to bimonthly (5, 6). Beginning in June 2021, the interval was extended to biannually. For this update, searches were done from 3 December 2021 to 2 June 2022 using the same search methods as the original review. Inclusion was restricted to randomized trials and observational studies that controlled for confounders. Non–peer-reviewed studies were excluded unless they were based on data collected after February 2021 to capture evidence on mask use in the B.1.617.2 (Delta) and B.1.1.529 (Omicron) variant predominant periods. The update searches identified 1592 citations. No new randomized controlled trials (RCTs) and 5 new observational studies on the association of mask use and SARS-CoV-2 infection met inclusion criteria (Supplement Table 1). Three studies were done in community settings (7–9), and 2 studies (10, 11) were done in health care settings. One preprint study (9) of mask use in community settings collected data during Delta and Omicron predominant periods; the other studies were done before the emergence of these variants. All studies had methodological limitations, including unclear or low participation rate, potential recall bias, and failure to report attrition or missing data (Supplement Table 2).
SARS-CoV-2 mRNA vaccination elicits robust antibody responses in children
Although children have been largely spared from coronavirus disease 2019 (COVID-19), the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) with increased transmissibility, combined with fluctuating mask mandates and school re-openings, have led to increased infections and disease among children. Thus, there is an urgent need to roll out COVID-19 vaccines to children of all ages. However, whether children respond equivalently to adults to mRNA vaccines and whether dosing will elicit optimal immunity remains unclear. Here we aimed to deeply profile the vaccine-induced humoral immune response in 6 to 11 year old children receiving either a pediatric (50 μg) or adult (100 μg) dose of the mRNA-1273 vaccine and to compare these responses to vaccinated adults, infected children, and children that experienced multisystem inflammatory syndrome in children (MIS-C). Children elicited an IgG-dominant vaccine-induced immune response, surpassing adults at a matched 100 μg dose, but more variable immunity at a 50 μg dose. Irrespective of titer, children generated antibodies with enhanced Fc-receptor binding capacity. Moreover, like adults, children generated cross-VOC humoral immunity, marked by a decline of omicron-specific receptor binding domain-binding, but robustly preserved omicron spike protein-binding. Fc-receptor binding capabilities were also preserved in a dose dependent manner. These data indicate that both the 50 μg and 100 μg doses of mRNA vaccination in children elicits robust cross-VOC antibody responses and that 100 μg doses in children results in highly preserved omicron-specific functional humoral immunity.
The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic
Understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 is critical to preventing zoonotic outbreaks before they become the next pandemic. The Huanan Seafood Wholesale Market in Wuhan, China, was identified as a likely source of cases in early reports but later this conclusion became controversial. We show the earliest known COVID-19 cases from December 2019, including those without reported direct links, were geographically centered on this market. We report that live SARS-CoV-2 susceptible mammals were sold at the market in late 2019 and, within the market, SARS-CoV-2-positive environmental samples were spatially associated with vendors selling live mammals. While there is insufficient evidence to define upstream events, and exact circumstances remain obscure, our analyses indicate that the emergence of SARS-CoV-2 occurred via the live wildlife trade in China, and show that the Huanan market was the epicenter of the COVID-19 pandemic.
The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2
Understanding the circumstances that lead to pandemics is important for their prevention. Here, we analyze the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic. We show that SARS-CoV-2 genomic diversity before February 2020 likely comprised only two distinct viral lineages, denoted A and B. Phylodynamic rooting methods, coupled with epidemic simulations, reveal that these lineages were the result of at least two separate cross-species transmission events into humans. The first zoonotic transmission likely involved lineage B viruses around 18 November 2019 (23 October–8 December), while the separate introduction of lineage A likely occurred within weeks of this event. These findings indicate that it is unlikely that SARS-CoV-2 circulated widely in humans prior to November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. As with other coronaviruses, SARS-CoV-2 emergence likely resulted from multiple zoonotic events.
Persistent Disparities in COVID-19 Antiviral Dispensing
Communities most at risk of severe COVID-19 outcomes have half the rate of prescriptions compared with less vulnerable communities, according to a CDC report.
Evusheld Reduces COVID-19 Disease Severity Among Unvaccinated Adults
Tixagevimab plus cilgavimab, a SARS-CoV-2–neutralizing monoclonal antibody combination marketed as Evusheld, protected nonhospitalized individuals with mild to moderate COVID-19 symptoms from progressing to severe COVID-19 or death in a clinical trial. The study, published in The Lancet Respiratory Medicine, is the first to evaluate the intramuscular injection for outpatient treatment; other anti–SARS-CoV-2 monoclonal antibodies must be administered intravenously or subcutaneously.
July 25, 2022
Background In a context of multiple Omicron lineages circulation, it is relevant to clarify the effect of vaccination and previous infections on the risk of infection and severe post-infection outcomes. Methods Using electronic health records and SARS-CoV-2 laboratory surveillance data, we conducted a case-case and a cohort study covering the period of Omicron BA.2/BA.5 lineage replacement in Portugal, to compare vaccine effectiveness of complete primary and booster dose against infection, COVID-19 hospitalization, and mortality. Variant classification was performed through whole-genome sequencing (WGS) or Spike Gene Target Failure (SGTF). Findings Between April 25 and June 10, 2022, within a total of 27702 collected samples, 55.5% were classified as BA.2 and the remaining as BA.5. We observed no evidence of reduced vaccine effectiveness for the primary complete vaccination (OR=1.07, CI95%:0.93-1.23) or booster dose vaccination (OR=0.96, CI95%:0.84-1.09) against BA.5 infection compared with BA.2. The protection against reinfection was inferior in BA.5 cases when compared with BA.2 (OR=1.44; CI95%:1.30-1.60). Among those infected with BA.5, booster vaccination was associated with 77% and 88% of reduction in risk of COVID-19 hospitalization and death, respectively, while higher risk reduction was found for BA.2 cases, with 93% and 94%, respectively. Interpretation This study shows that the SARS-CoV-2 Omicron BA.5 lineage is associated with higher odds of reinfection compared with Omicron BA.2, regardless of the vaccination status. Although less effective compared with BA.2, COVID-19 booster vaccination still offers substantial protection against severe outcomes following BA.5 infection.
Symptoms and risk factors for long COVID in non-hospitalized adults
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02–8.39), hair loss (3.99, 3.63–4.39), sneezing (2.77, 1.40–5.50), ejaculation difficulty (2.63, 1.61–4.28) and reduced libido (2.36, 1.61–3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.
SARS-CoV-2 impairs interferon production via NSP2-induced repression of mRNA translation
A robust antiviral innate immune response is indispensable for combating infections. However, an exacerbated response can result in pathological inflammation and tissue damage. mRNA translational control mechanisms play a crucial role in maintaining the appropriate magnitude and duration of the immune response. We show that the GIGYF2/4EHP translational repressor complex represses translation of Ifnb1 mRNA, which encodes type I interferon β (IFN-β). We also demonstrate that the NSP2 protein encoded by SARS-CoV-2 virus further impedes translation of Ifnb1 mRNA through coopting the GIGYF2/4EHP complex, leading to evasion of a cellular innate immune response. The knowledge of the mechanism of action of NSP2-mediated IFN-β suppression provides valuable information for development of treatments for infections of SARS-CoV-2 and other coronaviruses.
Preventive Medication for COVID-19 Infection
Tixagevimab-cilgavimab is a combination medication to help prevent COVID-19 infection. Tixagevimab-cilgavimab (Evusheld) consists of 2 long-acting monoclonal antibodies that bind to the spike protein of the virus that causes COVID-19 to prevent it from infecting human cells.
July 22, 2022
Post–COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection
In this cohort study of 1884 SARS-CoV-2–positive children with 90-day follow-up, 5.8% of patients, including 9.8% of hospitalized children and 4.6% of discharged children, reported PCCs. Characteristics associated with PCCs included being hospitalized 48 hours or more, having 4 or more symptoms reported at the index ED visit, and being 14 years of age or older. In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older.
Children between the ages of 6 months and 5 years of age finally became eligible for COVID-19 vaccination in the U.S. on June 18, after the Director of the Centers for Disease Control and Prevention (CDC) recommended their use for this population, following emergency use authorization granted by the Food and Drug Administration. We recently wrote about some of the issues to consider in vaccinating young children, ranging from fewer access points and more reticence among their parents, compared to their 5-11 year-old counterparts. Here, we examine the status of vaccine uptake in this group, one month into their eligibility. Our analysis is based on data obtained from CDC’s Data Tracker on the number of first COVID-19 doses administered by age as of July 20, 2022 nationally and by jurisdiction (see methods below for more information). Overall, we find that vaccination has already peaked in the youngest age group, and is far below where 5-11 year-olds (who became eligible in November of last year) were at this point in their eligibility:
July 21, 2022
Operation Nasal Vaccine—Lightning speed to counter COVID-19
As the virus continues its accelerated ability to evade our immune response and increase its transmissibility, we urgently need to achieve population-wide respiratory mucosal immunity. The objective of breaking the chain of transmission at the individual and population level will put us in a far better position to achieve containment of the virus, no less reducing the toll of sickness and long COVID-19. The prospect of achieving this with nasal vaccines is high, but will only be possible with dedicated funding, priority, and breaking down of any regulatory hurdles. While we have waited far too long to take such initiative, a new operation at lightning speed could help us get ahead of the virus and build on the initial success of COVID-19 vaccines.
Duration of Shedding of Culturable Virus in SARS-CoV-2 Omicron (BA.1) Infection
The B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a shorter incubation period and a higher transmission rate than previous variants. Recently, the Centers for Disease Control and Prevention recommended shortening the strict isolation period for infected persons in non–health care settings from 10 days to 5 days after symptom onset or after the initial positive test, followed by 5 days of masking. However, the viral decay kinetics of the omicron variant and the duration of shedding of culturable virus have not been well characterized.
Omicron SARS-CoV-2 Neutralization from Inactivated and ZF2001 Vaccines
In the third year of the coronavirus disease 2019 (Covid-19) pandemic, the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has swept the globe and yielded several subvariants. Currently, BA.2 is overtaking BA.1 in frequency. In addition, BA.2.12.1 infection is increasing quickly and already accounts for more than 50% of new infections in the United States. Therefore, the protection of current vaccines and the need to develop future vaccination strategies are of great concern.
July 20, 2022
Efficacy of Antibodies and Antiviral Drugs against Omicron BA.2.12.1, BA.4, and BA.5 Subvariants
As of June 2022, the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been divided into five distinct sublineages: BA.1, BA.2, BA.3, BA.4, and BA.5. Most circulating omicron variants belong to sublineage BA.2; however, the prevalence of BA.2.12.1 (a subvariant of BA.2), BA.4, and BA.5 is increasing rapidly in several regions of the world.2 Previous studies have shown that the BA.2 subvariants have sensitivities to some monoclonal and polyclonal antibodies that are lower than those of the ancestral strains and other SARS-CoV-2 variants.
Tunneling nanotubes provide a route for SARS-CoV-2 spreading
Neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represent a major issue in long coronavirus disease. How SARS-CoV-2 gains access to the brain and how infection leads to neurological symptoms are not clear because the principal means of viral entry by endocytosis, the angiotensin-converting enzyme 2 receptor, are barely detectable in the brain. We report that human neuronal cells, nonpermissive to infection through the endocytic pathway, can be infected when cocultured with permissive infected epithelial cells. SARS-CoV-2 induces the formation of tunneling nanotubes (TNTs) and exploits this route to spread to uninfected cells. In cellulo correlative fluorescence and cryo–electron tomography reveal that SARS-CoV-2 is associated with TNTs between permissive cells. Furthermore, multiple vesicular structures such as double-membrane vesicles, sites of viral replication, are observed inside TNTs between permissive and nonpermissive cells. Our data highlight a previously unknown mechanism of SARS-CoV-2 spreading, likely used as a route to invade nonpermissive cells and potentiate infection in permissive cells.
Effectiveness of BNT162b2 Vaccine against Omicron in Children 5 to 11 Years of Age
A total of 255,936 children were included in the analysis. Among unvaccinated children, the crude incidence rates of all reported SARS-CoV-2 infections, PCR-confirmed SARS-CoV-2 infections, and Covid-19–related hospitalizations were 3303.5, 473.8, and 30.0 per 1 million person-days, respectively. Among partially vaccinated children, vaccine effectiveness was 13.6% (95% confidence interval [CI], 11.7 to 15.5) against all SARS-CoV-2 infections, 24.3% (95% CI, 19.5 to 28.9) against PCR-confirmed SARS-CoV-2 infection, and 42.3% (95% CI, 24.9 to 55.7) against Covid-19–related hospitalization; in fully vaccinated children, vaccine effectiveness was 36.8% (95% CI, 35.3 to 38.2), 65.3% (95% CI, 62.0 to 68.3), and 82.7% (95% CI, 74.8 to 88.2), respectively.
Protection Associated with Previous SARS-CoV-2 Infection in Nicaragua
The course of the current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will be determined in part by the quality and durability of protective immunity induced by previous infection, vaccination, or both, as well as by the severity of illness in persons with some level of immunity.1,2 From March 2020 through October 2021 in the Household Influenza Cohort Study (HICS) study, we followed 2353 participants, ranging in age from newborn infants to elderly persons up to 94 years of age, in 437 households in Nicaragua for the presence of SARS-CoV-2 infection (Figure 1A).
July 20, 2022
Evasion of neutralizing antibodies by Omicron sublineage BA.2.75
One emerging sublineage, BA.2.75, is increasing in frequency in India and has been detected in at least 15 countries as of 19 July 2022. Relative to BA.2, BA.2.75 carries nine additional mutations in spike. Here we report the sensitivity of the BA.2.75 spike to neutralization by a panel of clinically-relevant and pre-clinical monoclonal antibodies, as well as by serum from blood donated in Stockholm, Sweden, before and after the BA.1/BA.2 infection wave. BA.2.75 does not show greater immune evasion than the currently-dominating BA.5 in our set of serum samples, and exhibits moderate susceptibility to tixagevimab and cilgavimab that form a widely used monoclonal antibody cocktail (Evusheld).
July 19, 2022
Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines
The SARS-CoV-2 Omicron variant of concern comprises several sublineages with BA.2 and BA.2.12.1 having replaced the previously dominant BA.1, and BA.4 and BA.5 increasing in prevalence worldwide. We show that the large number of Omicron sublineage spike mutations lead to enhanced ACE2 binding, reduced fusogenicity, and severe dampening of plasma neutralizing activity elicited by infection or seven clinical vaccines relative to the ancestral virus. Administration of a homologous or heterologous booster based on the Wuhan-Hu-1 spike sequence markedly increased neutralizing antibody titers and breadth against BA.1, BA.2, BA.2.12.1, and BA.4/5 across all vaccines evaluated. Our data suggest that although Omicron sublineages evade polyclonal neutralizing antibody responses elicited by primary vaccine series, vaccine boosters may provide sufficient protection against Omicron-induced severe disease.
Cardiometabolic outcomes up to 12 months after COVID-19 infection. A matched cohort study in the UK
In this study, we found that CVD was increased early after COVID-19 mainly from pulmonary embolism, atrial arrhythmias, and venous thromboses. DM incidence remained elevated for at least 12 weeks following COVID-19 before declining. People without preexisting CVD or DM who suffer from COVID-19 do not appear to have a long-term increase in incidence of these conditions.
FDA Authorizes Pharmacists to Prescribe Oral Antiviral Medication for COVID-19
The US Food and Drug Administration (FDA) has revised the Emergency Use Authorization (EUA) for nirmatrelvir/ritonavir, commonly known as Paxlovid, to allow state-licensed pharmacists to prescribe the medication to eligible patients with COVID-19 who are at high risk of progressing to severe disease, with certain limitations. The action is expected to widen access to the drug during the brief period after the onset of symptoms when it is effective.
Respiratory mucosal immunity against SARS-CoV-2 following mRNA vaccination
SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether it elicits effective immune responses in the respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared the SARS-CoV-2 S-specific total and neutralizing antibody responses, and B and T cell immunity, in the bronchoalveolar lavage fluid (BAL) and blood of COVID-19 vaccinated individuals and hospitalized patients. Vaccinated individuals had significantly lower levels of neutralizing antibody against D614G, Delta (B.1.617.2) and Omicron BA.1.1 in the BAL compared to COVID-19 convalescents, despite robust S-specific antibody responses in the blood. Furthermore, mRNA vaccination induced circulating S-specific B and T cell immunity, but in contrast to COVID-19 convalescents, these responses were absent in the BAL of vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic mRNA vaccination alone induced weak respiratory mucosal neutralizing antibody responses, especially against SARS-CoV-2 Omicron BA.1.1 in mice; however, a combination of systemic mRNA vaccination plus mucosal adenovirus-S immunization induced strong neutralizing antibody responses, not only against the ancestral virus but also the Omicron BA.1.1 variant. Together, our study supports the contention that the current COVID-19 vaccines are highly effective against severe disease development, likely through recruiting circulating B and T cell responses during re-infection, but offer limited protection against breakthrough infection, especially by Omicron sublineage. Hence, mucosal booster vaccination is needed to establish robust sterilizing immunity in the respiratory tract against SARS-CoV-2, including infection by Omicron sublineage and future VOCs.
Immune memory to Common Cold Coronaviruses (CCCs) influences SARS-CoV-2 infection outcome, and understanding its effect is crucial for pan-coronavirus vaccine development. We performed a longitudinal analysis of pre-COVID19-pandemic samples from 2016-2019 in young adults and assessed CCC-specific CD4+ T cell and antibody responses. Notably, CCC responses were commonly detected with comparable frequencies as other common antigens and were sustained over time. CCC-specific CD4+ T cell responses were associated with low HLA-DR+CD38+ signals and their magnitude did not correlate with yearly CCC infection prevalence. Similarly, CCC-specific spike RBD-specific IgG responses were stable in time. Finally, high CCC-specific CD4+ T cell reactivity, but not antibody titers, was associated with pre-existing SARS-CoV-2 immunity. These results provide a valuable reference for understanding immune response to endemic coronaviruses and suggest that steady and sustained CCC responses are likely from a stable pool of memory CD4+ T cells, due to repeated earlier exposures and possibly occasional reinfections.
July 18, 2022
Despite bebtelovimab's crucial interest related to COVID-19 treatment strategy, as a single intravenous dose administered in 30 s with no drug–drug interactions, it has not been submitted to regulatory authorities anywhere outside the USA, either for clinical care or for research purposes. However, Eli Lilly has just decided to supply an additional 150 000 doses of bebtelovimab solely to the US Government.
In SARS-CoV-2, astrocytes are in it for the long haul
The most dire consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may not manifest during the initial infection but appear later and are disproportionately associated with compromised neural function. Central nervous system (CNS) complications often appear after the acute phase but persist and become prominent later and last for weeks to months (i.e., long COVID).
Viral variant-resolved wastewater surveillance of SARS-CoV-2 at national scale
SARS-CoV-2 surveillance by wastewater-based epidemiology is poised to provide a complementary approach to sequencing individual cases. However, robust quantification of variants and de novo detection of emerging variants remains challenging for existing strategies. We deep sequenced 3,413 wastewater samples representing 94 municipal catchments, covering >59% of the population of Austria, from December 2020 to February 2022. Our system of variant quantification in sewage pipeline designed for robustness (termed VaQuERo) enabled us to deduce the spatiotemporal abundance of predefined variants from complex wastewater samples. These results were validated against epidemiological records of >311,000 individual cases. Furthermore, we describe elevated viral genetic diversity during the Delta variant period, provide a framework to predict emerging variants and measure the reproductive advantage of variants of concern by calculating variant-specific reproduction numbers from wastewater. Together, this study demonstrates the power of national-scale WBE to support public health and promises particular value for countries without extensive individual monitoring.
The NHS is not living with covid, it’s dying from it
Above all, the government must stop gaslighting the public and be honest about the threat the pandemic still poses to them and the NHS. Being honest with the public will have two positive results, it will encourage the public to modify behaviour and, we hope, provoke urgent reflection about how the NHS is in such a mess so soon after the nation was applauding it on their doorsteps.
We found a high protection against BA.5 from prior omicron infection in triple-vaccinated individuals, and similar vaccine effectiveness for BA.5 infection as currently for BA.2. In an analysis adjusted for covariates, BA.5 infection was associated with an increased risk of hospitalisation which needs confirmation and continued surveillance as hospitalisations were low and stable during the study period.
July 17, 2022
SARS-CoV-2 Omicron rapidly outcompeted other variants and currently dominates the COVID-19 pandemic. Its enhanced transmission and immune evasion are thought to be driven by numerous mutations in the Omicron Spike protein. Here, we systematically introduced BA.1 and/or BA.2 Omicron Spike mutations into the ancestral Spike protein and examined impacts on Spike function, processing and susceptibility to neutralization. Individual mutations of S371F/L, S375F and T376A in the ACE2 receptor-binding domain as well as Q954H and N969K in the hinge region 1 impaired infectivity, while changes of G339D, D614G, N764K and L981F moderately enhanced it. Most mutations in the N-terminal region and the receptor binding domain reduced sensitivity of the Spike protein to neutralization by sera from individuals vaccinated with the BNT162b2 vaccine and by therapeutic antibodies. Our results represent a systematic functional analysis of Omicron Spike adaptations that have allowed this SARS-CoV-2 variant to dominate the current pandemic.
Novavax NVX-COV2373 triggers potent neutralization of Omicron sub-lineages
The SARS-CoV-2 Omicron (B.1.1.529) Variant of Concern (VOC) and its sub-lineages (including BA.2, BA.4/5, BA.2.12.1) contain spike mutations that confer high level resistance to neutralizing antibodies. The NVX-CoV2373 vaccine, a protein nanoparticle vaccine, has value in countries with constrained cold-chain requirements. Here we report neutralizing titers following two or three doses of NVX-CoV2373. We show that after two doses, Omicron sub-lineages BA.1 and BA.4 were resistant to neutralization by 72% (21/29) and 59% (17/29) of samples. However, after a third dose of NVX-CoV2373, we observed high titers against Omicron BA.1 (GMT: 1,197) and BA.4 (GMT: 582), with responses similar in magnitude to those triggered by three doses of an mRNA vaccine. These data are of particular relevance as BA.4 is emerging to become the dominant strain in many locations, and highlight the potential utility of the NVX-CoV2373 vaccine as a booster in resource-limited environments.
July 15, 2022
Among presumed immunocompromised persons aged ≥12 years, local and systemic reactions were less frequently reported to v-safe after mRNA booster (dose 4) than after primary series dose 3. Only 17 serious adverse events were reported to VAERS. Serious adverse events after mRNA booster (dose 4) are rare. Immunocompromised persons aged ≥12 years should receive a first booster ≥3 months after a 3-dose primary COVID-19 vaccination series and a second booster ≥4 months after the first booster.
Reactogenicity of Simultaneous COVID-19 mRNA Booster and Influenza Vaccination in the US
In this cohort study of self-reported data from 981 099 persons aged 12 years or older, simultaneous administration of a COVID-19 mRNA booster dose and an influenza vaccine was associated with 8% to 11% increases, respectively, in systemic reaction compared with COVID-19 mRNA booster alone. These differences were statistically significant.
Investigating trends in those who experience menstrual bleeding changes after SARS-CoV-2 vaccination
Early in 2021, many people began sharing that they experienced unexpected menstrual bleeding after SARS-CoV-2 inoculation. We investigated this emerging phenomenon of changed menstrual bleeding patterns among a convenience sample of currently and formerly menstruating people using a web-based survey. In this sample, 42% of people with regular menstrual cycles bled more heavily than usual, while 44% reported no change after being vaccinated. Among respondents who typically do not menstruate, 71% of people on long-acting reversible contraceptives, 39% of people on gender-affirming hormones, and 66% of postmenopausal people reported breakthrough bleeding. We found that increased/breakthrough bleeding was significantly associated with age, systemic vaccine side effects (fever and/or fatigue), history of pregnancy or birth, and ethnicity. Generally, changes to menstrual bleeding are not uncommon or dangerous, yet attention to these experiences is necessary to build trust in medicine.
July 14, 2022
SARS-CoV-2 variants may threaten the effectiveness of vaccines and antivirals to mitigate serious COVID-19 disease. This is of most concern in clinically vulnerable groups such as older adults. We analysed 72 sera samples from 37 individuals, aged 70–89 years, vaccinated with two doses of BNT162b2 (Pfizer–BioNTech) 3 weeks apart, for neutralizing antibody responses to wildtype SARS-CoV-2. Between 3 and 20 weeks after the second vaccine dose, neutralizing antibody titres fell 4.9-fold to a median titre of 21.3 (neutralization dose 80%), with 21.6% of individuals having no detectable neutralizing antibodies at the later time point. Next, we examined neutralization of 21 distinct SARS-CoV-2 variant spike proteins with these sera, and confirmed substantial antigenic escape, especially for the Omicron (B.1.1.529, BA.1/BA.2), Beta (B.1.351), Delta (B.1.617.2), Theta (P.3), C.1.2 and B.1.638 spike variants. By combining pseudotype neutralization with specific receptor-binding domain (RBD) enzyme-linked immunosorbent assays, we showed that changes to position 484 in the spike RBD were mainly responsible for SARS-CoV-2 neutralizing antibody escape. Nineteen sera from the same individuals boosted with a third dose of BNT162b2 contained higher neutralizing antibody titres, providing cross-protection against Omicron BA.1 and BA.2. Despite SARS-CoV-2 immunity waning over time in older adults, booster vaccines can elicit broad neutralizing antibodies against a large number of SARS-CoV-2 variants in this clinically vulnerable cohort.
Abrupt decreases in infectivity of SARS-CoV-2 in aerosols
A respiratory virus emitted in an aerosol particle will experience a tough journey with many obstacles before finding a new host where it can cause an infection (Fig. 1). By every second, its chances to replicate decrease due to removal by building ventilation, deposition on surfaces, or loss in infectivity. Thus, the transport of infectious viruses from the exhaled breath of one person to the inhaled air of another typically occurs within a few minutes. During this short time, the aerosol will undergo several transformations because of changing environmental conditions. Nevertheless, due to methodological challenges, we still have a remarkably limited understanding of the relationships between environmental factors and survival of pathogens in aerosols on short timescales. In a study in PNAS, Oswin et al. (1) show that the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can decrease abruptly when aerosol particles move between environments.
One coronavirus infection wards off another — but only if it’s a similar variant
Infection with a pre-Omicron SARS-CoV-2 variant protects against reinfection with a second, although the effect fades almost completely after three years.
The chr12q24.13 locus encoding OAS1–OAS3 antiviral proteins has been associated with coronavirus disease 2019 (COVID-19) susceptibility. Here, we report genetic, functional and clinical insights into this locus in relation to COVID-19 severity. In our analysis of patients of European (n = 2,249) and African (n = 835) ancestries with hospitalized versus nonhospitalized COVID-19, the risk of hospitalized disease was associated with a common OAS1 haplotype, which was also associated with reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in a clinical trial with pegIFN-λ1. Bioinformatic analyses and in vitro studies reveal the functional contribution of two associated OAS1 exonic variants comprising the risk haplotype. Derived human-specific alleles rs10774671-A and rs1131454-A decrease OAS1 protein abundance through allele-specific regulation of splicing and nonsense-mediated decay (NMD). We conclude that decreased OAS1 expression due to a common haplotype contributes to COVID-19 severity. Our results provide insight into molecular mechanisms through which early treatment with interferons could accelerate SARS-CoV-2 clearance and mitigate against severe COVID-19.
July 13, 2022
As compared with a third dose, a fourth dose of an mRNA COVID-19 vaccine, administered during the Omicron era, was associated with reduced risk of death from all causes in residents of LTCFs and in the oldest old during the first two months, after which the protection became slightly lower. These findings suggest that a fourth dose may prevent premature mortality in the oldest and frailest even after the emergence of the Omicron variant, although the timing of vaccination seems to be important with respect to the slight waning observed after two months.
Emergence of immune escape at dominant SARS-CoV-2 killer T-cell epitope
We studied the prevalent cytotoxic CD8 T-cell response mounted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein269-277 epitope (sequence YLQPRTFLL) via the most frequent Human Leukocyte Antigen (HLA) class I worldwide, HLA A∗02. The Spike P272L mutation that has arisen in at least 112 different SARS-CoV-2 lineages to date, including in lineages classified as ‘variants of concern’, was not recognised by the large CD8 T-cell response seen across cohorts of HLA A∗02+ convalescent patients and individuals vaccinated against SARS-CoV-2, despite these responses comprising of over 175 different individual T-cell receptors. Viral escape at prevalent T-cell epitopes restricted by high frequency HLAs may be particularly problematic when vaccine immunity is focussed on a single protein such as SARS-CoV-2 Spike providing a strong argument for inclusion of multiple viral proteins in next generation vaccines and highlighting the need for monitoring T-cell escape in new SARS-CoV-2 variants.
These findings indicate that adolescent and young adult men are at the highest risk of myocarditis after mRNA vaccination. Use of a Pfizer vaccine over a Moderna vaccine and waiting for more than 30 days between doses might be preferred for this population. Incidence of myocarditis in children aged 5-11 years is very rare but certainty was low. Data for clinical risk factors were very limited. A clinical course of mRNA related myocarditis appeared to be benign, although longer term follow-up data were limited. Prospective studies with appropriate testing (eg, biopsy and tissue morphology) will enhance understanding of mechanism.
Clinical Spectrum of Children with Acute Hepatitis of Unknown Cause
In this series involving 44 young children with acute hepatitis of uncertain cause, human adenovirus was isolated in most of the children, but its role in the pathogenesis of this illness has not been established.
A Case Series of Children with Acute Hepatitis and Human Adenovirus Infection
Human adenovirus viremia was present in the majority of children with acute hepatitis of unknown cause admitted to Children’s of Alabama from October 1, 2021, to February 28, 2022, but whether human adenovirus was causative remains unclear. Sequencing results suggest that if human adenovirus was causative, this was not an outbreak driven by a single strain.
July 12, 2022
Broadly neutralizing antibodies target the coronavirus fusion peptide
The potential for future coronavirus outbreaks highlights the need to broadly target this group of pathogens. We use an epitope-agnostic approach to identify six monoclonal antibodies that bind to spike proteins from all seven human-infecting coronaviruses. All six antibodies target the conserved fusion peptide region adjacent to the S2' cleavage site. COV44-62 and COV44-79 broadly neutralize alpha and beta coronaviruses, including SARS-CoV-2 Omicron subvariants BA.2 and BA.4/5, albeit with lower potency than RBD-specific antibodies. In crystal structures of Fabs COV44-62 and COV44-79 with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine at the S2' cleavage site. COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings highlight the fusion peptide as a candidate epitope for next-generation coronavirus vaccine development.
ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies
The coronavirus spike (S) glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune donors seven monoclonal antibodies (mAbs) that bind to all human-infecting coronavirus S proteins. This class of mAbs recognize the fusion peptide and acquire affinity and breadth through somatic mutations. Despite targeting a conserved motif, only some mAbs show broad neutralizing activity in vitro against alpha- and beta-coronaviruses, including animal coronavirus WIV-1 and PDF-2180. Two selected mAbs also neutralize Omicron BA.1 and BA.2 authentic viruses and reduce viral burden and pathology in vivo. Structural and functional analyses show that the fusion peptide-specific mAbs bind with different modalities to a cryptic epitope, which is hidden in prefusion stabilized S, and becomes exposed upon binding of angiotensin-converting enzyme 2 (ACE2) or ACE2-mimicking mAbs.
This study estimates the effectiveness of previous infection with SARSCoV2 in preventing reinfection with Omicron BA.4/BA.5 subvariants using a test negative, case control study design. Cases (SARSCoV2 positive test results) and controls (SARSCoV2 negative test results) were matched according to sex, 10 year age group, nationality, comorbid condition count, calendar week of testing, method of testing, and reason for testing. Effectiveness was estimated using the S gene target failure (SGTF) infections between May 7, 2022 and July 4, 2022. SGTF status provides a proxy for BA.4/BA.5 infections, considering the negligible incidence of other SGTF variants during the study. Effectiveness was also estimated using all diagnosed infections between June 8, 2022 and July 4, 2022, when BA.4/BA.5 dominated incidence. Effectiveness of a previous pre-Omicron infection against symptomatic BA.4/BA.5 reinfection was 15.1% (95% CI: -47.1 to 50.9%), and against any BA.4/BA.5 reinfection irrespective of symptoms was 28.3% (95% CI: 11.4 to 41.9%). Effectiveness of a previous Omicron infection against symptomatic BA.4/BA.5 reinfection was 76.1% (95% CI: 54.9 to 87.3%), and against any BA.4/BA.5 reinfection was 79.7% (95% CI: 74.3 to 83.9%). Results using all diagnosed infections when BA.4/BA.5 dominated incidence confirmed the same findings. Sensitivity analyses adjusting for vaccination status confirmed study results. Protection of a previous infection against BA.4/BA.5 reinfection was modest when the previous infection involved a preOmicron variant, but strong when the previous infection involved the Omicron BA.1 or BA.2 subvariants. Protection of a previous infection against BA.4/BA.5 was lower than that against BA.1/BA.2, consistent with BA.4/BA.5 greater capacity for immune system evasion than that of BA.1/BA.2.
Enhanced innate immune suppression by SARS-CoV-2 Omicron subvariants BA.4 and BA.5
SARS-CoV-2 adaptation to its human host is evidenced by the emergence of new viral lineages with distinct genotypic and phenotypic characteristics, termed variants of concern (VOCs). Particular VOCs have become sequentially dominant globally (Alpha, Delta, Omicron) with each evolving independently from the ancestral Wuhan strain. Omicron is notable for its large number of Spike mutations found to promote immune escape and re-infection. Most recently, Omicron BA.4 and BA.5 subvariants have emerged with increasing levels of adaptive immune escape threatening vaccine effectiveness and increasing hospitalisations. Here, we demonstrate that the most recent Omicron variants have enhanced capacity to antagonise or evade human innate immune defenses. We find Omicron BA.4 and BA.5 replication is associated with reduced activation of epithelial innate immune responses versus earlier BA.1 and BA.2 subvariants. We also find enhanced expression of innate immune antagonist proteins Orf6 and N, similar to Alpha, suggesting common pathways of human adaptation and linking VOC dominance to improved innate immune evasion. We conclude that Omicron BA.4 and BA.5 have combined evolution of antibody escape with enhanced antagonism of human innate immunity to improve transmission and possibly reduce immune protection from severe disease.
Universal healthcare and the pandemic mortality gap
Canada and the United States are wealthy federal democracies that share ties of history, culture, language, and the world’s longest undefended border. However, the countries are not identical, and this truth has been underlined during the recent pandemic. As Galvani et al. (1) note in PNAS, Canada’s response to the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been far more successful at preserving life and health than the US response, with per-capita SARS-CoV-2 attributed mortality around 3 times higher in the United States than in Canada. The authors suggest that is due, in part, to an important difference between Canada and the United States: Canada has universal, single-payer health insurance; the US health insurance system is a patchwork, with millions of individuals uninsured, or underinsured.
Tropism of SARS-CoV-2 for human cortical astrocytes
Neurological and neuropsychiatric symptoms occur in as many as one-third of patients with or recovering from COVID-19. To address severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neural tropism, we evaluated the vulnerability of primary developing and adult cortical tissue and stem-cell-derived cortical organoids to SARS-CoV-2 infection. We observe robust infection and viral replication in human cortical astrocytes; they become reactive, have increased growth factor signaling, and activate cellular stress. Despite infection in astroglial cells, there is minimal infection of other neural cell types, including neurons. Surprisingly, we discover that astrocyte infection is unlikely to be mediated by the predominant coronavirus receptor, ACE2, and instead observe alternative glycoproteins, CD147 and DPP4, expressed on astrocytes; they are necessary and sufficient for SARS-CoV-2 infection.
July 11, 2022
Paxlovid Resistance: Is It Just a Matter of Time Now?
Pfizer’s coronavirus protease inhibitor Paxlovid (nirmatrelvir and ritonavir) is being widely used now, and it’s been clear since the beginning that resistant strains of the virus could appear against it. After all, that’s what viruses do. With their vast numbers, fast generation time, and number of mutations, resistance to a given small molecule is generally just a matter of “when”, not “if”. The usual way around this problem is to try to use a drug cocktail, hitting the pathogen simultaneously with compounds that target more than one mechanism. That’s the idea behind the two most successful small-molecule viral therapies we have, against HIV and Hepatitis C.
SARS-CoV-2 infection and the brain: direct evidence for brain changes in milder cases
Currently, many restrictions and protective measures are relaxed because Omicron is highly transmissible but usually causes mild to moderate acute disease. This raises hope that SARS-CoV-2 may evolve towards reduced pathogenicity and become similar to circulating coronaviruses causing mild respiratory infections. More work needs to be done to clarify whether the current Omicron and future variants of SARS-CoV-2 may also cause lasting brain abnormalities and whether these can be prevented by vaccination or therapy. However, the finding by Douaud and colleagues1 that SARS-CoV-2 causes structural changes in the brain that may be permanent and could relate to neurological decline is of concern and illustrates that the pathogenesis of this virus is markedly different from that of circulating human coronaviruses. Further studies, to elucidate the mechanisms underlying COVID-19-associated neurological abnormalities and how to prevent or reverse them are urgently needed.
July 10, 2022
The infectivity of virus in primary swabs and expanded isolates revealed whilst BA.1 and BA.2 are attenuated through ACE2/TMPRSS2, BA.5 infectivity is equivalent to that of an early 2020 circulating clade and has greater sensitivity to the TMPRSS2 inhibitor Nafamostat. As with BA.1, we observed BA.5 to significantly reduce neutralisation titres across all donors. Concentrated pooled human IgG from convalescent and vaccinated donors had greater breadth of neutralisation, although the potency was still reduced 7-fold with BA.5. Of all therapeutic antibodies tested, we observed a 14.3-fold reduction using Evusheld and 16.8 reduction using Sotrovimab when neutralising a Clade A versus BA.5 isolate. These results have implications for ongoing tracking and management of Omicron waves globally.
July 9, 2022
The present analysis included 223 individuals recovered from mainly mild to moderate SARS-CoV-2 infections (100 female/123 male, age [years], mean +- SD, 55.54 +- 7.07) and 223 matched healthy controls (93 female/130 male, 55.74 +- 6.60). Among all 11 MR imaging markers tested, significant differences between groups were found in global measures of mean diffusivity and extracellular free-water which were both elevated in the white matter of post-SARS-CoV-2 individuals comparing to matched controls (free-water: 0.148 +- 0.018 vs. 0.142 +- 0.017, P<.001; mean diffusivity [10-3 mm2/s]: 0.747 +- 0.021 vs. 0.740 +- 0.020, P<.001). Classification accuracy for detecting post-SARS-CoV-2 individuals based on diffusion imaging markers was up to 80%. Neuropsychological test scores did not significantly differ between groups. Conclusions and Relevance: Our findings suggest that subtle changes in white matter extracellular water content may last beyond the acute infection with SARS-CoV-2. However, in our sample, a mild to moderate SARS-CoV-2 infection was not associated with neuropsychological deficits, significant changes in cortical structure or vascular lesions several months after recovery. External validation of our findings and longitudinal follow-up investigations are needed.
July 8, 2022
Immunocompromised patients accounted for 12.2% of all adult COVID-19 hospitalizations among 10 states and had increased odds of ICU admission and in-hospital death compared with nonimmunocompromised patients, irrespective of vaccination status. Known multilayered prevention measures, including nonpharmaceutical interventions, up-to-date COVID-19 vaccination, and therapeutics, can prevent hospitalization and subsequent severe COVID-19 outcomes among immunocompromised persons.
Immune determinants of chronic sequelae after respiratory viral infection
The acute effects of various respiratory viral infections have been well studied, with extensive characterization of the clinical presentation as well as viral pathogenesis and host responses. However, over the course of the recent COVID-19 pandemic, the incidence and prevalence of chronic sequelae after acute viral infections have become increasingly appreciated as a serious health concern. Post-acute sequelae of COVID-19, alternatively described as “long COVID-19,” are characterized by symptoms that persist for longer than 28 days after recovery from acute illness. Although there exists substantial heterogeneity in the nature of the observed sequelae, this phenomenon has also been observed in the context of other respiratory viral infections including influenza virus, respiratory syncytial virus, rhinovirus, severe acute respiratory syndrome coronavirus, and Middle Eastern respiratory syndrome coronavirus. In this Review, we discuss the various sequelae observed following important human respiratory viral pathogens and our current understanding of the immunological mechanisms underlying the failure of restoration of homeostasis in the lung.
COVID variants found in sewage weeks before showing up in tests
Researchers in California have flushed a wealth of data out of toilet waste. For the first time, scientists have been able to detect specific variants of SARS-CoV-2 in sewage weeks before they were showing up in testing clinics.
July 7, 2022
Wastewater sequencing reveals early cryptic SARS-CoV-2 variant transmission
As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases1–3. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing4,5. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.
A subset of individuals who recover from coronavirus disease 2019 (COVID-19) develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal tissue samples. The mouse-adapted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain MA10 produces an acute respiratory distress syndrome (ARDS) in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute to clinical recovery phases. At 15 to 120 days post-virus clearance, pulmonary histologic findings included subpleural lesions composed of collagen, proliferative fibroblasts, and chronic inflammation, including tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal up-regulation of pro-fibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early anti-fibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC.
July 6, 2022
SARS-CoV-2 spreads via droplets, aerosols, and smear infection. From the beginning of the COVID-19 pandemic, using a facemask in different locations was recommended to slow down the spread of the virus. To evaluate facemasks' performance, masks' filtration efficiency is tested for a range of particle sizes. Although such tests quantify the blockage of the mask for a range of particle sizes, the test does not quantify the cumulative amount of virus-laden particles inhaled or exhaled by its wearer. In this study, we quantify the accumulated viruses that the healthy person inhales as a function of time, activity level, type of mask, and room condition using a physics-based model. We considered different types of masks, such as surgical masks and filtering facepieces (FFPs), and different characteristics of public places such as office rooms, buses, trains, and airplanes. To do such quantification, we implemented a physics-based model of the mask. Our results confirm the importance of both people wearing a mask compared to when only one wears the mask. The protection time before the healthy wearer has an infection risk of 50% reduces by 80% if only one wears the facemask instead of both people. The protection time is further reduced if the infected person starts to cough or increases the activity level by 85% and 99%, respectively. Results show the leakage of the mask can considerably affect the performance of the mask. For the surgical mask, the apparent filtration efficiency reduces by 75% with such a leakage, which cannot provide sufficient protection despite the high filtration efficiency of the mask. The facemask model presented provides key input in order to evaluate the protection of masks for different conditions in public places. The physics-based model of the facemask is provided as an online application.
SARS-CoV-2 Omicron sublineages exhibit distinct antibody escape patterns
SARS-CoV-2 neutralizing antibodies play a critical role in COVID-19 prevention and treatment but are challenged by viral evolution and the emergence of novel escape variants. Importantly, the recently identified Omicron sublineages BA.2.12.1 and BA.4/5 are rapidly becoming predominant in various countries. By determining polyclonal serum activity of 50 convalescent or vaccinated individuals against BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.4/5, we reveal a further reduction of BA.4/5 susceptibility to vaccinee sera. Most notably, delineation of sensitivity to an extended 163-antibody panel demonstrates pronounced antigenic differences with distinct escape patterns among Omicron sublineages. Antigenic distance and/or higher resistance may therefore favor immune escape-mediated BA.4/5 expansion after the first Omicron wave. Finally, while most clinical-stage monoclonal antibodies are inactive against Omicron sublineages, we identify promising antibodies with high pan-SARS-CoV-2 neutralizing potency. Our study provides a detailed understanding of Omicron sublineage antibody escape that can inform on effective strategies against COVID-19.
Past SARS-CoV-2 Infection Protection Against Reinfection: A Systematic Review and Meta-Analysis
We identified a total of 43 studies from 17 different countries. Our meta-analyses show that protection from recent infection and any symptomatic disease was high for ancestral, Alpha, Beta, and Delta variants but was substantially lower for the Omicron variant. Pooled effectiveness against reinfection by the Omicron variant was 38.8% (95% uncertainty interval [UI] 31.5–46.3) and 43.7% (18.4–74.4) against Omicron symptomatic disease. Mean pooled effectiveness was greater than 85% against severe disease (hospitalisation and death) for all variants, including Omicron. Protection from reinfection from ancestral, Alpha, and Delta variants declined over time but remained at 78.2% (38.9–95.1) at 40 weeks. Protection against reinfection by the Omicron variant declined more rapidly and was estimated at 29.0% (10.4–64.4) at 40 weeks. There were not enough data to estimate protection against symptomatic disease and severe disease considering time since infection.
July 5, 2022
Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models
To combat future SARS-CoV-2 variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles presenting randomly-arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes that are conserved and relatively occluded, rather than variable, immunodominant, and exposed. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD-nanoparticles in mice and macaques, observing stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants including Omicrons and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest mosaic-8 RBD-nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers.
COVID-19 Neuropathology: evidence for SARS-CoV-2 invasion of Human Brainstem Nuclei
Neurological manifestations are common in COVID-19, the disease caused by SARS-CoV-2. Despite reports of SARS-CoV-2 detection in the brain and cerebrospinal fluid of COVID-19 patients, it's still unclear whether the virus can infect the central nervous system, and which neuropathological alterations can be ascribed to viral tropism, rather than immune mediated mechanisms. Here, we assess neuropathology alterations in 24 COVID-19 patients and 18 matched controls who died due to pneumonia / respiratory failure. Aside from a wide spectrum of neuropathological alterations, SARS-CoV-2-immunoreactive neurons were detected in specific brainstem nuclei of 5 COVID-19 subjects. Viral RNA was also detected by real-time RT-PCR. Quantification of reactive microglia revealed an anatomically segregated pattern of inflammation within affected brainstem regions, and was higher when compared to controls. While the results of this study support the neuroinvasive potential of SARS-CoV-2, the role of SARS-CoV-2 neurotropism in COVID-19 and its long-term sequelae require further investigation.
Neurovascular injury with complement activation and inflammation in COVID-19
Antibody-mediated cytotoxicity directed against the endothelial cells is the most likely initiating event that leads to vascular leakage, platelet aggregation, neuroinflammation and neuronal injury. Therapeutic modalities directed against immune complexes should be considered.
Leading Causes of Death in the US During the COVID-19 Pandemic, March 2020 to October 2021
From March 2020 to October 2021, COVID-19 accounted for 1 in 8 deaths in the US and was a top 5 cause of death in every age group aged 15 years and older. Cancer and heart disease deaths exceeded COVID-19 deaths overall and in most age groups, whereas accidents were the leading cause of death among those aged 1 to 44 years. Compared with the 2020 time period, deaths from COVID-19 in the 2021 time period decreased in ranking among those aged 85 years or older but increased in ranking among those aged 15 to 54 years, and became the leading cause of death among those aged 45 to 54 years. The increased ranking of COVID-19 as a leading cause of death in some age groups is consistent with a downward age shift in the distribution of COVID-19 deaths in the US in 2021 compared with 2020, perhaps driven by higher COVID-19 vaccination rates in 2021 in the oldest age groups.
Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4, & BA.5
SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged dramatically to become dominant in the United States and South Africa, respectively1,2. These novel subvariants carrying additional mutations in their spike proteins raise concerns that they may further evade neutralizing antibodies, thereby further compromising the efficacy of COVID-19 vaccines and therapeutic monoclonals. We now report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. However, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike residue L452 found in both BA.2.12.1 and BA.4/5 facilitates escape from some antibodies directed to the so-called class 2 and 3 regions of the receptor-binding domain3. The F486V mutation found in BA.4/5 facilitates escape from certain class 1 and 2 antibodies but compromises the spike affinity for the viral receptor. The R493Q reversion mutation, however, restores receptor affinity and consequently the fitness of BA.4/5. Among therapeutic antibodies authorized for clinical use, only bebtelovimab retains full potency against both BA.2.12.1 and BA.4/5. The Omicron lineage of SARS-CoV-2 continues to evolve, successively yielding subvariants that are not only more transmissible but also more evasive to antibodies.
July 4, 2022
Protease inhibitors are among the most powerful antiviral drugs. A first protease inhibitor against the SARS-CoV-2 protease 3CLpro, Paxlovid (nirmatrelvir / ritonavir), has recently been authorized by the U.S. FDA for emergency use (EUA 105 Pfizer Paxlovid). To find resistant mutants against the protease-inhibitor-component of Paxlovid, nirmatrelvir, we engineered a chimeric Vesicular Stomatitis Virus (VSV). By replacing an intergenic region, which is essential for separate gene transcription, with 3CLpro, this chimeric VSV became dependent on the protease to process two of its genes. We then applied selective pressure with nirmatrelvir to induce mutations. The effect of those mutants was confirmed by re-introduction in the 3CLpro and testing with a recently developed cellular assay. Furthermore, we found that mutations predicted by our method already exist in SARS-CoV-2 sequence depositions in NCBI and GISAID data bases. These may represent emerging resistant virus variants or a natural heterogeneity in the susceptibility to nirmatrelvir.
The first two mRNA vaccines against infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that were approved by regulators require a cold chain and were designed to elicit systemic immunity via intramuscular injection. Here we report the design and preclinical testing of an inhalable virus-like-particle as a COVID-19 vaccine that, after lyophilisation, is stable at room temperature for over three months. The vaccine consists of a recombinant SARS-CoV-2 receptor-binding domain (RBD) conjugated to lung-derived exosomes which, with respect to liposomes, enhance the retention of the RBD in both the mucus-lined respiratory airway and in lung parenchyma. In mice, the vaccine elicited RBD-specific IgG antibodies, mucosal IgA responses and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile in the animals’ lungs, and cleared them of SARS-CoV-2 pseudovirus after a challenge. In hamsters, two doses of the vaccine attenuated severe pneumonia and reduced inflammatory infiltrates after a challenge with live SARS-CoV-2. Inhalable and room-temperature-stable virus-like particles may become promising vaccine candidates.
July 1, 2022
By April 25, 2022, most U.S. counties had a pharmacy or public health clinic offering COVID-19 vaccines to children aged 5–11 years; fewer counties had a pediatric clinic, family medicine clinic, or federally qualified health center. The availability of each provider type was associated with higher county-level vaccination coverage among children aged 5–11 years.
A 2020 U.S. Public Health Service recommendation to test transplant candidates for HIV, HBV, and HCV during the transplant hospital admission could result in potentially harmful blood loss in pediatric transplant candidates. Children aged <13 years are among those at lowest risk for new HIV infections, and incidence of acute HBV and HCV infection in U.S. residents aged <20 years is extremely low.
In this longitudinal observational study conducted among health care workers with SARS-CoV-2 infections not requiring hospitalization, 2 or 3 doses of vaccine, compared with no vaccination, were associated with lower long COVID prevalence. Study limitations include that symptoms and duration were self-reported, and causality cannot be inferred.
In this cohort study of 18 611 residents at 640 long-term care facilities, the risk of SARS-CoV-2 infection, COVID-19–related hospitalizations, and COVID-19–related deaths was 89% to 96% lower among residents who received the third dose of BNT162b2 vaccine compared with vaccinees who received 2 doses at least 5 months earlier during the Delta variant surge in Israel.
Assessment of Resilience Training for Hospital Employees in the Era of COVID-19
In this pilot cohort study of 153 health care workers and hospital employees from a single health system, the group-coaching program was feasible and acceptable, as demonstrated by high demand, retention, and satisfaction. Measured according to validated scales, self-reported resilience, stress, anxiety, and burnout improved among participants.
Analysis of COVID-19–Related Croup and SARS-CoV-2 Variant Predominance in the US
The results of this cross-sectional study expand on recent single-center studies1,2 showing that hospitalizations for COVID-19–related croup increased after the onset of the Omicron variant. A more recent national investigation3 found that the percentage of children diagnosed with SARS-CoV-2 hospitalized with upper-airway infections increased significantly from pre-Omicron (1.4%) compared with Omicron (4.1%) periods. The hospitalization rate was higher in our study, which may be associated with use of ICD-10 codes rather than positive SARS-CoV-2 test results for COVID-19 data. Findings for association with COVID-19–related croup severity were mixed in our study. We noted a significant increase in the proportion of children requiring RE during Alpha or other variant and Omicron periods compared with the period of Delta predominance. However, we also observed no difference in the median number of RE doses, which was comparable to an estimate prior to COVID-19.5 The overall ICU admission rate in our sample was lower than a rate described prior to COVID-19,5 which may be associated with constraints on ICU capacity or, alternatively, less severe illness.
July, 2022
Severe acute hepatitis in children: investigate SARS-CoV-2 superantigens
We hypothesise that the recently reported cases of severe acute hepatitis in children could be a consequence of adenovirus infection with intestinal trophism in children previously infected by SARS-CoV-2 and carrying viral reservoirs (appendix). In mice, adenovirus infection sensitises to subsequent Staphylococcal-enterotoxin-B-mediated toxic shock, leading to liver failure and death.9 This outcome was explained by adenovirus-induced type-1 immune skewing, which, upon subsequent Staphylococcal enterotoxin B administration, led to excessive IFN-γ production and IFN-γ-mediated apoptosis of hepatocytes.9 Translated to the current situation, we suggest that children with acute hepatitis be investigated for SARS-CoV-2 persistence in stool, T-cell receptor skewing, and IFN-γ upregulation, because this could provide evidence of a SARS-CoV-2 superantigen mechanism in an adenovirus-41F-sensitised host. If evidence of superantigen-mediated immune activation is found, immunomodulatory therapies should be considered in children with severe acute hepatitis.
June 30, 2022
Using BMI categories, there is evidence of protection against severe COVID-19 in people with overweight or obesity who have been vaccinated, which was of a similar magnitude to that of people of healthy weight. Vaccine effectiveness was slightly lower in people with underweight, in whom vaccine uptake was also the lowest for all ages. In the vaccinated cohort, there were increased risks of severe COVID-19 outcomes for people with underweight or obesity compared with the vaccinated population with a healthy weight. These results suggest the need for targeted efforts to increase uptake in people with low BMI (<18·5 kg/m2), in whom uptake is lower and vaccine effectiveness seems to be reduced. Strategies to achieve and maintain a healthy weight should be prioritised at the population level, which could help reduce the burden of COVID-19 disease.
Effect of vaccination on household transmission of SARS-CoV-2 Delta variant of concern
Effective vaccines protect individuals by not only reducing the susceptibility to infection, but also reducing the infectiousness of breakthrough infections in vaccinated cases. To disentangle the vaccine effectiveness against susceptibility to infection (VES) and vaccine effectiveness against infectiousness (VEI), we took advantage of Danish national data comprising 24,693 households with a primary case of SARS-CoV-2 infection (Delta Variant of Concern, 2021) including 53,584 household contacts. In this setting, we estimated VES as 61% (95%-CI: 59-63), when the primary case was unvaccinated, and VEI as 31% (95%-CI: 26-36), when the household contact was unvaccinated. Furthermore, unvaccinated secondary cases with an infection exhibited a three-fold higher viral load compared to fully vaccinated secondary cases with a breakthrough infection. Our results demonstrate that vaccinations reduce susceptibility to infection as well as infectiousness, which should be considered by policy makers when seeking to understand the public health impact of vaccination against transmission of SARS-CoV-2.
The response to the COVID-19 pandemic prompted abrupt and potentially lasting changes to human behavior, including the types of direct contact that enable transmission of common pathogens. Although the handshake and other types of physical contact are gradually returning, they have been on an extended hiatus. Such changes have already altered the epidemiology of a broad range of infectious diseases, including influenza, measles, and norovirus, and will likely continue to affect their age distribution, severity, and typical seasonal patterns. Changes to contact patterns may also nudge the evolutionary trajectory of pathogens, as they adapt to new norms of less human contact. Initiatives to measure social contact patterns through time and track their effects on the epidemiology of endemic pathogens are essential to both manage
June 29, 2022
First known case of getting COVID from a cat
Scientists in Thailand have established that a tabby passed SARS-CoV-2 to a veterinary surgeon — although such cases of cat-to-human transmission are probably rare.
Bad news for Paxlovid? Coronavirus can find multiple ways to evade COVID-19 drug
Lab studies identify resistance mutations in SARS-CoV-2’s protease, and some circulating variants have them.
Long distance airborne transmission of SARS-CoV-2: rapid systematic review
This rapid systematic review found evidence suggesting that long distance airborne transmission of SARS-CoV-2 might occur in indoor settings such as restaurants, workplaces, and venues for choirs, and identified factors such as insufficient air replacement that probably contributed to transmission. These results strengthen the need for mitigation measures in indoor settings, particularly the use of adequate ventilation.
Duration of Shedding of Culturable Virus in SARS-CoV-2 Omicron (BA.1) Infection
The B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a shorter incubation period and a higher transmission rate than previous variants.1,2 Recently, the Centers for Disease Control and Prevention recommended shortening the strict isolation period for infected persons in non–health care settings from 10 days to 5 days after symptom onset or after the initial positive test, followed by 5 days of masking.3 However, the viral decay kinetics of the omicron variant and the duration of shedding of culturable virus have not been well characterized.
BNT162b2 Vaccine Effectiveness against Omicron in Children 5 to 11 Years of Age
Among 136,127 eligible children who had been vaccinated during the study period, 94,728 were matched with unvaccinated controls. The estimated vaccine effectiveness against documented infection was 17% (95% confidence interval [CI], 7 to 25) at 14 to 27 days after the first dose and 51% (95% CI, 39 to 61) at 7 to 21 days after the second dose. The absolute risk difference between the study groups at days 7 to 21 after the second dose was 1905 events per 100,000 persons (95% CI, 1294 to 2440) for documented infection and 599 events per 100,000 persons (95% CI, 296 to 897) for symptomatic Covid-19. The estimated vaccine effectiveness against symptomatic Covid-19 was 18% (95% CI, −2 to 34) at 14 to 27 days after the first dose and 48% (95% CI, 29 to 63) at 7 to 21 days after the second dose. We observed a trend toward higher vaccine effectiveness in the youngest age group (5 or 6 years of age) than in the oldest age group (10 or 11 years of age).
Immunogenicity and Safety of Beta-Adjuvanted Recombinant Booster Vaccine
The value of variant-adapted vaccines that are capable of inducing a higher and broader immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at booster vaccination is currently being evaluated.1-4 We conducted a multicenter, randomized, single-blind trial to assess the immunogenicity and safety of two adjuvanted recombinant vaccines and the messenger RNA (mRNA) vaccine BNT162b2 (Pfizer–BioNTech) administered as a booster.
A broad and potent neutralization epitope in SARS-related coronaviruses
Since the beginning of the COVID-19 pandemic, many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged that are resistant to varying extents to neutralizing antibody responses induced by current vaccines and natural infection, especially the recent Omicron variants. Neutralizing potency and breadth for an antibody are often somewhat mutually exclusive. Here, we delineate the molecular interaction between a therapeutic antibody (ADG20) and SARS-CoV-2 receptor-binding domain (RBD) by X-ray crystallography and characterize its binding epitope. We show that this site is targeted by a few rare antibodies that have both potency and breadth. These findings provide insights into the design of more universal vaccines and broad therapeutic antibodies, which are pressingly needed.
June 28, 2022
Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir
The SARS-CoV-2 main protease (Mpro) is a cysteine protease and a validated antiviral drug target. Paxlovid is an FDA-approved oral COVID-19 antiviral that contains the Mpro inhibitor nirmatrelvir and the metabolic booster ritonavir. The emergence of SARS-CoV-2 variants mutations in the Mpro raised the alarm of potential drug resistance. In this study, we aim to discover Mpro drug resistant mutants from naturally observed polymorphisms. Through analyzing the SARS-CoV-2 sequences deposited in Global initiative on Sharing Avian influenza Data (GISAID) database, we identified 66 prevalent Mpro mutations located at the nirmatrelvir binding site. The Mpro mutant proteins were expressed and characterized for enzymatic activity and nirmatrelvir inhibition. While the majority of the Mpro mutants had reduced enzymatic activity (kcat/Km >10-fold decrease), 11 mutants including S144M/F/A/G/Y, M165T, E166Q, H172Q/F, and Q192T/S/V showed comparable enzymatic activity as the wild-type (kcat/Km <10-fold change) and resistance to nirmatrelvir (Ki > 10-fold increase). We further demonstrate that the enzymatic activity and inhibitor resistance of these single mutations can be enhanced by additional substitutions in a double mutant. X-ray crystal structures were determined for six of the single mutants with and/or without GC-376/nirmatrelvir. The structures illustrate how mutations can reduce ligand binding by impacting the conformational stability of the active site. Overall, our study identified several drug resistant hot spots that warrant close monitoring for possible clinical evidence of Paxlovid resistance.
Augmented neutralisation resistance of emerging omicron subvariants BA.2.12.1, BA.4, and BA.5
The SARS-CoV-2 omicron (B.1.1.529) variant is highly resistant against antibody-mediated neutralisation due to many mutations in the spike (S) protein. Several omicron subvariants have been detected, with BA.2.12.1 (first detected in the USA) and BA.4 and BA.5 (first detected in South Africa) currently outcompeting the previously circulating BA.1 and BA.2 subvariants in several countries. The S proteins of BA.4 and BA.5, which are identical on the protein level, and BA.2.12.1 harbour unique mutations (appendix pp 1–2), but it is largely unknown whether they differ from BA.1 and BA.2 regarding neutralisation sensitivity.
The dynamics of SARS-CoV-2 infectivity with changes in aerosol microenvironment
The aerosol microenvironment is dynamic, exposing pathogens, such as severe acute respiratory syndrome coronavirus 2 virus, when exhaled in respiratory aerosol to extreme conditions of solute concentration, pH, and evaporative cooling. Yet surviving this environment is a key step in the transmission of such pathogens. Understanding the impact that airborne transport has on pathogens and the influence of environmental conditions on pathogen survival can inform the implementation of strategies to mitigate the spread of diseases such as coronavirus disease 2019. We report changes in the infectivity of the airborne virus over timescales from 5 s to 20 min and demonstrate the role of two microphysical processes in this infectivity loss, namely, particle crystallization and aerosol droplet pH change.
The availability of three COVID-19 vaccines in the United States provides an unprecedented opportunity to examine how vaccine platforms and timing of vaccination in pregnancy impact maternal and neonatal immunity. Here, we characterize the antibody profile after Ad26.COV2.S, mRNA-1273 or BNT162b2 vaccination in 158 pregnant individuals and evaluate transplacental antibody transfer by profiling maternal and umbilical cord blood in 175 maternal-neonatal dyads. These analyses reveal lower vaccine-induced functions and Fc receptor-binding after Ad26.COV2.S compared to mRNA vaccination and subtle advantages in titer and function with mRNA-1273 versus BN162b2. mRNA vaccines have higher titers and functions against SARS-CoV-2 variants of concern. First and third trimester vaccination results in enhanced maternal antibody-dependent NK-cell activation, cellular and neutrophil phagocytosis, and complement deposition relative to second trimester. Higher transplacental transfer ratios following first and second trimester vaccination may reflect placental compensation for waning maternal titers. These results provide novel insight into the impact of platform and trimester of vaccination on maternal humoral immune response and transplacental antibody transfer.
On June 18, 2022, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for the use of the Moderna COVID-19 vaccine for children aged 6 months–5 years and for the Pfizer-BioNTech COVID-19 vaccine for children aged 6 months–4 years in the United States for prevention of COVID-19. ACIP determined that the benefits of vaccination outweigh risks for this population.
All-Cause Maternal Mortality in the US Before vs During the COVID-19 Pandemic
In the US, maternal deaths increased substantially (33.3%) after March 2020, corresponding to COVID-19 onset, a figure higher than the 22% overall excess death estimate associated with the pandemic.4 Increases were highest for Hispanic and non-Hispanic Black women. Change in maternal deaths during the pandemic may involve conditions directly related to COVID-19 (respiratory or viral infection) or conditions exacerbated by COVID-19 or other health care disruptions (diabetes or cardiovascular disease)5 but could not be discerned from the data.
June 27, 2022
The humoral response and antibodies against SARS-CoV-2 infection
Two and a half years into the COVID-19 pandemic, we have gained many insights into the human antibody response to the causative SARS-CoV-2 virus. In this Review, we summarize key observations of humoral immune responses in people with COVID-19, discuss key features of infection- and vaccine-induced neutralizing antibodies, and consider vaccine designs for inducing antibodies that are broadly protective against different variants of the SARS-CoV-2 virus.
Between Sept 30, 2021 and March 3, 2022, we recruited 340 participants, of whom 254 were included in the interim analysis and had been randomly assigned to one of the two groups: 127 in the continue methotrexate group and 127 in the suspend methotrexate group. Their mean age was 59·1 years, 155 (61%) were female, 130 (51%) had rheumatoid arthritis, and 86 (34%) had psoriasis with or without arthritis. After 4 weeks, the geometric mean S1-RBD antibody titre was 22 750 U/mL (95% CI 19 314–26 796) in the suspend methotrexate group and 10 798 U/mL (8970–12 997) in the continue methotrexate group, with a geometric mean ratio (GMR) of 2·19 (95% CI 1·57–3·04; p<0·0001; mixed-effects model). The increased antibody response in the suspend methotrexate group was consistent across methotrexate dose, administration route, type of immune-mediated inflammatory disease, age, primary vaccination platform, and history of SARS-CoV-2 infection. There were no intervention-related serious adverse events.
June 25, 2022
Naomi Oreskes: understanding the denial of science
Science denialism during the COVID-19 pandemic has been “a really serious problem”, Oreskes says. “I think we are noticing it because it is so present and so immediate—many of these other things have been on a kind of slow burn. There are people who died who didn’t have to die. And who, if they had been willing to follow scientific advice or if they had been encouraged to follow scientific advice, could be alive today…Trust in science has actually become a matter of life and death.” Yet she notes, “Overall trust in science as an activity…remains quite high…But that said, we have definite subsectors of the population who have rejected science in important areas with big consequences for public health.” She highlights how “The basic framework is the phenomenon of deliberate fomenting of distrust for political, ideological, and economic reasons. This is hugely important for scientists to understand. If we don’t actually understand, analyse, and work with these social factors, we won’t achieve the results that we want.”
June 24, 2022
This study found that individuals with mild COVID-19 infected during the Gamma and Omicron waves had lower odds of reporting olfactory dysfunction than individuals infected during the period of the original lineages. These results suggest that the type of SARS-CoV-2 variant might be a risk factor for olfactory dysfunction, along with host genetic susceptibility.2 The association with Omicron also was observed after controlling for vaccination status, supporting its independence of host immunologic factors.
The findings of this population-based cohort study of Ontario adolescents and adults with myocarditis or pericarditis following mRNA COVID-19 vaccination suggest that vaccine products and interdose intervals, in addition to age and sex, may be associated with the risk of myocarditis or pericarditis after receipt of these vaccines. Vaccination program strategies, such as age-based product considerations and longer interdose intervals, may reduce the risk of myocarditis or pericarditis following receipt of mRNA vaccines.
During October 1, 2021–June 15, 2022, a total of 296 U.S. pediatric patients received a diagnosis of hepatitis of unknown etiology, with adenovirus detected among 45%. Preliminary analyses have not identified common exposures (e.g., travel or toxicants).
June 23, 2022
Antigenic cartography of SARS-CoV-2 reveals that Omicron BA.1 and BA.2 are antigenically distinct
The emergence and rapid spread of SARS-CoV-2 variants may impact vaccine efficacy significantly. The Omicron variant termed BA.2, which differs substantially from BA.1 based on genetic sequence, is currently replacing BA.1 in several countries, but its antigenic characteristics have not yet been assessed. Here, we used antigenic cartography to quantify and visualize antigenic differences between early SARS-CoV-2 variants (614G, Alpha, Beta, Gamma, Zeta, Delta and Mu) using hamster antisera obtained after primary infection. We first verified that the choice of the cell line for the neutralization assay did not affect the topology of the map substantially. Antigenic maps generated using pseudotyped SARS-CoV-2 on the widely used VeroE6 cell line and the human airway cell line Calu-3 generated similar maps. Maps made using authentic SARS-CoV-2 on Calu-3 cells also closely resembled those generated with pseudotyped viruses. The antigenic maps revealed a central cluster of SARS-CoV-2 variants, which grouped based on mutual spike mutations. Whereas these early variants are antigenically similar, clustering relatively close to each other in antigenic space, Omicron BA.1 and BA.2 have evolved as two distinct antigenic outliers. Our data show that BA.1 and BA.2 both escape vaccine-induced antibody responses as a result of different antigenic characteristics. Thus, antigenic cartography could be used to assess antigenic properties of future SARS-CoV-2 variants of concern that emerge and to decide on the composition of novel spike-based (booster) vaccines.
Pathogenicity, transmissibility, and fitness of SARS-CoV-2 Omicron in Syrian hamsters
The in vivo pathogenicity, transmissibility, and fitness of the SARS-CoV-2 Omicron (B.1.1.529) variant are unclear. We compared these virological attributes of this new variant of concern with those of the Delta (B.1.617.2) variant in a Syrian hamster model of COVID-19. Omicron-infected hamsters lost significantly less body weight and exhibited reduced clinical scores, respiratory tract viral burdens, cytokine/chemokine dysregulation, and lung damage than Delta-infected hamsters. Both variants were highly transmissible via contact transmission. In non-contact transmission studies, Omicron demonstrated similar or higher transmissibility than Delta. Delta outcompeted Omicron without selection pressure. This scenario drastically changed once immune selection pressure with neutralizing antibodies active against Delta but poorly active against Omicron was introduced. Next-generation vaccines and antivirals effective against this new VOC are urgently needed.
Long-COVID in children and adolescents: a systematic review and meta-analyses
The objective of this systematic review and meta-analyses is to estimate the prevalence of long-COVID in children and adolescents and to present the full spectrum of symptoms present after acute COVID-19. We have used PubMed and Embase to identify observational studies published before February 10th, 2022 that included a minimum of 30 patients with ages ranging from 0 to 18 years that met the National Institute for Healthcare Excellence (NICE) definition of long-COVID, which consists of both ongoing (4 to 12 weeks) and post-COVID-19 (≥ 12 weeks) symptoms. Random-effects meta-analyses were performed using the MetaXL software to estimate the pooled prevalence with a 95% confidence interval (CI). Heterogeneity was assessed using I2 statistics. The Preferred Reporting Items for Systematic Reviewers and Meta-analysis (PRISMA) reporting guideline was followed (registration PROSPERO CRD42021275408). The literature search yielded 8373 publications, of which 21 studies met the inclusion criteria, and a total of 80,071 children and adolescents were included. The prevalence of long-COVID was 25.24%, and the most prevalent clinical manifestations were mood symptoms (16.50%), fatigue (9.66%), and sleep disorders (8.42%). Children infected by SARS-CoV-2 had a higher risk of persistent dyspnea, anosmia/ageusia, and/or fever compared to controls. Limitations of the studies analyzed include lack of standardized definitions, recall, selection, misclassification, nonresponse and/or loss of follow-up, and a high level of heterogeneity.
Global impact of the first year of COVID-19 vaccination: a mathematical modelling study
Based on official reported COVID-19 deaths, we estimated that vaccinations prevented 14·4 million (95% credible interval [Crl] 13·7–15·9) deaths from COVID-19 in 185 countries and territories between Dec 8, 2020, and Dec 8, 2021. This estimate rose to 19·8 million (95% Crl 19·1–20·4) deaths from COVID-19 averted when we used excess deaths as an estimate of the true extent of the pandemic, representing a global reduction of 63% in total deaths (19·8 million of 31·4 million) during the first year of COVID-19 vaccination. In COVAX Advance Market Commitment countries, we estimated that 41% of excess mortality (7·4 million [95% Crl 6·8–7·7] of 17·9 million deaths) was averted. In low-income countries, we estimated that an additional 45% (95% CrI 42–49) of deaths could have been averted had the 20% vaccination coverage target set by COVAX been met by each country, and that an additional 111% (105–118) of deaths could have been averted had the 40% target set by WHO been met by each country by the end of 2021.
SARS-CoV-2 spike protein, which forms the basis for high pathogenicity and transmissibility of the virus, is a prime target for the development of both diagnostics and vaccines for the debilitating disease caused by the virus. We present a full model of spike methodically crafted and used to study its atomic-level dynamics by multiple microsecond simulations. The results shed light on the impact of posttranslational modifications on the pathogenicity of the virus. We show how glycan–glycan and glycan–lipid interactions broaden the protein’s dynamical range and thereby, its effective interaction with the surface receptors on the host cell. Palmitoylation of the spike membrane domain, however, results in a unique deformation pattern that might prime the membrane for fusion.
June 22, 2022
Among 2 117 443 children included in the study, 253 children developed MIS-C, corresponding to an incidence rate of 6·8 (95% CI: 6·0-7·6) per 100 000 person-years. Male sex (HR 1·65, 95% CI: 1·28-2·14), age 5-11 years (adjusted HR 1·44, 95% CI: 1·06-1·95 using children 0-4 years as reference), foreign-born parents (HR 2·53, 95% CI: 1·93-3·34), asthma (aHR 1·49, 95% CI: 1·00-2·20), obesity (aHR 2·15, 95% CI: 1·09-4·25) and life-limiting conditions (aHR 3·10, 95% CI: 1·80-5·33) were associated with MIS-C. Children 16-18 years had a reduced risk for MIS-C (aHR 0·45, 95% CI: 0·24-0·85).
In this analysis of data from a mass COVID-19 vaccination site, the proportion of Black and Hispanic patients receiving the COVID-19 vaccine was substantially higher with CBO outreach than when self-scheduled through the patient portal. Restriction to local zip codes for self-scheduling was also associated with a higher proportion of racial and ethnic minority patients receiving the COVID-19 vaccine. These findings suggest that direct outreach from trusted community resources can address challenges navigating self-scheduling technology6 and may mitigate distrust of COVID-19 vaccination in Hispanic and Black communities.
COVID-19 mRNA Vaccine Booster During Pregnancy Increases Maternal and Fetal Antibodies
Pregnant individuals who received a booster dose of the BNT162b2 (Pfizer-BioNTech) COVID-19 mRNA vaccine during their second trimester developed higher antibody levels than those who received the second shot in their primary vaccine series during the same trimester, researchers in Israel recently reported in Obstetrics & Gynecology. Infants in the booster group also had higher antibody levels at birth than those in the 2-dose group. The study’s authors say the findings support a COVID-19 maternal booster following full COVID-19 vaccination to protect both pregnant people and their infants.
Maternal Vaccination and Risk of Hospitalization for Covid-19 among Infants
A total of 537 case infants (181 of whom had been admitted to a hospital during the delta period and 356 during the omicron period; median age, 2 months) and 512 control infants were enrolled and included in the analyses; 16% of the case infants and 29% of the control infants had been born to mothers who had been fully vaccinated against Covid-19 during pregnancy. Among the case infants, 113 (21%) received intensive care (64 [12%] received mechanical ventilation or vasoactive infusions). Two case infants died from Covid-19; neither infant’s mother had been vaccinated during pregnancy. The effectiveness of maternal vaccination against hospitalization for Covid-19 among infants was 52% (95% confidence interval [CI], 33 to 65) overall, 80% (95% CI, 60 to 90) during the delta period, and 38% (95% CI, 8 to 58) during the omicron period. Effectiveness was 69% (95% CI, 50 to 80) when maternal vaccination occurred after 20 weeks of pregnancy and 38% (95% CI, 3 to 60) during the first 20 weeks of pregnancy.
Covid-19 Vaccination during Pregnancy — Two for the Price of One
The benefits of maternal vaccination to the infant through maternal antibody transfer across the placenta have long been recognized. In the 1870s, babies born to mothers who had received smallpox vaccination were unlikely to have smallpox early in life.1 Tetanus toxoid vaccination during pregnancy, along with improved hygiene during delivery, has resulted in substantially reduced rates of neonatal tetanus in some developing countries.1 Decreased risks of influenza and pertussis have been reported during the first few months of life among infants whose mothers had received the inactivated influenza vaccine and the combined tetanus–diphtheria–acellular pertussis (Tdap) vaccine, respectively. Both vaccines are routinely recommended during pregnancy in the United States; the influenza vaccine is recommended anytime during pregnancy, whereas the Tdap vaccine is recommended preferentially during the early part of gestational weeks 27 to 36 in order to maximize maternal antibody production, placental transfer, and antibody levels in the newborn.2 Studies to evaluate whether maternal vaccination could prevent illness from other infections (e.g., respiratory syncytial virus infection or group B streptococcus infection) among infants are underway.
Evaluation of Acute Adverse Events after Covid-19 Vaccination during Pregnancy
Pregnant women with symptomatic coronavirus disease 2019 (Covid-19) have a higher risk of adverse outcomes than do women who are not pregnant.1,2 In part because of these findings, Covid-19 vaccination has been recommended for pregnant women. However, uptake has been lower in pregnant women than among women who are not pregnant.3,4 The concern of many women regarding safety remains a barrier to maternal vaccination.
Neutralization Escape by SARS-CoV-2 Omicron Subvariants BA.2.12.1, BA.4, and BA.5
In recent months, multiple lineages of the omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged,1 with subvariants BA.1 and BA.2 showing substantial escape from neutralizing antibodies.2-5 Subvariant BA.2.12.1 is now the dominant strain in the United States, and BA.4 and BA.5 are dominant in South Africa (Figure 1A). Subvariants BA.4 and BA.5 have identical sequences of the spike protein.
Compared with controls, children aged 0–14 years who had a SARS-CoV-2 infection had more prevalent long-lasting symptoms. There was a tendency towards better quality-of-life scores related to emotional and social functioning in cases than in controls in older children. The burden of symptoms among children in the control group requires attention. Long COVID must be recognised and multi-disciplinary long COVID clinics for children might be beneficial.
June 21, 2022
During December 23, 2021–May 21, 2022, 1,076,762 oral antiviral prescriptions were dispensed in the United States. The overall number of antivirals dispensed increased; however, by the end of the study period, dispensing rates were lowest in high vulnerability zip codes, despite these zip codes having the largest number of dispensing sites.
COVID-19–related hospital admissions and emergency department (ED) encounters occurring 5–15 days after Paxlovid treatment were described using data from a large integrated health care system. Reports of such hospitalizations or ED encounters occurred infrequently, representing <1% of Paxlovid-treated patients over the study period.
Baricitinib Is First Approved COVID-19 Immunomodulatory Treatment
Baricitinib (Olumiant) recently became the first immunomodulatory treatment for COVID-19 to receive FDA approval. The agency approved it for treating COVID-19 among hospitalized adults requiring supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Baricitinib, discovered by Incyte and licensed to Eli Lilly, still remains under Emergency Use Authorization (EUA) status for hospitalized patients aged 2 years through 17 years who require breathing help.
mRNA COVID-19 Vaccine Booster After Inactivated Vaccine Primary Series
A booster shot of mRNA vaccine after 2 doses of inactivated virus vaccine significantly increases immune response to the SARS-CoV-2 virus, and may offer better protection against severe COVID-19 than 3 doses of inactivated vaccine, suggests a preliminary study published in Nature Communications.
A total of 1.5 million hours of physiological data were recorded from 1163 participants (mean age 44±5.5 years). COVID-19 was confirmed in 127 participants of which, 66 (52%) had worn their device from baseline to symptom onset (SO) and were included in this analysis. Multi-level modelling revealed significant changes in five (RR, HR, HRV, HRV ratio and WST) device-measured physiological parameters during the incubation, presymptomatic, symptomatic and recovery periods of COVID-19 compared with baseline. The training set represented an 8-day long instance extracted from day 10 to day 2 before SO. The training set consisted of 40 days measurements from 66 participants. Based on a random split, the test set included 30% of participants and 70% were selected for the training set. The developed long short-term memory (LSTM) based recurrent neural network (RNN) algorithm had a recall (sensitivity) of 0.73 in the training set and 0.68 in the testing set when detecting COVID-19 up to 2 days prior to SO.
Respiratory droplets are widely recognized as the primary vehicle in viral respiratory disease transmission. Accurate information on their number and size distributions is important for appropriate mitigation strategies, for quantitative modeling of airborne disease transmission, and for evaluating the relative importance of droplets originating from saliva versus airway lining fluid. A straightforward experimental setup using inexpensive, readily available components is developed for simultaneous characterization of larger particles by video analysis of laser light scattering and monitoring of smaller sizes by an optical particle counter. Measurements indicate that in a healthy volunteer, the airborne mass of speech aerosol far exceeds that generated by breathing, even when accounting for faster sedimentation of the larger particles.
The results were consistent in comparisons versus the historical and vaccinated controls. Compared to people with SARS-CoV-2 infection who were not previously vaccinated (n = 113,474), people with BTI exhibited lower risks of death (HR = 0.66, 95% CI: 0.58, 0.74) and incident post-acute sequelae (HR = 0.85, 95% CI: 0.82, 0.89). Altogether, the findings suggest that vaccination before infection confers only partial protection in the post-acute phase of the disease; hence, reliance on it as a sole mitigation strategy may not optimally reduce long-term health consequences of SARS-CoV-2 infection. The findings emphasize the need for continued optimization of strategies for primary prevention of BTI and will guide development of post-acute care pathways for people with BTI.
Although substantial federal funding has been available to improve indoor ventilation and filtration in schools to slow the spread of SARS-CoV-2, most US public schools have made no major investments in such strategies since the emergence of the COVID-19 pandemic, according to a study from the Centers for Disease Control and Prevention (CDC).
Experimental Open-source Low-cost Ventilator Could Meet Critical Need
An experimental device that meets US Food and Drug Administration (FDA) performance requirements for emergency use ventilators can be constructed for about $1700—far less than the $10 000 for the lowest-cost commercial models, according to an article in PLoS One.
June 20, 2022
Drivers of adaptive evolution during chronic SARS-CoV-2 infections
In some immunocompromised patients with chronic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, considerable adaptive evolution occurs. Some substitutions found in chronic infections are lineage-defining mutations in variants of concern (VOCs), which has led to the hypothesis that VOCs emerged from chronic infections. In this study, we searched for drivers of VOC-like emergence by consolidating sequencing results from a set of 27 chronic infections. Most substitutions in this set reflected lineage-defining VOC mutations; however, a subset of mutations associated with successful global transmission was absent from chronic infections. We further tested the ability to associate antibody evasion mutations with patient-specific and virus-specific features and found that viral rebound is strongly correlated with the emergence of antibody evasion. We found evidence for dynamic polymorphic viral populations in most patients, suggesting that a compromised immune system selects for antibody evasion in particular niches in a patient’s body. We suggest that a tradeoff exists between antibody evasion and transmissibility and that extensive monitoring of chronic infections is necessary to further understanding of VOC emergence.
Here we developed three recombinant Newcastle disease virus (rNDV) vectored vaccines and assessed their immunogenicity, safety, and protective efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in mice and hamsters. Intranasal administration of rNDV-based vaccine candidates elicited high levels of neutralizing antibodies. Importantly, the nasally administrated vaccine prevented lung damage, and significantly reduced viral load in the respiratory tract of vaccinated animal which was compounded by profound humoral immune responses. Taken together, the presented NDV-based vaccine candidates fully protected animals against SARS-CoV-2 challenge and warrants evaluation in a Phase I human clinical trial as a promising tool in the fight against COVID-19.
June 19, 2022
Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant
The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron, although the boosted titers decline rapidly within 2 months from the peak response compared with boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared with homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared with BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2.
June 18, 2022
Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2
Overall, we found a reduction in odds of long COVID with the omicron variant versus the delta variant of 0·24–0·50 depending on age and time since vaccination. However, the absolute number of people experiencing long COVID at a given time depends on the shape and amplitude of the pandemic curve. For example, given the high numbers of people infected with omicron in the UK from December, 2021, to February, 2022, our data are consistent with the UK Office for National Statistics, who estimated that the numbers of people experiencing long COVID actually increased from 1·3 million in January, 2022, to 1·7 million in March, 2022. Considering the UK omicron peak of more than 350 000 new symptomatic COVID-19 cases per day estimated on March 26, 2022, by the ZOE app model and 4% of cases being long COVID, future numbers with long COVID will inevitably rise.
June 17, 2022
A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants
A comprehensive understanding of host dependency factors for SARS-CoV-2 remains elusive. Here, we map alterations in host lipids following SARS-CoV-2 infection using nontargeted lipidomics. We find that SARS-CoV-2 rewires host lipid metabolism, significantly altering hundreds of lipid species to effectively establish infection. We correlate these changes with viral protein activity by transfecting human cells with each viral protein and performing lipidomics. We find that lipid droplet plasticity is a key feature of infection and that viral propagation can be blocked by small-molecule glycerolipid biosynthesis inhibitors. We find that this inhibition was effective against the main variants of concern (alpha, beta, gamma, and delta), indicating that glycerolipid biosynthesis is a conserved host dependency factor that supports this evolving virus.
BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection
SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility over BA.21. The new variants’ receptor binding and immune evasion capability require immediate investigation. Here, coupled with Spike structural comparisons, we show that BA.2.12.1 and BA.4/BA.5 exhibit comparable ACE2-binding affinities to BA.2. Importantly, BA.2.12.1 and BA.4/BA.5 display stronger neutralization evasion than BA.2 against the plasma from 3-dose vaccination and, most strikingly, from post-vaccination BA.1 infections. To delineate the underlying antibody evasion mechanism, we determined the escaping mutation profiles2, epitope distribution3 and Omicron neutralization efficacy of 1640 RBD-directed neutralizing antibodies (NAbs), including 614 isolated from BA.1 convalescents. Interestingly, post-vaccination BA.1 infection mainly recalls wildtype-induced humoral memory. The resulting elicited antibodies could neutralize both wildtype and BA.1 and are enriched on non-ACE2-competing epitopes. However, most of these cross-reactive NAbs are heavily escaped by L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1; nevertheless, these NAbs are largely escaped by BA.2/BA.4/BA.5 due to D405N and F486V, and react weakly to pre-Omicron variants, exhibiting poor neutralization breadths. As for therapeutic NAbs, Bebtelovimab4 and Cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, while the S371F, D405N and R408S mutations would undermine most broad sarbecovirus NAbs. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.
COVID-19–associated hospitalization rates among disability-eligible Medicare beneficiaries (3,148 per 100,000) were approximately 50% higher than rates among age-eligible (i.e., ≥65 years) beneficiaries (2,129 per 100,000), and hospitalization rates increased by age in both groups. Among persons with disabilities, American Indian or Alaska Native persons experienced the highest rate of COVID-19–associated hospitalization (4,962 per 100,000).
U.S. adults aged ≥65 years are at increased risk for severe illness and death from COVID-19 (1). The communal nature of long-term care facilities (LTCFs), and the vulnerability of the LTCF population (typically aged ≥65 years, and often having underlying chronic conditions, cognitive and physical impairments, immunocomprised status, or other disabilities) further increases risk for COVID-19 infection, hospitalization, and death in this group (2). Although multiple studies highlight these risks (3), there is limited information comparing the risk among LTCF residents with that in an age-comparable population living in the community. This report estimates the risk for death among LTCF residents by comparing COVID-19–associated mortality rates among LTCF residents aged ≥65 years and persons aged ≥65 years who are not LTCF residents (community-dwelling adults) in Illinois. Illinois infectious disease registry data and population data from state regulatory sources and the U.S. Census Bureau were used to calculate COVID-19 death rates among persons aged ≥65 years living within and outside of LTCFs during a prevaccination baseline month (December 2020) and a comparison month 1 year after COVID-19 vaccination began (January 2022).
This randomized clinical trial among 8287 Black and Latino adults aged 65 years and older found that both standard and culturally tailored electronic secure messages and mailings from individuals’ own PCPs led to significantly higher COVID-19 vaccination rates at 8 weeks than usual care. There was no difference in vaccination rates between standard and culturally tailored PCP outreach.
Perspectives of Latinx Individuals Who Were Unvaccinated And Hospitalized for COVID-19
In this qualitative study consisting of interviews with 25 Latinx individuals who were unvaccinated and hospitalized with COVID-19, participants described the impact of hospitalization on their vaccine deliberation. After hospitalization, Latinx individuals who remained undecided and those who ultimately accepted the COVID-19 vaccine described COVID-19 vaccine concerns, and those who were vaccinated after hospitalization were motivated to engage in advocacy to encourage vaccination and suggested additional patient-centered opportunities to increase vaccine uptake.
In this cohort study of 3922 children with KD, cases of KD across the United States fell by 28% and remained low during periods of COVID-19–related masking and school closure. In the San Diego region, there was a disproportionate decline in KD cases in children aged 1 to 5 years, male children, and Asian children, and clinical features including strawberry tongue, enlarged cervical lymph node, and subacute periungual desquamation were rare.
Outcomes of SARS-CoV-2 Reinfection
First infection with SARS-CoV-2 is associated with increased risk of acute and post-acute death and sequelae in the pulmonary and extrapulmonary organ systems. However, whether reinfection adds to the risk incurred after the first infection is not clear. Here we use the national health care databases of the US Department of Veterans Affairs to build a cohort of people with first infection (n = 257,427), reinfection (2 or more infections, n = 38,926), and a non-infected control group (n = 5,396,855) to estimate risks and 6-month burdens of all-cause mortality, hospitalization, and a set of pre-specified incident outcomes. We show that compared to people with first infection, reinfection contributes additional risks of all-cause mortality, hospitalization, and adverse health outcomes in the pulmonary and several extrapulmonary organ systems (cardiovascular disorders, coagulation and hematologic disorders, diabetes, fatigue, gastrointestinal disorders, kidney disorders, mental health disorders, musculoskeletal disorders, and neurologic disorders); the risks were evident in those who were unvaccinated, had 1 shot, or 2 or more shots prior to the second infection; the risks were most pronounced in the acute phase, but persisted in the post-acute phase of reinfection, and most were still evident at 6 months after reinfection. Compared to non-infected controls, assessment of the cumulative risks of repeated infection showed that the risk and burden increased in a graded fashion according to the number of infections. The constellation of findings show that reinfection adds non-trivial risks of all-cause mortality, hospitalization, and adverse health outcomes in the acute and post-acute phase of the reinfection. Reducing overall burden of death and disease due to SARS-CoV-2 will require strategies for reinfection prevention.
June 16, 2022
Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae
The diagnosis and management of post-acute sequelae of COVID-19 (PASC) poses an ongoing medical challenge. Identifying biomarkers associated with PASC would immensely improve the classification of PASC patients and provide the means to evaluate treatment strategies. We analyzed plasma samples collected from a cohort of PASC and COVID-19 patients (n = 63) to quantify circulating viral antigens and inflammatory markers. Strikingly, we detect SARS-CoV-2 spike antigen in a majority of PASC patients up to 12 months post-diagnosis, suggesting the presence of an active persistent SARS-CoV-2 viral reservoir. Furthermore, temporal antigen profiles for many patients show the presence of spike at multiple time points over several months, highlighting the potential utility of the SARS-CoV-2 full spike protein as a biomarker for PASC.
Timely evaluation of the protective effects of Coronavirus Disease 2019 (COVID-19) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern is urgently needed to inform pandemic control planning. Based on 78 vaccine efficacy or effectiveness (VE) data from 49 studies and 1,984,241 SARS-CoV-2 sequences collected from 31 regions, we analyzed the relationship between genetic distance (GD) of circulating viruses against the vaccine strain and VE against symptomatic infection. We found that the GD of the receptor-binding domain of the SARS-CoV-2 spike protein is highly predictive of vaccine protection and accounted for 86.3% (P = 0.038) of the VE change in a vaccine platform-based mixed-effects model and 87.9% (P = 0.006) in a manufacturer-based model. We applied the VE-GD model to predict protection mediated by existing vaccines against new genetic variants and validated the results by published real-world and clinical trial data, finding high concordance of predicted VE with observed VE. We estimated the VE against the Delta variant to be 82.8% (95% prediction interval: 68.7–96.0) using the mRNA vaccine platform, closely matching the reported VE of 83.0% from an observational study. Among the four sublineages of Omicron, the predicted VE varied between 11.9% and 33.3%, with the highest VE predicted against BA.1 and the lowest against BA.2, using the mRNA vaccine platform. The VE-GD framework enables predictions of vaccine protection in real time and offers a rapid evaluation method against novel variants that may inform vaccine deployment and public health responses.
They span three continents, but a trio of researchers who’ve never met share a singular focus made vital by the still-raging pandemic: deciphering the causes of Long Covid and figuring out how to treat it.
Effectiveness of a COVID-19 Testing Outreach Intervention for Latinx Communities
In this cluster randomized trial of 33 SARS-CoV-2 testing sites, the community health promoters intervention was associated with 3.84 times more Latinx individuals tested per event than control sites, and the intervention was associated with testing a greater proportion of the Latinx populace per event.
Association of COVID-19 Stay-at-Home Orders With 1-Year Weight Changes
Participants had statistically significant increases in weight during the preshutdown year (mean change, 0.18 [95% CI, 0.15 to 0.22] kg) and postshutdown year (mean change, 0.22 [95% CI, 0.19 to 0.26] kg), but the difference between the preshutdown and postshutdown changes was not significant (difference, 0.04 [95% CI, −0.01 to 0.10] kg; P = .11) (Table). The sensitivity analysis including only patients with all 4 measures assessed in-person found significantly less weight gain in the postshutdown interval vs preshutdown interval (Table). The percentage of individuals who remained weight-stable decreased by 2% from the preshutdown to postshutdown periods, whereas the percentage who either gained or lost 5% increased by approximately 0.7% (Figure). Changes in weight from preshutdown to postshutdown periods did not differ among subgroups. Results for BMI were similar (Table).
BBV152 was well tolerated in children aged 2–18 years, and induced higher neutralising antibody responses than those observed in adults, in whom the efficacy (ie, the prevention or decrease in the severity of COVID-19 infection) has been demonstrated.
June 15, 2022
How months-long COVID infections could seed dangerous new variants
Tracking SARS-CoV-2 evolution during persistent cases provides insight into the origins of Omicron and other global variants. What can scientists do with this knowledge?
In this survey study of more than 1.4 million respondents in the US Behavioral Risk Factor Surveillance System survey, responses to a screening question calibrated to a 4-item Patient Health Questionnaire score of 6 or greater suggested that aggregate prevalence of clinically significant anxiety and depression increased only modestly overall among US adults in 2020 compared with 2017 to 2019.
There were 295 771 patients admitted for 1 825 610 hospital-days (mean, 6.2 days per admission); 13 392 admissions included a diagnosis of SARS-CoV-2 infection (53.3% men; mean age, 61.3 years) and 434 cases (3.2%) were diagnosed on hospital day 5 or later. Of these, 178/3820 (4.7%) were diagnosed during the 2021-2022 Omicron winter surge and 111/3218 (3.4%) during the 2020-2021 winter surge (Table). The incidence of hospital-onset infections was significantly higher during the winter 2021-2022 Omicron surge vs the prior winter surge: 0.87 vs 0.56 cases per 1000 patient-days for diagnoses on hospital day 5 or later (relative risk [RR], 1.54; 95% CI, 1.22-1.95), 0.57 vs 0.35 for diagnoses on hospital day 8 or later (RR, 1.62; 95% CI, 1.21-2.18), and 0.37 vs 0.16 for diagnoses on hospital day 15 or later (RR, 2.31; 95% CI, 1.53-3.49). The increase in hospital-onset infections during the Omicron wave vs the prior winter wave mirrored similar increases in community and health care worker case numbers during these same periods (Figure).
As the US reckons with the consequences of the COVID-19 pandemic, there has been growing discussion of the ways in which unmet social needs can be met within health care systems. Adding to this conversation, organizational leaders and clinicians in health care systems are uniquely positioned to contribute to changes in broader social systems outside their walls. Specifically, safety net programs and other social policies serve as powerful population-level interventions that can affect long-standing health disparities. For example, the largest US poverty alleviation program—the Earned Income Tax Credit—is associated with improved birth outcomes, and more so for Black women who have the highest rates of preterm birth due in part to toxic exposures to structural racism. Academic and nonacademic health care systems have an important role in generating the science, case examples, and momentum toward strengthening social safety net programs to the end of narrowing health gaps.
June 14, 2022
Following identification of pediatric hepatitis cases of unknown etiology in the United States and the United Kingdom, CDC issued a request in April 2022 for U.S. providers to report additional cases. Many reported cases had test results positive for adenovirus, which is not known to cause hepatitis in immunocompetent children.
Among immunocompetent patients, VE against Omicron COVID-19 hospitalization for a primary series plus one booster of any vaccine product dose was 77% (95% CI: 71-82%), and for a primary series alone was 44% (95% CI: 31-54%) (p<0.001). VE was higher for a boosted regimen than a primary series alone for both mRNA vaccines used in the US (BNT162b2: primary series plus booster VE 80% (95% CI: 73-85%), primary series alone VE 46% (95% CI: 30-58%) [p<0.001]; mRNA-1273: primary series plus booster VE 77% (95% CI: 67-83%), primary series alone VE 47% (95% CI: 30-60%) [p<0.001]). Among immunocompromised patients, VE for a primary series of any vaccine product against Omicron COVID-19 hospitalization was 60% (95% CI: 41-73%). Insufficient sample size has accumulated to calculate effectiveness of boosted regimens for immunocompromised patients. Conclusions: Among immunocompetent people, a booster dose of COVID-19 vaccine provided additional benefit beyond a primary vaccine series alone for preventing COVID-19 hospitalization due to the Omicron variant.
Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure
The Omicron, or Pango lineage B.1.1.529, variant of SARS-CoV-2 carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection from severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple mRNA vaccinated healthcare workers (HCW) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple vaccinated individuals, but magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCW who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants, but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529.
June 13, 2022
Rapid, scalable assessment of SARS-CoV-2 cellular immunity by whole-blood PCR
Fast, high-throughput methods for measuring the level and duration of protective immune responses to SARS-CoV-2 are needed to anticipate the risk of breakthrough infections. Here we report the development of two quantitative PCR assays for SARS-CoV-2-specific T cell activation. The assays are rapid, internally normalized and probe-based: qTACT requires RNA extraction and dqTACT avoids sample preparation steps. Both assays rely on the quantification of CXCL10 messenger RNA, a chemokine whose expression is strongly correlated with activation of antigen-specific T cells. On restimulation of whole-blood cells with SARS-CoV-2 viral antigens, viral-specific T cells secrete IFN-γ, which stimulates monocytes to produce CXCL10. CXCL10 mRNA can thus serve as a proxy to quantify cellular immunity. Our assays may allow large-scale monitoring of the magnitude and duration of functional T cell immunity to SARS-CoV-2, thus helping to prioritize revaccination strategies in vulnerable populations.
The fragmented and inefficient healthcare system in the United States leads to many preventable deaths and unnecessary costs every year. Universal healthcare could have alleviated the mortality caused by a confluence of negative COVID-related factors. Incorporating the demography of the uninsured with age-specific COVID-19 and nonpandemic mortality, we estimated that a single-payer universal healthcare system would have saved 212,000 lives in 2020 alone. We also calculated that US$105.6 billion of medical expenses associated with COVID-19 hospitalization could have been averted by a Medicare for All system.
New COVID drugs face delays as trials grow more difficult
Fewer people are eligible for the massive studies needed to test treatments for severe COVID-19.
Effect of Text Messaging and Behavioral Interventions on COVID-19 Vaccination Uptake
In this randomized clinical trial comprising 16 045 participants, text messaging did not result in a higher response rate than outbound telephone calls. Behaviorally informed messaging did not result in a significantly higher response than usual content.
June 12, 2022
Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation
COVID survivors frequently experience lingering neurological symptoms that resemble cancer therapy-related cognitive impairment, a syndrome for which white-matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared to SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis and elevated CCL11 at early timepoints, but after influenza only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.
June 11, 2022
A total of 411 myocarditis or pericarditis, or both, events were observed among 15 148 369 people aged 18–64 years who received 16 912 716 doses of BNT162b2 and 10 631 554 doses of mRNA-1273. Among men aged 18–25 years, the pooled incidence rate was highest after the second dose, at 1·71 (95% CI 1·31 to 2·23) per 100 000 person-days for BNT162b2 and 2·17 (1·55 to 3·04) per 100 000 person-days for mRNA-1273. The pooled IRR in the head-to-head comparison of the two mRNA vaccines was 1·43 (95% CI 0·88 to 2·34), with an excess risk of 27·80 per million doses (–21·88 to 77·48) in mRNA-1273 recipients compared with BNT162b2.
June 10, 2022
Asian and non-Hispanic White adults had the highest COVID-19 vaccination coverage by the end of April 2021. By the end of November 2021, disparities in vaccination coverage for some racial and ethnic groups narrowed, and coverage was similar for non-Hispanic Black (78.2%), Hispanic (81.3%), Native Hawaiian and other Pacific Islander (75.7%), and non-Hispanic White (78.7%) adults.
A recent outbreak of acute non-A-E hepatitis with serum transaminases greater than 500 IU/L identified in children aged under 16 years reported in United Kingdom (UK) has become a serious cause for concern for public health authorities and paediatric liver and critical care services. From 1 January to 16 May 2022, UK public health authorities have reported 197 cases with median age 3 years, male (50%), from all regions of UK with 11 children requiring liver transplantation (LT).
June 9, 2022
Despite the ability of current vaccines to significantly prevent severe disease due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), vaccinated individuals are still susceptible to infection and contribute to the spread of the virus. The present study demonstrates that a live, replication-deficient recombinant virus vaccine induces greater immunity and a greater level of protection in the respiratory tract of susceptible transgenic mice when inoculated intranasally compared with intramuscularly. Second-generation vaccines administered via the upper respiratory tract have the potential to limit the spread of SARS-CoV-2 more effectively than current vaccines.
Intramuscular AZD7442 (Tixagevimab–Cilgavimab) for Prevention of Covid-19
A total of 5197 participants underwent randomization and received one dose of AZD7442 or placebo (3460 in the AZD7442 group and 1737 in the placebo group). The primary analysis was conducted after 30% of the participants had become aware of their randomized assignment. In total, 1221 of 3461 participants (35.3%) in the AZD7442 group and 593 of 1736 participants (34.2%) in the placebo group reported having at least one adverse event, most of which were mild or moderate in severity. Symptomatic Covid-19 occurred in 8 of 3441 participants (0.2%) in the AZD7442 group and in 17 of 1731 participants (1.0%) in the placebo group (relative risk reduction, 76.7%; 95% confidence interval [CI], 46.0 to 90.0; P<0.001); extended follow-up at a median of 6 months showed a relative risk reduction of 82.8% (95% CI, 65.8 to 91.4). Five cases of severe or critical Covid-19 and two Covid-19–related deaths occurred, all in the placebo group.
Protection and Waning of Natural and Hybrid Immunity to SARS-CoV-2
The number of cases of SARS-CoV-2 infection per 100,000 person-days at risk (adjusted rate) increased with the time that had elapsed since vaccination with BNT162b2 or since previous infection. Among unvaccinated persons who had recovered from infection, this rate increased from 10.5 among those who had been infected 4 to less than 6 months previously to 30.2 among those who had been infected 1 year or more previously. Among persons who had received a single dose of vaccine after previous infection, the adjusted rate was low (3.7) among those who had been vaccinated less than 2 months previously but increased to 11.6 among those who had been vaccinated at least 6 months previously. Among previously uninfected persons who had received two doses of vaccine, the adjusted rate increased from 21.1 among those who had been vaccinated less than 2 months previously to 88.9 among those who had been vaccinated at least 6 months previously.
Monoclonal Antibodies with Extended Half-Life to Prevent Covid-19
Continued evolution of the spike protein is the biggest threat to all monoclonal antibody–based interventions against SARS-CoV-2, and it can be stymied only by decreasing the total global burden of viral replication in human hosts. Although the shifting antigenic landscape of the spike protein may mean that monoclonal antibodies will require periodic updates, the ability to passively immunize persons who have an increased risk of an ineffective immune response is an important leap forward in the ongoing fight against viral evolution.
Effectiveness of Ad26.COV2.S and BNT162b2 Vaccines against Omicron Variant in South Africa
After two doses, both vaccines were equally effective against severe disease caused by the omicron variant. These estimates of vaccine effectiveness were calculated in a South African population with a high background prevalence of SARS-CoV-2 exposure during the Covid-19 pandemic.5 These data provide reassurance about the continued value of the national Covid-19 vaccine program during a surge in the omicron variant.
There were no differences in spike-specific T-cell responses between participants 7 weeks after omicron breakthrough infection and participants without omicron infection, regardless of previous SARS-CoV-2 infection status (figure B,D). A significant increase in specific T-cells against nucleocapsid and membrane proteins was observed in omicron-infected individuals without past SARS-CoV-2 infection, showing that omicron breakthrough infection can prime specific T-cells (appendix p 11). Higher serological responses against both BA.1 and BA.2, but similar T-cell responses, were observed in BA.1-infected compared with BA.2-infected individuals (appendix p 12).
From April 9, 2021, to April 17, 2021, 663 COVID-19 convalescent participants were enrolled in the study; 213 participants did not meet the selection criteria and 450 volunteers were recruited. 20 participants aged 60–78 years were included in the open, single-group, phase 2a study and 430 participants were randomly assigned to the experimental (n=344) or control groups (n=86) in the phase 2b study of participants aged 19–78 years. 19 (95%) of 20 phase 2a volunteers achieved a successful immune response after vaccination. No vaccine-associated serious adverse events were reported in the whole study population. Minor adverse events were found, the most common being pain at the injection site (105 [29%] of 364 in the intervention group; 13 [15%] of 86 in the placebo group). A successful immune response was found in 289 (81%) of 358 participants 28 days after vaccination. The vaccine elicited a greater than 31-times increase in anti-RBD-IgG antibodies compared with prevaccination rates, and the seroconversion rate was 302 (84%) of 358 on day 28 after vaccination; the geometric mean titres of live-virus neutralisation test increased from 15·4 (95% CI 10·3–23·2) to 400·3 (272·4–588·1) and high response was found against alpha, beta, and delta variants of concern.
June 8, 2022
SARS-CoV-2 Evolution and Immune Escape in Immunocompromised Patients
Our results underscore the potential importance of selective pressures such as the use of monoclonal antibodies — in combination with the lack of an effective endogenous immune response — in promoting the emergence of SARS-CoV-2 escape mutations. These findings highlight the need to better understand the ramifications of different therapies in immunocompromised patients. Our results also corroborate the findings of previous studies in which patients with B-cell deficiencies were found to elicit effector T cells,5 an outcome that may signal an important role for T cells in controlling infection.
Protection Due to Previous SARS-CoV-2 Infection
The implication is that the phenomenon of enhanced vaccine response would be less effective if the infection involved a heterologous spike protein from a variant of concern than if the infection involved a spike protein that was homologous with the spike protein expressed by the vaccine. Arguably, there might even be a hierarchy of immune responses, depending on the heterologous infection subtype. Insights to be gained from research about the relation between protective efficacy and variant subtype in a previous infection may also inform the formulation of future vaccines.
From Positive t o Negative to Positive Again—The Mystery of Why COVID-19 Rebounds in Some Patients Who Take Paxlovid
Ho dismisses Pfizer’s contention that rebound is uncommon. He and his coauthors noted that 5 of the 10 relapses described in their report occurred within 2 families—2 in his family and 3 in another—suggesting it isn’t rare. That’s concerning, Ho said, because it appears that people who experience a relapse can infect others. Among the 10 cases in the report he coauthored, viral load during the relapse was comparable to levels during the initial infection. During their relapse, 1 symptomatic and 1 presymptomatic patient transmitted SARS-CoV-2 to family members, Ho and his coauthors wrote.
Epidemiologic surveillance has revealed decoupling of COVID-19 hospitalizations and deaths from case counts following emergence of the Omicron (B.1.1.529) SARS-CoV-2 variant globally. However, assessment of the relative severity of Omicron variant infections presents challenges because of differential acquired immune protection against Omicron and prior variants, and because longer-term changes have occurred in testing and healthcare practices. Here we show that Omicron variant infections were associated with substantially reduced risk of progression to severe clinical outcomes relative to time-matched Delta (B.1.617.2) variant infections within a large, integrated healthcare system in southern California. Adjusted hazard ratios (aHRs) for any hospital admission, symptomatic hospital admission, intensive care unit admission, mechanical ventilation, and death comparing cases with Omicron versus Delta variant infection were 0.59 (95% confidence interval: 0.51-0.69), 0.59 (0.51-0.68), 0.50 (0.29-0.87), 0.36 (0.18-0.72), and 0.21 (0.10-0.44) respectively. This reduced severity could not be explained by differential history of prior infection among cases with Omicron or Delta variant infection, and was starkest among cases not previously vaccinated against COVID-19 (aHR=0.40 [0.33-0.49] for any hospital admission and 0.14 [0.07-0.28] for death). Infections with the Omicron BA.2 subvariant were not associated with differential risk of severe outcomes in comparison to BA.1/BA.1.1 subvariant infections. Lower risk of severe clinical outcomes among cases with Omicron variant infection should inform public health response amid establishment of the Omicron variant as the dominant SARS-CoV-2 lineage globally.
Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1.
Neutralisation sensitivity of SARS-CoV-2 omicron subvariants to therapeutic monoclonal antibodies
During the current pandemic, SARS-CoV-2 has considerably diversified. The omicron variant (B.1.1.529) was identified at the end of November, 2021, and rapidly spread worldwide. As of May, 2022, the omicron BA.2 subvariant is the most dominant variant in the world. Other omicron subvariants have since emerged and some of them have begun to outcompete BA.2 in multiple countries. For instance, omicron BA.2.11 subvariant is spreading in France, and the BA.2.12.1 and BA.4/5 subvariants are becoming dominant in the USA and South Africa, respectively.
SARS-CoV-2 Evolution and Immune Escape in Immunocompromised Patients
Mutations in the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that confer escape from neutralizing antibodies can arise in immunocompromised patients with prolonged infection. Such viral evasion is hypothesized to contribute to the emergence of global variants of concern. In the absence of effective immune responses, selective pressures such as those from monoclonal antibody treatment may lead to the emergence of immunologically important mutations.
Mutations matter even if proteins stay the same
Although some mutations in a gene alter the amino-acid sequence of the protein that the gene encodes, others — known as synonymous mutations — have no effect on protein sequence. Does it follow, then, that synonymous mutations are unimportant? Writing in Nature, Shen et al.1 present evidence that synonymous mutations are frequently just as harmful as the non-synonymous mutations that alter proteins, upending a common assumption about molecular evolution.
In this cohort study, SARS-CoV-2 genome sequences in air samples collected at a nurses station were identified in all particle sizes and were identical to human samples from a nosocomial outbreak. Detection of aerosol-borne SARS-CoV-2 was statistically less frequent on units under surveillance (7 of 210 samples) than without surveillance (24 of 300 samples).
Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum
The Omicron lineage of SARS-CoV-2, first described in November 2021, spread rapidly to become globally dominant and has split into a number of sub-lineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africa’s Gauteng region uncovered two new sub-lineages, BA.4 and BA.5 which are taking over locally, driving a new wave. BA.4 and BA.5 contain identical spike sequences and, although closely related to BA.2, contain further mutations in the receptor binding domain of spike. Here, we study the neutralization of BA.4/5 using a range of vaccine and naturally immune serum and panels of monoclonal antibodies. BA.4/5 shows reduced neutralization by serum from triple AstraZeneca or Pfizer vaccinated individuals compared to BA.1 and BA.2. Furthermore, using serum from BA.1 vaccine breakthrough infections there are likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections.
June 7, 2022
Effect of Molnupiravir on Biomarkers, Respiratory Interventions, and Medical Services in COVID-19
Participants receiving molnupiravir showed faster normalization of CRP and Spo2, with improvements observed on day 3 of therapy, compared with placebo. Molnupiravir-treated participants had a decreased need for respiratory interventions versus placebo-treated participants (relative risk reduction [RRR], 34.3% [95% CI, 4.3% to 54.9%]), with similar findings in participants who were hospitalized after randomization (RRR, 21.3% [CI, 0.2% to 38.0%]). Hospitalized participants who received molnupiravir were discharged a median of 3 days before those who received placebo. Acute care visits (7.2% vs. 10.6%; RRR, 32.1% [CI, 4.4% to 51.7%]) and COVID-19–related acute care visits (6.6% vs. 10.0%; RRR, 33.8% [CI, 5.6% to 53.6%]) were less frequent in molnupiravir- versus placebo-treated participants.
Among a nationally representative sample of U.S. K–12 public schools, higher-cost and resource-intensive ventilation improvement strategies, such as using portable high-efficiency particular air (HEPA) filtration systems in classrooms were less frequently reported. Overall, rural and mid-poverty schools were the least likely to report implementing several resource-intensive ventilation strategies.
The host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in prolonged pathologies collectively referred to as post-acute sequalae of COVID-19 (PASC) or long COVID. To better understand the mechanism underlying long COVID biology, we compared the short- and long-term systemic responses in the golden hamster following either SARS-CoV-2 or influenza A virus (IAV) infection. Results demonstrated that SARS-CoV-2 exceeded IAV in its capacity to cause permanent injury to the lung and kidney and uniquely impacted the olfactory bulb (OB) and epithelium (OE). Despite a lack of detectable infectious virus, the OB and OE demonstrated myeloid and T cell activation, proinflammatory cytokine production, and an interferon response that correlated with behavioral changes extending a month post viral clearance. These sustained transcriptional changes could also be corroborated from tissue isolated from individuals who recovered from COVID-19. These data highlight a molecular mechanism for persistent COVID-19 symptomology and provide a small animal model to explore future therapeutics.
Reducing SARS-CoV-2 in Shared Indoor Air
Improving air quality has the potential to reduce not only infections with SARS-CoV-2 but also infections with other respiratory viruses and bacteria, reactive airway disease (eg, asthma) triggered by antigens,9 pulmonary and cardiovascular injury from inhalation of harmful respiratory particulates (eg, wildfires, smog), and toxicity from inhalation of volatile organic compounds. A once-in-decades opportunity now exists to make sustained improvements to public and private indoor air quality, reduce COVID-19 risk, and improve school, workplace, and consumer health and safety.
Nirmatrelvir Resistant SARS-CoV-2 Variants with High Fitness in Vitro
The oral protease inhibitor nirmatrelvir is expected to play a pivotal role for prevention of severe cases of coronavirus disease 2019 (COVID-19). To facilitate monitoring of potentially emerging resistance, we studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) escape from nirmatrelvir. Resistant variants selected in cell culture harbored different combinations of substitutions in the SARS-CoV-2 main protease (Mpro). Reverse genetic studies in a homologous infectious cell culture system revealed up to 80-fold resistance conferred by the combination of substitutions L50F and E166V. Resistant variants had high fitness increasing the likelihood of occurrence and spread of resistance. Molecular dynamics simulations revealed that E166V and L50F+E166V weakened nirmatrelvir-Mpro binding. The SARS-CoV-2 polymerase inhibitor remdesivir retained activity against nirmatrelvir resistant variants and combination of remdesivir and nirmatrelvir enhanced treatment efficacy compared to individual compounds. These findings have implications for monitoring and ensuring treatment programs with high efficacy against SARS-CoV-2 and potentially emerging coronaviruses.
A single intramuscular tixagevimab–cilgavimab dose provided statistically and clinically significant protection against progression to severe COVID-19 or death versus placebo in unvaccinated individuals and safety was favourable. Treating mild to moderate COVID-19 earlier in the disease course with tixagevimab–cilgavimab might lead to more favourable outcomes.
Persistence of residual SARS-CoV-2 viral antigen and RNA in tissues of patients with long COVID-19
The World Health Organization has defined long COVID-19 (LC) as a condition where patients exhibit persistent symptoms over time after its acute phase, which cannot be explained by alternative diagnosis. Since we have previously reported residual viral antigens in tissues of convalescent patients, we now aim to assess the presence of such antigens in post-convalescent tissues. Here, we established the presence of residual virus within the appendix and breast tissue of 2 patients who exhibited LC symptoms, 175 to 462 days upon positive diagnosis, using immunohistological techniques. We observed positive staining for viral nucleocapsid protein (NP) in the appendix, and tumour-adjacent region of the breast, but not within the tumour via multiplex immunohistochemistry. Notably, with RNAscope, both positive-sense and negative-sense (replicative intermediate) viral RNA were detected. As a single-stranded virus, SARS-CoV-2, have to produce a replicative intermediate as a template to synthesize new genomic RNAs. Thus, the detection of negative-sense viral RNA suggests ongoing viral replication. While viral RNA and antigen from gastrointestinal and stool samples of convalescent patients has been extensively reported, we believe this is the first study to detect viable virus. Furthermore, our positive finding in the breast tissue also corroborated with recent reports that immunocompromised patients had also experienced LC symptoms and persistent viral replication. Overall, our findings, along with emerging LC studies, raises the possibility of the gastrointestinal tract functioning as a reservoir.
The Association Between COVID-19 Mortality And The County-Level Partisan Divide In The United States
Partisan differences in attitudes toward the COVID-19 pandemic and toward the appropriateness of local policies requiring masks, social distancing, and vaccines are apparent in the United States. Previous research suggests that areas with a higher Republican vote share may experience more COVID-19 mortality, potentially as a consequence of these differences. In this observational study that captured data from a majority of US counties, we compared the number of COVID-19 deaths through October 31, 2021, among counties with differing levels of Republican vote share, using 2020 presidential election returns to characterize county political affiliation. Our analyses controlled for demographic characteristics and social determinants likely to influence COVID-19 transmission and outcomes using state fixed effects. We found a positive dose-response relationship between county-level Republican vote share and county-level COVID-19 mortality. Majority Republican counties experienced 72.9 additional deaths per 100,000 people relative to majority Democratic counties during the study period, and COVID-19 vaccine uptake explains approximately 10 percent of the difference. Our findings suggest that county-level voting behavior may act as a proxy for compliance with and support of public health measures that would protect residents from COVID-19.
June 3, 2022
The immune system is highly time-of-day dependent. Pioneering studies in the 1960s were the first to identify immune responses to be under a circadian control. Only in the last decade, however, have the molecular factors governing circadian immune rhythms been identified. These studies have revealed a highly complex picture of the interconnectivity of rhythmicity within immune cells with that of their environment. Here, we provide a global overview of the circadian immune system, focusing on recent advances in the rapidly expanding field of circadian immunology.
June 2, 2022
Omicron is the evolutionarily most distinct SARS-CoV-2 variant of concern (VOC) to date. We report that Omicron BA.1 breakthrough infection in BNT162b2-vaccinated individuals resulted in strong neutralizing activity against Omicron BA.1, BA.2 and previous SARS-CoV-2 VOCs, but not against the Omicron sublineages BA.4 and BA.5. BA.1 breakthrough infection induced a robust recall response, primarily expanding BMEM cells against epitopes shared broadly amongst variants, rather than inducing BA.1-specific B cells. The vaccination-imprinted BMEM cell pool had sufficient plasticity to be remodeled by heterologous SARS-CoV-2 spike glycoprotein exposure. While selective amplification of BMEM cells recognizing shared epitopes allows for effective neutralization of most variants that evade previously established immunity, susceptibility to escape by variants that acquire alterations at hitherto conserved sites may be heightened.
COVID-19 vaccination mandates and vaccine uptake
We evaluate the impact of government-mandated proof of vaccination requirements for access to public venues and non-essential businesses on COVID-19 vaccine uptake. We find that the announcement of a mandate is associated with a rapid and significant surge in new vaccinations (a more than 60% increase in weekly first doses), using the variation in the timing of these measures across Canadian provinces in a difference-in-differences approach. Time-series analysis for each province and for France, Italy and Germany corroborates this finding. Counterfactual simulations using our estimates suggest the following cumulative gains in the vaccination rate among the eligible population (age 12 and over) as of 31 October 2021: up to 5 percentage points (p.p.) (90% confidence interval, 3.9–5.8) for Canadian provinces, adding up to 979,000 (425,000–1,266,000) first doses in total for Canada (5 to 13 weeks after the provincial mandate announcements); 8 p.p. (4.3–11) for France (16 weeks post-announcement); 12 p.p. (5–15) for Italy (14 weeks post-announcement) and 4.7 p.p. (4.1–5.1) for Germany (11 weeks post-announcement).
Booster mRNA vaccine-doses were moderately effective in preventing infection with the omicron variant of SARS-CoV-2 for over a month after administration, which indicates their suitability as a strategy to limit the health effects of COVID-19 in periods of omicron variant domination. Estimated effectiveness was higher for mRNA-1273 compared with BNT162b2 and increased with time between completed primary vaccination and booster.
June 1, 2022
Communicating doctors’ consensus persistently increases COVID-19 vaccinations
The reluctance of people to get vaccinated represents a fundamental challenge to containing the spread of deadly infectious diseases, including COVID-19. Identifying misperceptions that can fuel vaccine hesitancy and creating effective communication strategies to overcome them are a global public health priority. Medical doctors are a trusted source of advice about vaccinations, but media reports may create an inaccurate impression that vaccine controversy is prevalent among doctors, even when a broad consensus exists. Here we show that public misperceptions about the views of doctors on the COVID-19 vaccines are widespread, and correcting them increases vaccine uptake. We implement a survey among 9,650 doctors in the Czech Republic and find that 90% of doctors trust the vaccines. Next, we show that 90% of respondents in a nationally representative sample (n = 2,101) underestimate doctors’ trust; the most common belief is that only 50% of doctors trust the vaccines. Finally, we integrate randomized provision of information about the true views held by doctors into a longitudinal data collection that regularly monitors vaccination status over 9 months. The treatment recalibrates beliefs and leads to a persistent increase in vaccine uptake. The approach demonstrated in this paper shows how the engagement of professional medical associations, with their unparalleled capacity to elicit individual views of doctors on a large scale, can help to create a cheap, scalable intervention that has lasting positive impacts on health behaviour.
Why does viral RNA sometimes persist after recovery from acute infections?
DNA viruses often persist in the body of their host, becoming latent and recurring many months or years later. By contrast, most RNA viruses cause acute infections that are cleared from the host as they lack the mechanisms to persist. However, it is becoming clear that viral RNA can persist after clinical recovery and elimination of detectable infectious virus. This persistence can either be asymptomatic or associated with late progressive disease or nonspecific lingering symptoms, such as may be the case following infection with Ebola or Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Why does viral RNA sometimes persist after recovery from an acute infection? Where does the RNA come from? And what are the consequences?
Challenges of Deciding Whether and How to Update COVID-19 Vaccines to Protect Against Variants
Seasonal influenza vaccines are updated every year, depending on what strains are circulating globally, leaving many people—especially those who still contracted COVID-19 after 2 booster shots—wondering why vaccines against SARS-CoV-2 haven’t changed as variants have come and gone.
May 31, 2022
Mask wearing in community settings reduces SARS-CoV-2 transmission
We directly analyze the effect of mask wearing on SARS-CoV-2 transmission, drawing on several datasets covering 92 regions on six continents, including the largest survey of wearing behavior (n= 20 million) [F. Kreuter et al., https://gisumd.github.io/COVID-19-API-Documentation (2020)]. Using a Bayesian hierarchical model, we estimate the effect of mask wearing on transmission, by linking reported wearing levels to reported cases in each region, while adjusting for mobility and nonpharmaceutical interventions (NPIs), such as bans on large gatherings. Our estimates imply that the mean observed level of mask wearing corresponds to a 19% decrease in the reproduction number R. We also assess the robustness of our results in 60 tests spanning 20 sensitivity analyses. In light of these results, policy makers can effectively reduce transmission by intervening to increase mask wearing.
Analysis of overdispersion in airborne transmission of COVID-19
Superspreading events and overdispersion are hallmarks of the COVID-19 pandemic. However, the specific roles and influence of established viral and physical factors related to the mechanisms of transmission, on overdispersion, remain unresolved. We, therefore, conducted mechanistic modeling of SARS-CoV-2 point-source transmission by infectious aerosols using real-world occupancy data from more than 100 000 social contact settings in ten US metropolises. We found that 80% of secondary infections are predicted to arise from approximately 4% of index cases, which show up as a stretched tail in the probability density function of secondary infections per infectious case. Individual-level variability in viral load emerges as the dominant driver of overdispersion, followed by occupancy. We then derived an analytical function, which replicates the simulated overdispersion, and with which we demonstrate the effectiveness of potential mitigation strategies. Our analysis, connecting the mechanistic understanding of SARS-CoV-2 transmission by aerosols with observed large-scale epidemiological characteristics of COVID-19 outbreaks, adds an important dimension to the mounting body of evidence with regard to airborne transmission of SARS-CoV-2 and thereby emerges as a powerful tool toward assessing the probability of outbreaks and the potential impact of mitigation strategies on large scale disease dynamics.
An mRNA booster is recommended to supplement any primary vaccine course. Heterologous and homologous three dose regimens work comparably well in preventing covid-19 infections, even against different variants. The effectiveness of three dose vaccine regimens against covid-19 related death remains uncertain.
In this retrospective cohort study of 7126 patients with COVID-19, an analysis of 1216 patients with oxygen saturation levels that were concurrently measured by pulse oximetry and arterial blood gas demonstrated that pulse oximetry overestimated arterial oxygen saturation among Asian, Black, and Hispanic patients compared with White patients. Separately, among 6673 patients with pulse oximetry measurements and available covariate data, predicted overestimation of arterial oxygen saturation levels by pulse oximetry among 1903 patients was associated with a systematic failure to identify Black and Hispanic patients who were qualified to receive COVID-19 therapy and a statistically significant delay in recognizing the guideline-recommended threshold for initiation of therapy.
May 30, 2022
An early warning system for emerging SARS-CoV-2 variants
The evolving virus and the uncertainty of predicting the trajectory of the pandemic call for strengthened surveillance and continued monitoring of SARS-CoV-2. The TAG-VE will continue to critically appraise state-of-the-art methodologies for predicting further evolution of SARS-CoV-2 and will continue to rapidly determine the threat levels posed by new variants. The pandemic is not over, and SARS-CoV-2 is spreading at a high level globally. Now is the time to enhance global sequencing capacities, focusing on widening coverage to include previous geographical and population blind spots, and to build a global consensus toward continued concerted multidisciplinary efforts, under the leadership of the WHO R&D Blueprint for action to prevent epidemics, to track and assess the threat posed by future SARS-CoV-2 variants.
Brain motor and fear circuits regulate leukocytes during acute stress
The nervous and immune systems are intricately linked1. Although psychological stress is known to modulate immune function, mechanistic pathways linking stress networks in the brain to peripheral leukocytes remain poorly understood2. Here, we show that distinct brain regions shape leukocyte distribution and function throughout the body during acute stress in mice. Using optogenetics and chemogenetics, we demonstrate that motor circuits induce rapid neutrophil mobilization from the bone marrow to peripheral tissues via skeletal muscle-derived neutrophil-attracting chemokines. Conversely, the paraventricular hypothalamus controls monocyte and lymphocyte egress from secondary lymphoid organs and blood to the bone marrow through direct, cell-intrinsic glucocorticoid signaling. These stress-induced, counter-directional, population-wide leukocyte shifts are associated with altered disease susceptibility. On the one hand, acute stress changes innate immunity by reprogramming neutrophils and directing their recruitment to sites of injury. On the other hand, corticotropin releasing hormone (CRH) neuron-mediated leukocyte shifts protect against the acquisition of autoimmunity, but impair immunity to SARS-CoV-2 and influenza infection. Collectively, these data show that distinct brain regions differentially and rapidly tailor the leukocyte landscape during psychological stress, thus calibrating the immune system’s capacity to respond to physical threats.
May 29, 2022
Main Outcomes: Composite of SARS-CoV-2 infection, COVID-19-related hospitalization, and all-cause mortality. We used cox proportional hazards modelling to estimate the hazard ratios (HR) and 95% CI for the association between receipt of tixagevimab/cilgavimab and outcomes. Results: Most (69%) tixagevimab/cilgavimab recipients were ≥65 years old, 92% were identified as immunocompromised in electronic data, and 73% had ≥3 mRNA vaccine doses or two doses of Ad26.COV2. Compared to propensity-matched controls, tixagevimab/cilgavimab-treated patients had a lower incidence of the composite COVID-19 outcome (17/1733 [1.0%] vs 206/6354 [3.2%]; HR 0.31; 95%CI, 0.18-0.53), and individually SARS-CoV-2 infection (HR 0.34; 95%CI, 0.13-0.87), COVID-19 hospitalization (HR 0.13; 95%CI, 0.02-0.99), and all-cause mortality (HR 0.36; 95%CI, 0.18-0.73). Limitations: Confounding by indication and immortal time bias. Conclusions: Using national real-world data from predominantly vaccinated, immunocompromised Veterans, administration of tixagevimab/cilgavimab was associated with lower rates of SARS-CoV-2 infection, COVID-19 hospitalization, and all-cause mortality during the Omicron surge.
Risk of incident diabetes post-COVID-19: A systematic review and meta-analysis
It remains undetermined whether burden of diabetes newly detected during acute COVID-19 persist in post-acute COVID phase. This meta-analysis was conducted to summarize the available literature and provide a pooled estimate of the risk of developing incident diabetes following hospital discharge or at least 28 days after the COVID-19 diagnosis compared to matched controls or severity matched influenza/ non-COVID-19 acute upper respiratory tract infections (AURI). Pooled analysis of 5787,027 subjects from four observational studies showed 59 % higher risk of developing incident diabetes in post-acute COVID-19 phase versus healthy controls (HR:1.59; 95 % CI:1.40–1.81, p < 0.001, I2=94 %, random-effects model). The high degree of heterogeneity in pooled estimate can be attributed to difference in demographic characteristics, hospitalization rates or disease severity between study subjects. Pooling data from three studies, higher risk of incident diabetes was also observed following COVID-19 versus severity matched non-COVID-19 respiratory tract infections (moderate-severe/hospitalized cases, HR 1.52; 95 % CI: 1.36–1.70, p < 0.01, I2=0 %, fixed-effects model; mild cases, HR 1.22; 95 % CI: 1.14–1.31, p < 0.001; I2=0 %, fixed-effects model). Majority of studies had median follow-up period of around 4 months. In view of several limitations due to retrospective design of these studies, prospective studies with long term follow-up are warranted.
May 27, 2022
Neutralization capacity of antibodies against Omicron after a prior SARS-CoV-2 infection in children and adolescents is not well studied. Therefore, we evaluated virus-neutralizing capacity against SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants by age-stratified analyses (<5, 5–11, 12–21 years) in 177 pediatric patients hospitalized with severe acute COVID-19, acute MIS-C, and in convalescent samples of outpatients with mild COVID-19 during 2020 and early 2021. Across all patients, less than 10% show neutralizing antibody titers against Omicron. Children <5 years of age hospitalized with severe acute COVID-19 have lower neutralizing antibodies to SARS-CoV-2 variants compared with patients >5 years of age. As expected, convalescent pediatric COVID-19 and MIS-C cohorts demonstrate higher neutralization titers than hospitalized acute COVID-19 patients. Overall, children and adolescents show some loss of cross-neutralization against all variants, with the most pronounced loss against Omicron. In contrast to SARS-CoV-2 infection, children vaccinated twice demonstrated higher titers against Alpha, Beta, Gamma, Delta and Omicron. These findings can influence transmission, re-infection and the clinical disease outcome from emerging SARS-CoV-2 variants and supports the need for vaccination in children.
COVID-19 in 2022—The Beginning of the End or the End of the Beginning?
If COVID-19 moves toward endemicity, then it should not disrupt everyday life. However, with ongoing transmission and with an estimated 10% to 30% of individuals experiencing long COVID symptoms after infection, this issue will require careful attention to further define the syndrome and possible intervention (such as the RECOVER cohort study at the National Institutes of Health). Data suggest that vaccination can decrease the risk of long COVID and thus continuing to focus on improving vaccination rates must remain the cornerstone of COVID-19 prevention and mitigation not only locally, but globally.
May 26, 2022
The isolation of CCoV-HuPn-2018 from a child respiratory swab indicates that more coronaviruses are spilling over to humans than previously appreciated. We determined structures of the CCoV-HuPn-2018 spike glycoprotein trimer in two distinct conformational states and show that its domain 0 recognizes sialosides. We identified that the CCoV-HuPn-2018 spike binds canine, feline and porcine aminopeptidase N (APN) orthologs, which serve as entry receptors, and determined the structure of the receptor-binding B domain in complex with canine APN. Introduction of an oligosaccharide at position N739 of human APN renders cells susceptible to CCoV-HuPn-2018 spike-mediated entry, suggesting that single nucleotide polymorphisms might account for viral detection in some individuals. Human polyclonal plasma antibodies elicited by HCoV-229E infection and a porcine coronavirus monoclonal antibody inhibit CCoV-HuPn-2018 spike-mediated entry, underscoring cross-neutralizing activity among ɑ-coronaviruses. These data pave the way for vaccine and therapeutic development targeting this zoonotic pathogen representing the 8th human-infecting coronavirus.
Humoral and cellular immune memory to four COVID-19 vaccines
Multiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be informative for understanding protective immunity against COVID-19, with particular interest in immune memory. Here, SARS-CoV-2-spike-specific immune responses to Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, Janssen Ad26.COV2.S and Novavax NVX-CoV2373 were examined longitudinally for 6 months. 100% of individuals made memory CD4+ T cells, with cTfh and CD4-CTL highly represented after mRNA or NVX-CoV2373 vaccination. mRNA vaccines and Ad26.COV2.S induced comparable CD8+ T cell frequencies, though only detectable in 60-67% of subjects at 6 months. A differentiating feature of Ad26.COV2.S immunization was a high frequency of CXCR3+ memory B cells. mRNA vaccinees had substantial declines in antibodies, while memory T and B cells were comparatively stable. These results may also be relevant for insights against other pathogens.
Our statistical analysis showed that the effective reproduction numbers of these L452R/M/Q-bearing BA.2-related Omicron variants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1 and BA.2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. Furthermore, infection experiments using hamsters indicated that BA.4/5 is more pathogenic than BA.2. Altogether, our multiscale investigations suggest that the risk of L452R/M/Q-bearing BA.2-related Omicron variants, particularly BA.4 and BA.5, to global health is potentially greater than that of original BA.2.
SARS-CoV-2 Omicron BA.2.12.1, BA.4, and BA.5 subvariants evolved to extend antibody evasion
We now report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. On the other hand, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike residue L452 found in both BA.2.12.1 and BA.4/5 facilitates escape from some antibodies directed to the so-called Class 2 and Class 3 regions of the receptor-binding domain (RBD). The F486V mutation found in BA.4/5 facilitates escape from certain Class 1 and Class 2 antibodies to the RBD but compromises the spike affinity for the cellular receptor ACE2. The R493Q reversion mutation, however, restores receptor affinity and consequently the fitness of BA.4/5. Among therapeutic antibodies authorized for clinical use, only bebtelovimab (LY-COV1404) retains full potency against both BA.2.12.1 and BA.4/5. The Omicron lineage of SARS-CoV-2 continues to evolve, successively yielding subvariants that are not only more transmissible but also more evasive to antibodies.
Findings from case-control analysis broadly confirmed those of primary analysis. Interpretation Amid the Omicron BA.2.2 wave, early initiation of oral antivirals among non-institutionalised COVID-19 patients was associated with reduced risks of mortality and in-hospital outcomes. Nirmatrelvir/ritonavir use was associated with greater and more consistent protection than molnupiravir.
May 25, 2022
Long COVID after breakthrough SARS-CoV-2 infection
The post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection—also referred to as Long COVID—have been described, but whether breakthrough SARS-CoV-2 infection (BTI) in vaccinated people results in post-acute sequelae is not clear. In this study, we used the US Department of Veterans Affairs national healthcare databases to build a cohort of 33,940 individuals with BTI and several controls of people without evidence of SARS-CoV-2 infection, including contemporary (n = 4,983,491), historical (n = 5,785,273) and vaccinated (n = 2,566,369) controls. At 6 months after infection, we show that, beyond the first 30 days of illness, compared to contemporary controls, people with BTI exhibited a higher risk of death (hazard ratio (HR) = 1.75, 95% confidence interval (CI): 1.59, 1.93) and incident post-acute sequelae (HR = 1.50, 95% CI: 1.46, 1.54), including cardiovascular, coagulation and hematologic, gastrointestinal, kidney, mental health, metabolic, musculoskeletal and neurologic disorders. The results were consistent in comparisons versus the historical and vaccinated controls. Compared to people with SARS-CoV-2 infection who were not previously vaccinated (n = 113,474), people with BTI exhibited lower risks of death (HR = 0.66, 95% CI: 0.58, 0.74) and incident post-acute sequelae (HR = 0.85, 95% CI: 0.82, 0.89). Altogether, the findings suggest that vaccination before infection confers only partial protection in the post-acute phase of the disease; hence, reliance on it as a sole mitigation strategy may not optimally reduce long-term health consequences of SARS-CoV-2 infection. The findings emphasize the need for continued optimization of strategies for primary prevention of BTI and will guide development of post-acute care pathways for people with BTI.
Increased receptor affinity of SARS-CoV-2: a new immune escape mechanism
SARS-CoV-2 has proven to be a rapidly evolving RNA virus with steadily emerging new viral variants. Several of them show enhanced infectivity and/or escape from neutralization by monoclonal antibodies (mAbs), and some were termed variants of concern (VoC).
Effectiveness of Homologous and Heterologous Covid-19 Boosters against Omicron
For persons who received a single dose of the Ad26.COV2S vaccine (Johnson & Johnson–Janssen) against coronavirus disease 2019 (Covid-19), a booster dose of a messenger RNA (mRNA) vaccine at least 2 months after the primary dose is recommended. Recipients of Ad26.COV2.S for both the primary and booster doses may receive a second booster dose of an mRNA Covid-19 vaccine at least 4 months after the first Ad26.COV2.S booster dose. Immunogenicity data from a phase 1–2 clinical trial conducted before B.1.1.529 and the BA sublineages of omicron emerged showed that increases in the titers of binding and neutralizing antibodies with heterologous boosting were similar to or greater than the increases with homologous boosting.
Distinct antigenic properties of the SARS-CoV-2 Omicron lineages BA.4 and BA.5
Over the course of the pandemic variants have arisen at a steady rate. The most recent variants to emerge, BA.4 and BA.5, form part of the Omicron lineage and were first found in Southern Africa where they are driving the current wave of infection. In this report, we perform an in-depth characterisation of the antigenicity of the BA.4/BA.5 Spike protein by comparing sera collected post-vaccination, post-BA.1 or BA.2 infection, or post breakthrough infection of vaccinated individuals with the Omicron variant. In addition, we assess sensitivity to neutralisation by commonly used therapeutic monoclonal antibodies. We find sera collected post-vaccination have a similar ability to neutralise BA.1, BA.2 and BA.4/BA.5. In contrast, in the absence of vaccination, prior infection with BA.2 or, in particular, BA.1 results in an antibody response that neutralises BA.4/BA.5 poorly. Breakthrough infection with Omicron in vaccinees leads to a broad neutralising response against the new variants. The sensitivity of BA.4/BA.5 to neutralisation by therapeutic monoclonal antibodies was similar to that of BA.2. These data suggest BA.4/BA.5 are antigenically distinct from BA.1 and, to a lesser extent, BA.2. The enhanced breadth of neutralisation observed following breakthrough infection with Omicron suggests that vaccination with heterologous or multivalent antigens may represent viable strategies for the development of cross-neutralising antibody responses.
Protection and Waning of Natural and Hybrid Immunity to SARS-CoV-2
Among persons who had been previously infected with SARS-CoV-2 (regardless of whether they had received any dose of vaccine or whether they had received one dose before or after infection), protection against reinfection decreased as the time increased since the last immunity-conferring event; however, this protection was higher than that conferred after the same time had elapsed since receipt of a second dose of vaccine among previously uninfected persons. A single dose of vaccine after infection reinforced protection against reinfection.
Individuals who contract Covid-19 often experience problems with memory, attention, andconcentration, even after recovering from the initial illness. In the current manuscript, we argue that these symptoms are likely to manifest as cognitive failures in the workplace. Downstream, cognitive failures were expected to be associated with decreased task performance and increased turnover intentions. We collected data from a sample of working adults who either had (n = 45) or had not (n = 49) contracted Covid-19 at least one month prior to the study. Both groups were matched on key demographic characteristics. As anticipated, individuals who had contracted Covid-19 reported significantly more cognitive failures at work, relative to individuals who did not. More so, having contracted Covid-19 had significant indirect effects on task performance and turnover intentions via cognitive failure. These results indicate that beyond physical harm, Covid-19 can also have a detrimental influence on an individual’s capacity to perform at work.
May 24, 2022
A Longitudinal Study of COVID-19 Sequelae and Immunity: Baseline Findings
A high burden of persistent symptoms was observed in persons after COVID-19. Extensive diagnostic evaluation revealed no specific cause of reported symptoms in most cases. Antibody levels were highly variable after COVID-19.
COVID-19 survivors have twice the risk for developing pulmonary embolism or respiratory conditions; one in five COVID-19 survivors aged 18–64 years and one in four survivors aged ≥65 years experienced at least one incident condition that might be attributable to previous COVID-19.
COVID-19 vaccine effectiveness against the omicron (BA.2) variant in England
The omicron (B.1.1.529) variant, first detected in the UK on Nov 27, 2021, rapidly became the dominant strain, due in part to reduced vaccine effectiveness. An increase in sequenced cases of the omicron sub-lineage BA.2 was observed in the week beginning on Jan 3, 2022. BA.2 has a growth advantage over BA.1 and has become the dominant strain in the UK at the time of writing. Neutralisation assays using monoclonal antibodies have suggested a small antigenic difference between BA.1 and BA.2, although sera from individuals with booster vaccinations neutralise both variants similarly.
Co-infection with SARS-CoV-2 omicron BA.1 and BA.2 subvariants in a non-vaccinated woman
Circulation of contagious SARS-CoV-2 variants and suboptimal vaccine protection create the conditions for simultaneous infections with multiple strains, which could generate inter-lineage SARS-CoV-2 recombinants with novel unpredictable features. Mixed infections have been reported since the first epidemic waves. Co-infection with omicron and delta have been found in immunocompetent and immunocompromised patients living in different geographical areas. Because these variants are characterised by different genomic sequences, their co-presence can be identified promptly. However, recombination between closely related variants is difficult to identify but can also occur. A total of 637 cases of the omicron BA.1 and BA.2 recombinant, known as XE, have been confirmed in the UK up to now, and the number is increasing. These data also suggest that intralineage recombination generates highly transmissible chimeric strains. It is necessary to detect all co-infections to minimise the risk of recombination.
Analysis of 6.4 million SARS-CoV-2 genomes identifies mutations associated with fitness
Repeated emergence of SARS-CoV-2 variants with increased fitness underscores the value of rapid detection and characterization of new lineages. We have developed PyR0, a hierarchical Bayesian multinomial logistic regression model that infers relative prevalence of all viral lineages across geographic regions, detects lineages increasing in prevalence, and identifies mutations relevant to fitness. Applying PyR0 to all publicly available SARS-CoV-2 genomes, we identify numerous substitutions that increase fitness, including previously identified spike mutations and many non-spike mutations within the nucleocapsid and nonstructural proteins. PyR0 forecasts growth of new lineages from their mutational profile, ranks the fitness of lineages as new sequences become available, and prioritizes mutations of biological and public health concern for functional characterization.
Understanding and Improving Recovery From COVID-19
The COVID-19 pandemic emerged at a time when we had won our way to a hilltop where many diseases are treatable. Improved treatment means that our health systems need to care for an increasing number of survivors of all types, including cancer survivors, older adults living with multiple comorbid conditions, and survivors of severe critical illnesses struggling to reintegrate into society. Humbled and cast down as we were by the tragedy of the worst of the COVID-19 pandemic, there was reassurance in the fact that many patients with SARS-CoV-2 infection were asymptomatic or had mild acute illness. We were unprepared for the onslaught of survivors of acute SARS-CoV-2 infection with persistent symptoms long after acute illness. Many of these patients present requesting diagnoses, expecting treatment, and worrying about their future lives in the shadow of COVID-19. Too often, these patients suffer the injustices of not being believed, being misdiagnosed as having anxiety disorder, or having their symptoms misattributed to pandemic stress.
May 23, 2022
Variant-specific symptoms of COVID-19 among 1,542,510 people in England
Infection with SARS-CoV-2 virus is associated with a wide range of symptoms. The REal-time Assessment of Community Transmission -1 (REACT-1) study has been monitoring the spread and clinical manifestation of SARS-CoV-2 among random samples of the population in England from 1 May 2020 to 31 March 2022. We show changing symptom profiles associated with the different variants over that period, with lower reporting of loss of sense of smell and taste for Omicron compared to previous variants, and higher reporting of cold-like and influenza-like symptoms, controlling for vaccination status. Contrary to the perception that recent variants have become successively milder, Omicron BA.2 was associated with reporting more symptoms, with greater disruption to daily activities, than BA.1. With restrictions lifted and routine testing limited in many countries, monitoring the changing symptom profiles associated with SARS-CoV-2 infection and induced changes in daily activities will become increasingly important.
Airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or other pathogens is probably increased during indoor exercise, but data on the emission of aerosol particles by an exercising individual are lacking. Here, we report that aerosol particle emission increases on average 132-fold from 580 ± 489 particles/min at rest to 76,200 ± 48,000 particles/min during maximal exercise. Aerosol particle emission increases moderately up to an exercise intensity of ≈2 W/kg and exponentially at higher exercise intensities. These data not only explain SARS-CoV-2 transmissions during indoor group exercise but also can be used to design better targeted mitigation measures for physical activity indoors such as physical education in school, dance events during weddings, or high-intensity gym classes such as spinning.
Further antibody escape by Omicron BA.4 and BA.5 from vaccine and BA.1 serum
The Omicron lineage of SARS-CoV-2, first described in November 2021, spread rapidly to become globally dominant and has split into a number of sub-lineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africa's Gauteng region uncovered two new sub-lineages, BA.4 and BA.5 which are taking over locally, driving a new wave. BA.4 and BA.5 contain identical spike sequences and, although closely related to BA.2, contain further mutations in the receptor binding domain of spike. Here, we study the neutralization of BA.4/5 using a range of vaccine and naturally immune serum and panels of monoclonal antibodies. BA.4/5 shows reduced neutralization by serum from triple AstraZeneca or Pfizer vaccinated individuals compared to BA.1 and BA.2. Furthermore, using serum from BA.1 vaccine breakthrough infections there are likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections.
Multisystem involvement is common in post-COVID-19 syndrome
Overall, we found that the COVID-19 illness trajectory includes persistent cardio-renal inflammation, hemostatic pathway activation and lung involvement. Our results demonstrate a link between the post-COVID-19 syndrome and multisystem disease, which partly explains the lingering impairments in patient-reported health-related quality of life, physical function and psychological well-being after COVID-19. The implication of multisystem injury pathways as mediators of post-COVID-19 syndrome should help to inform clinical guideline updates4, and the findings support the prioritization of targeted preventive therapy development for post-COVID-19 syndromes in hospitalized patients.
A multisystem, cardio-renal investigation of post-COVID-19 illness
Compared to controls (n = 29), at 28–60 days post-discharge, people with COVID-19 (n = 159; mean age, 55 years; 43% female) had persisting evidence of cardio-renal involvement and hemostasis pathway activation. The adjudicated likelihood of myocarditis was ‘very likely’ in 21 (13%) patients, ‘probable’ in 65 (41%) patients, ‘unlikely’ in 56 (35%) patients and ‘not present’ in 17 (11%) patients. At 28–60 days post-discharge, COVID-19 was associated with worse health-related quality of life (EQ-5D-5L score 0.77 (0.23) versus 0.87 (0.20)), anxiety and depression (PHQ-4 total score 3.59 (3.71) versus 1.28 (2.67)) and aerobic exercise capacity reflected by predicted maximal oxygen utilization (20.0 (7.6) versus 29.5 (8.0) ml/kg/min) (all P < 0.01). During follow-up (mean, 450 days), 24 (15%) patients and two (7%) controls died or were rehospitalized, and 108 (68%) patients and seven (26%) controls received outpatient secondary care (P = 0.017). The illness trajectory of patients after hospitalization with COVID-19 includes persisting multisystem abnormalities and health impairments that could lead to substantial demand on healthcare services in the future.
We describe relapse of COVID-19 symptoms and SARS-CoV-2 viral load following nirmatrelvir/ritonavir (NM/R) in 10 non-immunocompromised patients aged 31 to 71-years-old. Most patients improved rapidly after treatment with NM/R and had negative antigen or PCR tests prior to relapse on Days 9-12 of their illness. Relapse symptoms were described most frequently as cold symptoms, though some patients experiencing a recurrence of fatigue and headache. All relapses resolved without additional antiviral treatment. Viral load during relapse was comparable to levels during initial infection. Sequencing in three patients indicated that relapse was not due to a treatment-emergent mutation or infection with a different viral strain. One symptomatic and one presymptomatic patient transmitted SARS-CoV-2 to family members during relapse. The presence of high viral load and the occurrence of two transmission events suggest that patients with relapse should isolate until antigen testing is negative.
May 20, 2022
SARS-CoV-2 variants of concern and variants under investigation in England
Updated growth modelling suggests BA.4 and BA.5 are likely to have a growth advantage overBA.2, including within the UK. This is based on small numbers of cases and there is a high degree of uncertainty. However, together with the laboratory data suggesting some degree of immune escape, BA.4 and BA.5 have been designated Variants of Concern, as this classification is intended to provide an early warning of potential risk of increased community transmission. There is no data to determine the impact of these variants on the hospital admissions in the UK.
May 19, 2022
Potent cross-reactive antibodies following Omicron breakthrough in vaccinees
Highly transmissible Omicron variants of SARS-CoV-2 currently dominate globally. Here, we compare neutralization of Omicron BA.1, BA.1.1 and BA.2. BA.2 RBD has slightly higher ACE2 affinity than BA.1 and slightly reduced neutralization by vaccine serum, possibly associated with its increased transmissibility. Neutralization differences between sub-lineages for mAbs (including therapeutics) mostly arise from variation in residues bordering the ACE2 binding site, however, more distant mutations S371F (BA.2) and R346K (BA.1.1) markedly reduce neutralization by therapeutic antibody Vir-S309. In-depth structure-and-function analyses of 27 potent RBD-binding mAbs isolated from vaccinated volunteers following breakthrough Omicron-BA.1 infection reveals that they are focussed in two main clusters within the RBD, with potent right-shoulder antibodies showing increased prevalence. Selection and somatic maturation have optimized antibody potency in less-mutated epitopes and recovered potency in highly mutated epitopes. All 27 mAbs potently neutralize early pandemic strains and many show broad reactivity with variants of concern.\
Neutralization Escape by the SARS-CoV-2 Omicron Variants BA.2.12.1 and BA.4/BA.5
Multiple lineages of the SARS-CoV-2 Omicron variant (B.1.1.529) have emerged, and BA.1 and BA.2 have demonstrated substantial escape from neutralizing antibodies (NAbs). BA.2.12.1 has now become dominant in the United States, and BA.4 and BA.5 have become dominant in South Africa. Our data show that BA.2.12.1 and BA.4/BA.5 substantially escape NAbs induced by both vaccination and infection. Moreover, BA.4/BA.5 NAb titers, and to lesser extent BA.2.12.1 NAb titers, were lower than BA.1 and BA.2 NAb titers, suggesting that the SARS-CoV-2 Omicron variant has continued to evolve with increasing neutralization escape. These findings have important public health implications and provide immunologic context for the current surges with BA.2.12.1 and BA.4/BA.5 in populations with high rates of vaccination and BA.1/BA.2 infection.
May 18, 2022
Trajectory of long covid symptoms after covid-19 vaccination: community based cohort study
The likelihood of long covid symptoms was observed to decrease after covid-19 vaccination and evidence suggested sustained improvement after a second dose, at least over the median follow-up of 67 days. Vaccination may contribute to a reduction in the population health burden of long covid, although longer follow-up is needed.
Are vaccines a potential treatment for long covid?
Benefits are possible, but we need more evidence and a mechanism of action
May 15, 2022
In this randomized clinical trial that included 400 adults with acute hypoxemic respiratory failure from COVID-19, awake prone positioning compared with usual care resulted in endotracheal intubation at 30 days in 34.1% vs 40.5% of participants, respectively. Although the hazard ratio was 0.81, the result was not statistically significant.
May 13, 2022
In a test-negative, case-control study conducted from December 2021 to February 2022 during Omicron variant predominance that included 121 952 tests from sites across the US, estimated vaccine effectiveness against symptomatic infection for children 5 to 11 years of age was 60.1% 2 to 4 weeks after dose 2 and 28.9% during month 2 after dose 2. Among adolescents 12 to 15 years of age, estimated vaccine effectiveness was 59.5% 2 to 4 weeks after dose 2 and 16.6% during month 2; estimated booster dose effectiveness in adolescents 2 to 6.5 weeks after the booster was 71.1%.
The recent emergence of the Omicron variant has raised concerns on vaccine efficacy and the urgent need to study more efficient vaccination strategies. Here we observed that an mRNA vaccine booster in individuals vaccinated with two doses of inactivated vaccine significantly increased the plasma level of specific antibodies that bind to the receptor-binding domain (RBD) or the spike (S) ectodomain (S1 + S2) of both the G614 and the Omicron variants, compared to two doses of homologous inactivated vaccine. The level of RBD- and S-specific IgG antibodies and virus neutralization titers against variants of concern in the heterologous vaccination group were similar to that in individuals receiving three doses of homologous mRNA-vaccine or a boost of mRNA vaccine after infection, but markedly higher than that in individuals receiving three doses of a homologous inactivated vaccine. This heterologous vaccination regime furthermore significantly enhanced the RBD-specific memory B cell response and S1-specific T cell response, compared to two or three doses of homologous inactivated vaccine. Our study demonstrates that mRNA vaccine booster in individuals vaccinated with inactivated vaccines can be highly beneficial, as it markedly increases the humoral and cellular immune responses against the virus, including the Omicron variant.
May 12, 2022
Effect of mRNA Vaccine Boosters against SARS-CoV-2 Omicron Infection in Qatar
The messenger RNA (mRNA) boosters were highly effective against symptomatic delta infection, but they were less effective against symptomatic omicron infection. However, with both variants, mRNA boosters led to strong protection against Covid-19–related hospitalization and death.
May 11, 2022
Evaluation of mRNA-1273 Covid-19 Vaccine in Children 6 to 11 Years of Age
Two 50-μg doses of the mRNA-1273 vaccine were found to be safe and effective in inducing immune responses and preventing Covid-19 in children 6 to 11 years of age; these responses were noninferior to those in young adults.
Regardless of initial disease severity, COVID-19 survivors had longitudinal improvements in physical and mental health, with most returning to their original work within 2 years; however, the burden of symptomatic sequelae remained fairly high. COVID-19 survivors had a remarkably lower health status than the general population at 2 years. The study findings indicate that there is an urgent need to explore the pathogenesis of long COVID and develop effective interventions to reduce the risk of long COVID.
May 10, 2022
Instructing durable humoral immunity for COVID-19 and other vaccinable diseases
Many aspects of SARS-CoV-2 have fully conformed with the principles established by decades of viral immunology research, ultimately leading to the crowning achievement of highly effective COVID-19 vaccines. Nonetheless, the pandemic has also exposed areas where our fundamental knowledge is thinner. Some key unknowns are the duration of humoral immunity post-primary infection or vaccination, and for how long booster shots confer protection. As a corollary, if protection does not last as long as desired, what are some ways it can be improved? Here, I discuss lessons from other infections and vaccines that point to several key features that influence durable antibody production and the perseverance of immunity. These include 1) the specific innate sensors that are initially triggered; 2) the kinetics of antigen delivery and persistence; 3) the starting B cell receptor (BCR) avidity and antigen valency; 4) the memory B cell subsets that are recalled by boosters. I further highlight the fundamental B cell-intrinsic and -extrinsic pathways which, if understood better, would provide a rational framework for vaccines to reliably provide durable immunity.
Imprinted antibody responses against SARS-CoV-2 Omicron sublineages
SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters result in potent plasma neutralizing activity against Omicron BA.1 and BA.2 and that breakthrough infections, but not vaccination-only, induce neutralizing activity in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1 and BA.2 receptor-binding domains whereas Omicron primary infections elicit B cells of narrow specificity. While most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant antibody, that is unaffected by any Omicron lineage spike mutations and is a strong candidate for clinical development.
Identifying antibodies that neutralize these variants of concern and determining their prevalence are important goals for understanding immune protection. To determine the Delta- and Omicron BA.1-variant specificity of B cell repertoires established by an initial Wuhan strain infection, we measured neutralization potencies of 73 antibodies from an unbiased survey of the early memory B cell response. Antibodies recognizing each of three, previously defined, epitopic regions on the spike receptor-binding domain (RBD) varied in neutralization potency and variant-escape resistance. The ACE2 binding surface (“RBD-2”) harbored the binding sites of the neutralizing antibodies with highest potency but with the greatest sensitivity to viral escape; two other epitopic regions on the RBD (“RBD-1 and “RBD-3”) bound antibodies of more modest potency but greater breadth. The structures of several Fab:spike complexes that neutralized all five variants of concern tested, including one Fab each from the RBD-1, -2 and -3 clusters, illustrated the determinants of broad neutralization and showed that B cell repertoires can have specificities that avoid immune escape driven by widely distributed (“public”) antibodies. The structure of the RBD-2-binding, broad neutralizer shows why it retains neutralizing activity for Omicron BA.1, unlike most others in the same public class. Our results correlate with real-world data on vaccine efficacy, which indicate mitigation of disease caused by Omicron BA.1.
Persistent serum protein signatures define an inflammatory subset of long COVID
Long COVID or post-acute sequelae of SARS-CoV-2 (PASC) is a clinical syndrome featuring diverse symptoms that can persist for months after acute SARS-CoV-2 infection. The etiologies are unknown but may include persistent inflammation, unresolved tissue damage, or delayed clearance of viral protein or RNA. Attempts to classify subsets of PASC by symptoms alone have been unsuccessful. To molecularly define PASC, we evaluated the serum proteome in longitudinal samples from 55 PASC individuals with symptoms lasting ≥60 days after onset of acute infection and compared this to symptomatically recovered SARS-CoV-2 infected and uninfected individuals. We identified subsets of PASC with distinct signatures of persistent inflammation. Type II interferon signaling and canonical NF-κB signaling (particularly associated with TNF), were the most differentially enriched pathways. These findings help to resolve the heterogeneity of PASC, identify patients with molecular evidence of persistent inflammation, and highlight dominant pathways that may have diagnostic or therapeutic relevance.
Modeling transmission of SARS-CoV-2 Omicron in China
We find that the level of immunity induced by the March 2022 vaccination campaign would be insufficient to prevent an Omicron wave that would result in exceeding critical care capacity with a projected intensive care unit peak demand of 15.6-times the existing capacity and causing approximately 1.55 million deaths. However, we also estimate that protecting vulnerable individuals by ensuring accessibility to vaccines and antiviral therapies, and maintaining implementation of non-pharmaceutical interventions could be sufficient to prevent overwhelming the healthcare system, suggesting that these factors should be points of emphasis in future mitigation policies.
May 9, 2022
The clinical progress of mRNA vaccines and immunotherapies
The emergency use authorizations (EUAs) of two mRNA-based severe acute respiratory syndrome coronavirus (SARS-CoV)-2 vaccines approximately 11 months after publication of the viral sequence highlights the transformative potential of this nucleic acid technology. Most clinical applications of mRNA to date have focused on vaccines for infectious disease and cancer for which low doses, low protein expression and local delivery can be effective because of the inherent immunostimulatory properties of some mRNA species and formulations. In addition, work on mRNA-encoded protein or cellular immunotherapies has also begun, for which minimal immune stimulation, high protein expression in target cells and tissues, and the need for repeated administration have led to additional manufacturing and formulation challenges for clinical translation. Building on this momentum, the past year has seen clinical progress with second-generation coronavirus disease 2019 (COVID-19) vaccines, Omicron-specific boosters and vaccines against seasonal influenza, Epstein–Barr virus, human immunodeficiency virus (HIV) and cancer. Here we review the clinical progress of mRNA therapy as well as provide an overview and future outlook of the transformative technology behind these mRNA-based drugs.
May 8, 2022
Antibody Evasion of SARS-CoV-2 Omicron BA.1, BA.1.1, BA.2 and BA.3 Sub-lineages
The SARS-CoV-2 Omicron variant has evolved into four sub-lineages, BA.1, BA.1.1, BA.2 and BA.3, with BA.2 becoming dominant worldwide. We and others have reported antibody evasion of BA.1 and BA.2, but side-by-side comparisons of Omicron sub-lineages to vaccine-elicited or monoclonal antibody (mAb)-mediated neutralization are necessary. Using VSV-based pseudovirus, we report that sera from individuals vaccinated by two doses of an inactivated whole-virion vaccine shows weak to no neutralization activity, while homologous or heterologous boosters markedly improve neutralization titers against all Omicron sub-lineages. We also present neutralization profiles against a 20-mAb panel, including 10 authorized or approved, against the Omicron sub-lineages, along with mAb mapping against single or combinatorial spike mutations. Most mAbs lost neutralizing activity, while some demonstrate distinct neutralization patterns among Omicron sub-lineages, reflecting antigenic differences. Collectively, our results suggest the Omicron sub-lineages threaten the neutralization efficacy of current vaccines and antibody therapeutics, highlighting the importance of vaccine boosters.
May 7, 2022
Our data suggest that COVID-19 vaccine is protective against post-acute sequelae of SARS-CoV-2 (PASC) symptoms, new onset of health conditions, and mortality.
May 6, 2022
Analysis of COVID-19 surveillance and vaccination data from approximately 15,000 skilled nursing facilities found that, compared with primary series vaccination only, an additional or booster dose provided greater protection (relative VE = 46.9%) against SARS-CoV-2 infection during Omicron variant predominance.
In this cross-sectional study of 278 participants self-performing SARS-CoV-2 RADT in an intended-use setting, the accuracy of RADT interpretation was poor when the manufacturer’s instructions were used. A modified quick reference guide was associated with significantly better user performance.
In this cohort study of 1958 inpatients with serious mental illness in a statewide psychiatric hospital system, the use of second-generation antipsychotic medications was associated with a decreased risk of COVID-19 infection; the largest association was observed with the use of paliperidone. Valproic acid use was associated with an increased risk of infection.
May 5, 2022
Effect of Early Treatment with Ivermectin among Patients with Covid-19
Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19.
May 2, 2022
Association of SARS-CoV-2 Infection During Pregnancy With Maternal and Perinatal Outcomes
This Canadian surveillance study included 6012 completed pregnancies between March 2020 and October 2021. Among cases of infection during pregnancy compared with cases of infection among the general Canadian population of reproductive-age female individuals, there was a significantly increased risk of SARS-CoV-2–related hospitalization (relative risk, 2.65) and intensive care unit admission (relative risk, 5.46). Among cases of infection during pregnancy compared with pregnant individuals without SARS-CoV-2 infection, there was a significantly increased risk of preterm birth (relative risk, 1.63).
COVID-19 Vaccination—Becoming Part of the New Normal
As the US emerges from the recent Omicron surge of the COVID-19 pandemic following close to a million deaths in the country attributable to COVID-19, many people are hoping that the worst is over.1 Widespread vaccine- and infection-induced immunity, combined with the availability of effective therapeutics, could blunt the effects of future outbreaks. Nonetheless, it is time to accept that the presence of SARS-CoV-2, the virus that causes COVID-19, is the new normal. It will likely circulate globally for the foreseeable future, taking its place alongside other common respiratory viruses such as influenza. And it likely will require similar annual consideration for vaccine composition updates in consultation with the US Food and Drug Administration (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC). A recent meeting of the VRBPAC on April 6, 2022, resulted in a lively discussion and agreement on many considerations for planning for upcoming approaches to COVID-19 vaccine strain composition decision-making, development, and recommendations.
May 1, 2022
Omicron sub-lineages BA.4/BA.5 escape BA.1 infection elicited neutralizing immunity
Absolute BA.4 and BA.5 neutralization levels were about 5-fold higher in this group versus unvaccinated BA.1 infected participants. The observed escape of BA.4 and BA.5 from BA.1 elicited immunity is more moderate than of BA.1 against previous immunity. However, the low absolute neutralization levels for BA.4 and BA.5, particularly in the unvaccinated group, are unlikely to protect well against symptomatic infection. This may indicate that, based on neutralization escape, BA.4 and BA.5 have potential to result in a new infection wave.
Evidence for Aerosol Transfer of SARS-CoV2-specific Humoral Immunity
Abstract. Despite the obvious knowledge that infectious particles can be shared through respiration, whether other constituents of the nasal/oral fluids can be passed between hosts has surprisingly never even been postulated, let alone investigated. The circumstances of the present pandemic facilitated a unique opportunity to fully examine this provocative idea. The data we show provides evidence for a new mechanism by which herd immunity may be manifested, the aerosol transfer of antibodies between immune and non- immune hosts.
The performance of wearable sensors in the detection of SARS-CoV-2 infection: a systematic review
Containing the COVID-19 pandemic requires rapidly identifying infected individuals. Subtle changes in physiological parameters (such as heart rate, respiratory rate, and skin temperature), discernible by wearable devices, could act as early digital biomarkers of infections. Our primary objective was to assess the performance of statistical and algorithmic models using data from wearable devices to detect deviations compatible with a SARS-CoV-2 infection. We searched MEDLINE, Embase, Web of Science, the Cochrane Central Register of Controlled Trials (known as CENTRAL), International Clinical Trials Registry Platform, and ClinicalTrials.gov on July 27, 2021 for publications, preprints, and study protocols describing the use of wearable devices to identify a SARS-CoV-2 infection. Of 3196 records identified and screened, 12 articles and 12 study protocols were analysed. Most included articles had a moderate risk of bias, as per the National Institute of Health Quality Assessment Tool for Observational and Cross-Sectional Studies. The accuracy of algorithmic models to detect SARS-CoV-2 infection varied greatly (area under the curve 0·52–0·92). An algorithm's ability to detect presymptomatic infection varied greatly (from 20% to 88% of cases), from 14 days to 1 day before symptom onset. Increased heart rate was most frequently associated with SARS-CoV-2 infection, along with increased skin temperature and respiratory rate. All 12 protocols described prospective studies that had yet to be completed or to publish their results, including two randomised controlled trials. The evidence surrounding wearable devices in the early detection of SARS-CoV-2 infection is still in an early stage, with a limited overall number of studies identified. However, these studies show promise for the early detection of SARS-CoV-2 infection. Large prospective, and preferably controlled, studies recruiting and retaining larger and more diverse populations are needed to provide further evidence.
April 29, 2022
Continued Emergence and Evolution of Omicron in South Africa: New BA.4 and BA.5 lineages
South Africa’s fourth COVID-19 wave was driven predominantly by three lineages (BA.1, BA.2 and BA.3) of the SARS-CoV-2 Omicron variant of concern. We have now identified two new lineages, BA.4 and BA.5. The spike proteins of BA.4 and BA.5 are identical, and comparable to BA.2 except for the addition of 69-70del, L452R, F486V and the wild type amino acid at Q493. The 69-70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure with the TaqPath™ COVID-19 qPCR assay. BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa from the first week of April 2022 onwards. Using a multinomial logistic regression model, we estimate growth advantages for BA.4 and BA.5 of 0.08 (95% CI: 0.07 - 0.09) and 0.12 (95% CI: 0.09 - 0.15) per day respectively over BA.2 in South Africa.
The results of this cohort study of home antigen tests suggest that sensitivity for SARS-CoV-2 was moderate compared with RT-PCR and high compared with viral culture. The results also suggest that symptomatic individuals with an initial negative home antigen test result for SARS-CoV-2 infection should test again 1 to 2 days later because test sensitivity peaked several days after illness onset and improved with repeated testing.
Prior heterologous SARS-CoV-2 infection provided substantial and sustained protection against Omicron hospitalization, greatest among those also vaccinated. In the context of program goals to prevent severe outcomes and preserve healthcare system capacity, >2 doses of ancestral Wuhan-like vaccine may be of marginal incremental value to previously-infected individuals.
Microbiota-derived metabolites or components are the main mediators of microbiota-host interactions that influence host immunity. Hence, we discuss the potential mechanisms by which microbiota-derived metabolites or components modulate the host immune responses to SARS-CoV-2 infection. Finally, we review and discuss a variety of possible microbiota-based prophylaxes and therapies for COVID-19 and PACS, including fecal microbiota transplantation (FMT), probiotics, prebiotics, microbiota-derived metabolites, and engineered symbiotic bacteria. This treatment strategy could modulate host microbiota and mitigate virus-induced inflammation.
The Pandemic Determinants of Health
Today my clinic began with a young adult coming in for follow-up for depression and needing paperwork completed for mental health–related medical leave. This was followed by an older adult whose visit notes read “annual visit, last seen 2019.” Next was another patient scheduled for an annual examination, who left with a diagnosis of complicated grief following a family member’s recent death from COVID-19, someone they had begged to get vaccinated. Then I switched gears to a telemedicine video visit with a new patient establishing care. This patient had been undergoing a long, inconclusive workup for chronic dyspnea. Since then they had rarely left their home, aside from essential activities.
April 28, 2022
Significant person-to-person variation in infectious virus shedding suggests that individual-level heterogeneity in viral dynamics contributes to ‘superspreading’. Viral genome loads often peaked days earlier in saliva than in nasal swabs, indicating strong tissue compartmentalization and suggesting that saliva may serve as a superior sampling site for early detection of infection. Viral loads and clearance kinetics of Alpha (B.1.1.7) and previously circulating non-variant-of-concern viruses were mostly indistinguishable, indicating that the enhanced transmissibility of this variant cannot be explained simply by higher viral loads or delayed clearance. These results provide a high-resolution portrait of SARS-CoV-2 infection dynamics and implicate individual-level heterogeneity in infectiousness in superspreading.
Climate change increases cross-species viral transmission risk
We predict that species will aggregate in new combinations at high elevations, in biodiversity hotspots, and in areas of high human population density in Asia and Africa, driving the novel cross-species transmission of their viruses an estimated 4,000 times. Because of their unique dispersal capacity, bats account for the majority of novel viral sharing, and are likely to share viruses along evolutionary pathways that will facilitate future emergence in humans. Surprisingly, we find that this ecological transition may already be underway, and holding warming under 2 °C within the century will not reduce future viral sharing. Our findings highlight an urgent need to pair viral surveillance and discovery efforts with biodiversity surveys tracking species’ range shifts, especially in tropical regions that harbor the most zoonoses and are experiencing rapid warming.
Fourth Dose of BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting
A fourth dose of the BNT162b2 vaccine was effective in reducing the short-term risk of Covid-19–related outcomes among persons who had received a third dose at least 4 months earlier.
April 27, 2022
Alterations in SARS-CoV-2 Omicron and Delta peptides presentation by HLA molecules
Specifically, we predicted a dramatical decline in binding affinity of HLA-DRB1*03:01 and this peptide both because of the Omicron BA.1 mutations (N211 deletion, L212I substitution and EPE 212-214 insertion) and the Omicron BA.2 mutations (V213G substitution). The computational prediction was experimentally validated by ELISA with the use of corresponding thioredoxin-fused peptides and recombinant HLA-DR molecules. Another finding was the significant reduction in the number of tightly binding Spike peptides for HLA-B*07:02 HLA class I allele (both for Omicron and Delta variants). Overall, the majority of HLA alleles and haplotypes was not significantly affected by the mutations, suggesting the maintenance of effective T-cell immunity against the Omicron and Delta variants. Finally, we introduced the Omicron variant to T-CoV portal and added the functionality of haplotype-level analysis to it.
The impact of the COVID-19 pandemic on adolescent mental health: a natural experiment
Had the COVID-19 pandemic not occurred, we estimate that there would be 6% fewer adolescents with high depressive symptoms. No effect of exposure to the pandemic on externalizing difficulties was found. Exploratory analyses to examine subgroup differences in impacts suggest that the negative impact of the COVID-19 pandemic on adolescent mental health may have been greater for females than males. Given the widespread concern over rising adolescent mental health difficulties prior to the pandemic, this paper quantifies the additional impacts of the pandemic. A properly resourced, multi-level, multi-sector public health approach for improving adolescent mental health is necessary.
SBQ-LC (version 1.0) is a comprehensive patient reported outcome instrument developed using modern psychometric methods. It measures symptoms of long covid important to people with lived experience of the condition and may be used to evaluate the impact of interventions and inform best practice in clinical management.
The COVID-19 Pandemic Rages on for People Who Are Immunocompromised
Janet Handal, who has taken immunosuppressive drugs since her 2010 kidney transplant, hasn’t exactly been impressed by public health messaging about COVID-19.
Within a population of hospitalized patients with severe/critical breakthrough COVID-19, a recent fourth dose was associated with significant protection against mechanical ventilation or death, compared to fully vaccinated single-boosted individuals.
Public health impact of covid-19 vaccines in the US: observational study
In total, 30 643 878 cases of covid-19 and 439 682 deaths associated with covid-19 occurred over 132 791 county weeks. A 10% improvement in vaccination coverage was associated with an 8% (95% confidence interval 8% to 9%) reduction in mortality rates and a 7% (6% to 8%) reduction in incidence. Higher vaccination coverage levels were associated with reduced mortality and incidence rates during the eras of alpha and delta variant predominance.
The benefits of large scale covid-19 vaccination
The findings of this study also make clear that many more lives could have been saved, and will be saved, by encouraging people to keep up to date with vaccination in the face of waning immunity and new SARS-CoV-2 variants and by achieving even higher population coverage. How many lives is a matter for others to explore. Meanwhile, this new study is another confidence booster for covid-19 vaccines.
Despite the stunning speed with which highly effective and safe vaccines have been developed, increasingly transmissible variants are emerging. Using surveillance data from Italy (November 2021-March 2022), during the epidemic phase characterized by the predominance of the Omicron variant, vaccination with additional/booster dose significantly reduces the risk at all ages for hospitalization (relative risk (RR): 0.16; 95% confidence interval (CI): 0.13-0.19), admission to ICU (RR: 0.08; 95% CI: 0.06-0.09) and death (RR: 0.13; 95% CI: 0.10-0.16). Results support the importance of receiving a third dose of mRNA COVID-19 vaccine.
Emerging SARS-CoV-2 variants continue to cause waves of new infections globally. Developing effective antivirals against SARS-CoV-2 and its variants is an urgent task. The main protease (Mpro) of SARS-CoV-2 is an attractive drug target because of its central role in viral replication and its conservation among variants. We herein report a series of potent α-ketoamide-containing Mpro inhibitors obtained using the Ugi four-component reaction. The prioritized compound, Y180, showed an IC50 of 8.1 nM against SARS-CoV-2 Mpro and had oral bioavailability of 92.9%, 31.9% and 85.7% in mice, rats and dogs, respectively. Y180 protected against wild-type SARS-CoV-2, B.1.1.7 (Alpha), B.1.617.1 (Kappa) and P.3 (Theta), with EC50 of 11.4, 20.3, 34.4 and 23.7 nM, respectively. Oral treatment with Y180 displayed a remarkable antiviral potency and substantially ameliorated the virus-induced tissue damage in both nasal turbinate and lung of B.1.1.7-infected K18-human ACE2 (K18-hACE2) transgenic mice. Therapeutic treatment with Y180 improved the survival of mice from 0 to 44.4% (P = 0.0086) upon B.1.617.1 infection in the lethal infection model. Importantly, Y180 was also highly effective against the B.1.1.529 (Omicron) variant both in vitro and in vivo. Overall, our study provides a promising lead compound for oral drug development against SARS-CoV-2.
April 26, 2022
As of February 2022, approximately 75% of children and adolescents had serologic evidence of previous infection with SARS-CoV-2, with approximately one third becoming newly seropositive since December 2021. The greatest increases in seroprevalence during September 2021–February 2022, occurred in the age groups with the lowest vaccination coverage; the proportion of the U.S. population fully vaccinated by April 2022 increased with age (5–11, 28%; 12–17, 59%; 18–49, 69%; 50–64, 80%; and ≥65 years, 90%).*** Lower seroprevalence among adults aged ≥65 years, who are at greater risk for severe illness from COVID-19, might also be related to the increased use of additional precautions with increasing age.
These findings illustrate a high infection rate for the Omicron variant, especially among children. Seropositivity for anti-N antibodies should not be interpreted as protection from future infection. Vaccination remains the safest strategy for preventing complications from SARS-CoV-2 infection, including hospitalization among children and adults (4,5). COVID-19 vaccination following infection provides additional protection against severe disease and hospitalization (6). Staying up to date††† with vaccination is recommended for all eligible persons, including those with previous SARS-CoV-2 infection.
In this cohort study of 40.7 million US commercially insured adults with acute clinical conditions, those with an initial telehealth encounter, compared with an in-person encounter, had higher odds for any follow-up encounter, an emergency department encounter, and in-patient admissions. For people with chronic conditions, the odds were lower for those with an initial telehealth encounter.
Excess all-cause mortality across counties in the United States, March 2020 to December 2021
An estimated 936,911 excess deaths occurred during 2020 and 2021, of which 171,168 were not assigned to Covid-19 on death certificates. In the Far West, Great Lakes, Mideast, and New England, there was a substantial urban mortality disadvantage in 2020, which was reversed in 2021 to yield a rural mortality disadvantage. In the Southeast, Southwest, Rocky Mountain, and Plains regions, there was a rural mortality disadvantage in 2020, which was exacerbated in 2021. The proportion of excess deaths assigned to Covid-19 was lower in 2020 (76.3%) than in 2021 (87.0%), suggesting fewer Covid-19 deaths went unassigned later in the pandemic. However, in rural areas and in the Southeast and Southwest many excess deaths were still not assigned to Covid-19 during 2021.
Diagnosis and management of covid-19 in pregnancy
Pregnant women with covid-19 are at greater risk of severe disease than their non-pregnant peers, and yet they are frequently denied investigations or treatments because of unfounded concerns about risk to the fetus. The basic principles of diagnosing and managing covid-19 are the same as for non-pregnant patients, and a multidisciplinary, expert team approach is essential to ensure optimal care. During pregnancy, treatment with corticosteroids should be modified to use non-fluorinated glucocorticoids. Il-6 inhibitors and monoclonal antibodies, together with specific antiviral therapies, may also be considered. Prophylaxis against venous thromboembolism is important. Women may require respiratory support with oxygen, non-invasive ventilation, ventilation in a prone position (either awake or during invasive ventilation), intubation and ventilation, and extracorporeal membrane oxygenation (ECMO). Pregnancy is not a contraindication for any of these supportive therapies, and the criteria for providing them are the same as in the general population. Decisions regarding timing, place, and mode of delivery should be taken with a multidisciplinary team including obstetricians, physicians, anesthetists, and intensivists experienced in the care of covid-19 in pregnancy. Ideally these decisions should take place in consultation with centers that have experience and expertise in all these specialties.
Initiation of NM/R treatment on Day 0 in a 71-year-old vaccinated and boosted male resulted in rapid resolution of COVID-19 symptoms followed one week later by the development of typical cold symptoms. SARS-CoV-2 viral load fluctuated in parallel with symptoms, with two distinct peaks on Day 1 and Day 9 of illness. No other respiratory pathogens were identified. Viral samples demonstrated sequence identity for the omicron subvariant BA.1 on Days 1, 7, and 11. Our findings suggest that viral replication and COVID-19 symptoms may recur after very early treatment with NM/R before natural immunity is sufficient to fully clear SARS-CoV-2.
COVID-19 Vaccine Effectiveness in Youth Varies by Age, Variant
Two vaccine doses were 31% effective against symptomatic or asymptomatic Omicron variant infection among children aged 5 to 11 years and 59% effective among adolescents aged 12 to 15 years. In contrast, 2 doses provided 87% protection against Delta variant infection among adolescents. Still, the authors recommended that all children and adolescents should receive COVID-19 vaccines as recommended, as they reduce the risk of infection even with the Omicron variant. The study also revealed differences in the variants’ effects among unvaccinated youth. About half of unvaccinated children and adolescents with Omicron infections were asymptomatic compared with 34% of those with Delta variant infections. Omicron symptoms lasted 3.4 fewer days and resulted in fewer missed school days than infections with the Delta variant. Vaccination reduced the time children infected with Omicron spent in bed by about a half-day.
White Individuals Experience Less COVID-19–Related Discrimination
Compared with White individuals, all other major racial and ethnic groups in the US experience more COVID-19 discrimination, according to a study coauthored by researchers from the National Institute on Minority Health and Health Disparities. Respondents who identified as Asian, irrespective of national origin, and American Indian or Alaska Native individuals were most likely to experience such discrimination. The findings also suggest that COVID-19 discrimination against Asian individuals has increased over the course of the pandemic.
April 25, 2022
Oral Antiviral Medications for COVID-19
Two new antiviral medications, ritonavir-boosted nirmatrelvir (Paxlovid, ie, nirmatrelvir-ritonavir) and molnupiravir (Lagevrio), are currently available in the US under emergency use authorization. These 2 drugs are authorized for treatment of patients with mild to moderate COVID-19 who are not currently hospitalized but are at high risk of developing severe disease. Nirmatrelvir-ritonavir and molnupiravir are approved for use only within 5 days of onset of COVID-19 symptoms.
Using simple mathematical modelling, we have shown that, although risk associated with avoiding vaccination during a virulent pandemic accrues chiefly to those who are unvaccinated, the choice of some individuals to refuse vaccination is likely to affect the health and safety of vaccinated people in a manner disproportionate to the fraction of unvaccinated people in the population. Risk among unvaccinated people cannot be considered self-regarding, and considerations around equity and justice for people who do choose to be vaccinated, as well as those who choose not to be, need to be considered in the formulation of vaccination policy. It is unlikely that SARS-CoV-2 will be eliminated, and our findings will likely be relevant to future seasonal SARS-CoV-2 epidemics or in the face of emerging variants.
This study demonstrates a substantial reduction in hospitalizations and deaths due to Covid-19 conferred by a second-booster in Israeli adults aged 60 years and over.
Two-dose vaccination induced robust anti-spike antibodies and neutralization titers (NTs) against the ancestral strain WK-521, whereas NTs against VOCs were significantly lower. Within 93–247 days of the second vaccine dose, NTs against Omicron were completely abolished in up to 80% of individuals in the vaccinee panel. Booster dose induced a robust increase in anti-spike antibodies and NTs against the WK-521, Delta, and Omicron variants. There were no significant differences in the neutralization ability of sera from boosted individuals among the Omicron subvariants BA.1, BA.1.1, and BA.2. Boosting increased the breadth of humoral immunity and
April 24, 2022
Neutralization of SARS-CoV-2 Omicron Sub-lineages BA.1, BA.1.1, and BA.2
Recent reports of SARS-CoV-2 Omicron variant sub-lineages, BA.1, BA.1.1, and BA.2, have reignited concern over potential escape from vaccine- and infection-induced immunity. We examine the sensitivity of these sub-lineages and other major variants to neutralizing antibodies from mRNA-vaccinated and boosted individuals, as well as recovered COVID-19 patients, including those infected with Omicron. We find that all Omicron sub-lineages, especially BA.1 and BA.1.1, exhibit substantial immune escape that is largely overcome by mRNA vaccine booster doses. While Omicron BA.1.1 escapes almost completely from neutralization by early-pandemic COVID-19 patient sera and to a lesser extent from sera of Delta infected patients, BA.1.1 is sensitive to Omicron-infected patient sera. Critically, all Omicron sub-lineages, including BA.2, are comparably neutralized by Omicron patient sera. These results highlight the importance of booster vaccine doses for protection against all Omicron variants, and provide insight into the immunity from natural infection against Omicron sub-lineages.
April 23, 2022
Our results suggest that a homologous or heterologous booster dose for individuals with a complete primary vaccination schedule with CoronaVac provides a high level of protection against COVID-19, including severe disease and death. Heterologous boosters showed higher vaccine effectiveness than a homologous booster for all outcomes, providing additional support for a mix-and-match approach.
The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials.
April 22, 2022
Three doses of BNT162b2 conferred high protection against hospital and emergency department admission due to both the delta and omicron variants in the first 3 months after vaccination. However, 3 months after receipt of a third dose, waning was apparent against SARS-CoV-2 outcomes due to the omicron variant, including hospital admission. Additional doses of current, adapted, or novel COVD-19 vaccines might be needed to maintain high levels of protection against subsequent waves of SARS-CoV-2 caused by the omicron variant or future variants with similar escape potential.
Provisional Mortality Data — United States, 2021
The overall age-adjusted death rate increased by 0.7% in 2021 from 2020. Overall death rates were highest among non-Hispanic American Indian or Alaskan Native and non-Hispanic Black or African American populations. For a second year, COVID-19 was the third leading cause of death after heart disease and cancer.
Provisional COVID-19 Age-Adjusted Death Rates, by Race and Ethnicity — United States, 2020–2021
From 2020 to 2021, disparities in AADR ratios from COVID-19 decreased significantly by 14.0%–40.2% for most racial and ethnic groups, including non-Hispanic White persons, who accounted for 59.6%–65.2% of all decedents; and increased nonsignificantly (7.2%) for non-Hispanic Native Hawaiian and other Pacific Islander persons (0.2%–0.3% of all decedents) compared with non-Hispanic multiracial persons.
The findings can inform strategies to increase booster dose vaccinations and effective messaging. COVID-19 vaccinations significantly lower the risk of serious illness from COVID-19 in pregnant individuals, and data indicate potential benefits to the developing fetus. Thus, continued focus to improve vaccinations with booster doses in this population, especially among those with lower vaccination coverage, such as individuals of Black or Hispanic race and ethnicity, is critical.
This cohort study of 49 993 participants in 11 longitudinal studies found that mental health has deteriorated from before the start of the COVID-19 pandemic, and this deterioration was sustained across the first year of the pandemic. Deterioration in mental health varied by sociodemographic factors, namely age, sex, and education, and did not recover when social restrictions were eased.
COVID-19 Vaccination and Estimated Public Health Impact in California
n this modeling study using data from the California Department of Public Health, COVID-19 vaccination was estimated to have prevented more than 1.5 million COVID-19 cases, 72 000 hospitalizations, and 19 000 deaths during the first 10 months of vaccination, through October 16, 2021.
In this cohort study of 25 million working-age adults in California, differences in the distribution of education and occupation across racial and ethnic groups were associated with racial and ethnic inequities in COVID-19 mortality, particularly for Latinx adults. If every working-age Californian had the COVID-19 mortality risk associated with the lowest-risk educational and occupational position, there would have been an estimated 8441 (43%) fewer deaths in this population.
In this decision analytical model study, for a month with transmission intensity similar to that of May 2021, a monoclonal antibody PEP program reaching 50% of exposed, unvaccinated household members aged 50 years and older was estimated to avert 528 hospitalizations and 84 deaths in a low-transmission scenario and 1404 hospitalizations and 223 deaths in a high-transmission scenario. The program was also estimated to be cost saving to payers in the high-transmission scenario as a result of averted hospitalizations.
Assessment of T-cell Reactivity to the SARS-CoV-2 Omicron Variant by Immunized Individuals
In this cohort study among 61 individuals who had been vaccinated against COVID-19, cellular responses to the mutated regions of the Omicron spike protein were detected in 80% of participants. The mutations were associated with significantly reduced T-cell recognition compared with the vaccine strain, while reactivity to the whole spike protein was present in 100% of participants, and the proportion of remaining immunity to SARS-CoV-2 was estimated to be 87%.
To our knowledge, this is one of the first studies to evaluate the association of COVID-19 vaccination status with IVF-fresh embryo transfer cycles (including a high proportion of standard insemination cycles). We found no evidence to suggest that COVID-19 vaccination negatively affects cycle stimulation characteristics, embryological variables, or clinical outcomes in IVF. Current and emerging scientific evidence continues to support that COVID-19 vaccination is safe and effective and has no impact on fertility. The results of this study can be used to provide reassuring data to patients planning on pregnancy considering COVID-19 vaccination.
In an exploratory trial treating “long COVID” with the CCR5-binding antibody leronlimab, we observed significantly increased blood cell surface CCR5 in treated symptomatic responders but not in nonresponders or placebo-treated participants. These findings suggest an unexpected mechanism of abnormal immune downmodulation in some persons that is normalized by leronlimab.
These early national data suggest that omicron is associated with a two-thirds reduction in the risk of COVID-19 hospitalisation compared with delta. Although offering the greatest protection against delta, the booster dose of vaccination offers substantial additional protection against the risk of symptomatic COVID-19 for omicron compared with 25 weeks or more after the second vaccine dose.
We found a significantly lower risk of hospitalisation with omicron infection compared with delta infection among both vaccinated and unvaccinated individuals, suggesting an inherent reduced severity of omicron. Our results could guide modelling of the effect of the ongoing global omicron wave and thus health-care system preparedness.
April 21, 2022
Brain changes after COVID-19 — how concerned should we be?
Analysis of brain images taken before and after infection with SARS-CoV-2 suggests that even mild COVID-19 is associated with brain structure alterations and cognitive impairment. However, the clinical implications for individuals are unclear and further studies are needed to assess the generalizability of the findings and whether the effects are long-lasting.
Changes in mental health measures during the first 15 months of the COVID-19 pandemic were small. More stringent COVID-19 policies were associated with poorer mental health. Elimination strategies minimised transmission and deaths, while restricting mental health effects.
Increased Memory B Cell Potency and Breadth After a SARS-CoV-2 mRNA Boost
We find that the 3rd dose is accompanied by an increase in, and evolution of, anti-receptor binding domain-specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the 2nd dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared to antibodies obtained after the 2nd dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells that differed from the persisting clones in targeting more conserved regions of the RBD. Overall, more than 50% of the analyzed neutralizing antibodies in the memory compartment after a 3rd mRNA vaccine dose neutralized Omicron. Thus, individuals receiving 3 doses of an mRNA vaccine, have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of clearing even diversified variants such as Omicron. These data help explain why a 3rd dose of a vaccine that was not specifically designed to protect against variants is effective against variant-induced serious disease.
April 20, 2022
Among both age groups, VE against COVID-19-related hospitalization 14-30 days since vaccination with two or three doses was 94.8% or above for the Alpha and Delta variants, whereas among the youngest age group, VE estimates against the Omicron variant after two and three doses were 62.4% (95% CI: 46.3; 73.6) and 89.8% (95% CI: 87.9; 91.3), respectively. Conclusions Two vaccine doses provided high protection against SARS-CoV-2 infection and COVID-19-related hospitalization with the Alpha and Delta variants with protection waning over time. Two vaccine doses provided only limited protection against SARS-CoV-2 infection and COVID-19-related hospitalization with the Omicron variant. The third vaccine dose substantially increased the protection against Delta and Omicron.
Rates of COVID-19 Among Unvaccinated Adults With Prior COVID-19
Among 121 615 patients with more than 10 million days of follow-up, unvaccinated individuals with prior symptomatic COVID-19 had 85% lower risk of acquiring COVID-19 than unvaccinated individuals without prior COVID-19. Prior studies investigating protection against SARS-CoV-2 reinfection found similar results, with protection associated with natural immunity ranging from 80.5% to 100%. This level of protection is similar to that reported for mRNA vaccines. The findings that patients with prior COVID-19 had 88% protection against hospitalization for COVID-19 and 83% protection against COVID-19 not requiring hospitalization suggest that natural immunity was associated with similar protection against mild and severe disease. mRNA vaccines are associated with similar prolonged protection from severe COVID-19 as found in our study, although vaccine-associated protection from mild COVID-19 has been shown to wane at 6 months.
Intramuscular AZD7442 (Tixagevimab–Cilgavimab) for Prevention of Covid-19
A single dose of AZD7442 had efficacy for the prevention of Covid-19, without evident safety concerns.
The Evolution and Biology of SARS-CoV-2 Variants
Currently, SARS-CoV-2 has proven itself to be a dangerous new human respiratory pathogen with an unpredictable evolutionary capacity, leading to a risk of future variants too great not to ensure all regions of the world are screened by viral genome sequencing, protected through available and affordable vaccines, and have non-punitive strategies in place for detecting and responding to novel variants of concern.
April 19, 2022
During the period of Omicron predominance (December 19, 2021–February 28, 2022), COVID-19–associated hospitalization rates in children aged 5–11 years were approximately twice as high among unvaccinated as among vaccinated children. Non-Hispanic Black children represented the largest group of unvaccinated children. Thirty percent of hospitalized children had no underlying medical conditions, and 19% were admitted to an intensive care unit. Children with diabetes and obesity were more likely to experience severe COVID-19.
We found that in most individuals, resting heart rate (RHR) increased with respect to their individual baseline after vaccination, peaked on day 2, and returned to normal by day 6. This increase in RHR was greater than one standard deviation above individuals’ normal daily pattern in 47% of participants after their second vaccine dose. Consistent with other reports of subjective reactogenicity following vaccination, we measured a significantly stronger effect after the second dose relative to the first, except those who previously tested positive to COVID-19, and a more pronounced increase for individuals who received the Moderna vaccine. Females, after the first dose only, and those aged <40 years, also experienced a greater objective response after adjusting for possible confounding factors. These early findings show that it is possible to detect subtle, but important changes from an individual’s normal as objective evidence of reactogenicity, which, with further work, could prove useful as a surrogate for vaccine-induced immune response.
Identification of Drug Interaction Adverse Events in Patients With COVID-19
The DDIs identified in this systematic review involved 46 different drugs, with 575 DDIs for 58 drug pairs (305 associated with at least 1 adverse drug reaction) reported. Drug interaction checkers could have identified such events, including severe and life-threatening ones.
Consumer-grade wearables are needed to track disease, especially in the ongoing pandemic, as they can monitor patients in real time. We show that decomposing heart rate from low-cost wearable technologies into signals from different systems can give a multidimensional description of physiological changes due to COVID-19 infection. We find that the separate physiological features of basal heart rate, heart rate response to physical activity, circadian variation in heart rate, and autocorrelation of heart rate are significantly altered and can classify symptomatic versus healthy periods. Increased heart rate and autocorrelation begin at symptom onset, while the heart rate response to activity increases soon after symptom onset and increases more in individuals exhibiting cough. Symptom onset is associated with a blunting of circadian variation in heart rate, as measured by the uncertainty in the phase estimate. This work establishes an innovative data analytic approach to monitor disease progression remotely using consumer-grade wearables.
Pan-coronavirus vaccine pipeline takes form
As debates over additional booster shots for COVID-19 intensify, many public health researchers are looking to the influenza model of vaccination as a guide for how to handle the lasting threat of SARS-CoV-2. That could mean annual shots, as is routine today with seasonal flu prophylaxis. But just as scientists have long sought a universal flu jab that can provide lasting protection against multiple subtypes of that respiratory virus, so too the field is on the hunt for pan-coronavirus vaccines that can ward off future variants of SARS-CoV-2 and preempt the next pandemic.
April 18, 2022
Previous exposure to SARS-CoV-2 decreased the risk and severity of subsequent COVID-19 infection, even against newly emerging variants. Protection is further enhanced by one or two doses of SCB-2019.
A 3rd vaccination significantly improved neutralization capacity per antibody. Conclusions and Relevance The primary schedule for immunocompromised patients with hematologic malignancies should be supplemented with a delayed 3rd vaccination. B cell lymphoma patients and allogeneic HCT recipients need to be revaccinated after treatment or transplantation.
SARS-CoV-2 Omicron variants BA.1 and BA.2 seem to show reduced clinical severity. We classified 172 COVID-19 Omicron patient admissions. 66.2% of patients were admitted with primary or admission-contributing COVID-19. We therefore must be careful to base healthcare and public health decisions on the total number of hospitalized COVID-19 patients alone.
We found that AEs after the BNT162b2 mRNA vaccine booster dose were generally mild and usually did not require medical care. The proportion of self-reported AEs that occurred in our study was similar or lower than that after the administration of the second vaccine dose in several previous studies. A study by Menni et al found a similar proportion of systemic reactions among older individuals after the second vaccine dose as after the third dose in our study (16.4% vs 16.6%). The proportion of female respondents who reported systemic AEs was greater than the proportion of male respondents, with higher proportions among participants in the younger age group (60-69 years) than in the older age groups. Similar results were reported in previous studies after administration of the second vaccine dose.
April 16, 2022
Cracks in the foundation: how COVID-19 showed our failures
In 1963, James Baldwin, one of the USA's greatest essayists, published The Fire Next Time. The book's title comes from a slave song—”God gave Noah the rainbow sign/No more water but the fire next time”. Baldwin's words sounded a warning that the USA needed to confront its racial hierarchy by embracing racial equality or doom its future. Sandro Galea's book, The Contagion Next Time, is titled in a homage to Baldwin and it also sounds a warning. Galea's central argument is that vulnerability to COVID-19 lies with a societal failure to recognise that the foundation of health rests on a healthy everyday life and not simply in the provision of health care. He ponders why this key lesson is not at the centre of pandemic discourse, which instead focuses on vaccination and treatment. In often lyrical prose, Galea roams across history, culture, literature, moral values, economics, politics, and personal pandemic experience. Although situated in a global context, the book's focus is the USA. Galea considers especially the enduring impacts of racism on health and the centrality of structural racism to understanding the USA.
To mask, or not to mask, Alice and Bob’s dating dilemma
Face masking in current COVID-19 pandemic seems to be a deceivingly simple decision-making problem due to its multifaceted nature. Questions arising from masking span biomedicine, epidemiology, physics, and human behaviors. While science has shown masks work generally, human behaviors (particularly under influences of politics) complicate the problem significantly given science generally assumes rationality and our minds are not always rational and/or honest. Minding minds, a legitimate concern, can also make masking legitimately confusing. To disentangle the potential confusions, particularly, the ramifications of irrationality and dishonesty, here we resort to evolutionary game theory.
April 15, 2022
Are new Omicron subvariants a threat? Here's how scientists are keeping watch
In South Africa, a network of researchers are studying whether new lineages BA.4 and BA.5 escape immunity from COVID-19 vaccines and prior infections.
April 14, 2022
Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19
Treatment of symptomatic Covid-19 with nirmatrelvir plus ritonavir resulted in a risk of progression to severe Covid-19 that was 89% lower than the risk with placebo, without evident safety concerns.
In this cohort study of 263 697 fully vaccinated US Department of Veterans Affairs patients, psychiatric disorder diagnoses were associated with increased incidence of SARS-CoV-2 breakthrough infection after vaccination.
Two vaccine doses were found to be highly effective against both SARS-CoV-2 infection and severe COVID-19 outcomes in patients with rheumatoid arthritis, ankylosing spondylitis, psoriasis, and inflammatory bowel disease during the study period. Research is needed to determine the durability of effectiveness of three doses over time, particularly against emerging variants.
Surveillance of Safety of 3 Doses of COVID-19 mRNA Vaccination Using Electronic Health Records
This cohort study of electronic health record data for 47 999 individuals receiving 3-dose mRNA COVID-19 vaccines found no significant increase in the reporting of severe adverse events (ie, anaphylaxis, cerebral venous sinus thrombosis, myocarditis, and pericarditis) after the third vaccine dose compared with before vaccination and after prior doses. Significantly increased reporting was found for low-severity adverse events (ie, fatigue, lymphadenopathy, nausea, and headache).
April 13, 2022
Fourth Dose of BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting
A fourth dose of the BNT162b2 vaccine was effective in reducing the short-term risk of Covid-19–related outcomes among persons who had received a third dose at least 4 months earlier.
Covid-19 Boosters — Where from Here?
It is now incumbent on the CDC to determine who most benefits from booster dosing and to educate the public about the limits of mucosal vaccines. Otherwise, a zero-tolerance strategy for mild or asymptomatic infection, which can be implemented only with frequent booster doses, will continue to mislead the public about what Covid-19 vaccines can and cannot do.
Human primary Omicron BA.1 and BA.2 infections result in sub-lineage-specific neutralization
The recently emerged Omicron variant is the most antigenically distinct SARS-CoV-2 variant of concern to date. As the heavily mutated spike protein enables escape from neutralizing antibodies, we studied the neutralizing activities of sera after Omicron BA.1 and BA.2 infections of naïve and vaccinated individuals. We show that primary BA.1 infections yielded reduced neutralizing antibody titers against wildtype (WT), Delta, and BA.2, while serum samples from individuals after BA.2 infection showed no cross-neutralization against the other variants. Fully vaccinated individuals were still able to neutralize both Omicron sub-lineages up to three months after vaccination, and Omicron-breakthrough infections showed equal cross-neutralizing activities against WT, Delta, BA.1, and BA.2. Our data demonstrate that Omicron variants are able to enhance cross-neutralizing antibodies in pre-immune individuals. Primary infections with one of the Omicron sub-lineages, however, induced variant-specific neutralizing antibodies. In particular, BA.2 infections generated a sub-lineage-specific response, emphasizing its antigenic distance.
April 12, 2022
Among persons with previous infection, COVID-19 mRNA vaccination provided protection against subsequent COVID-19–associated hospitalization. Estimated vaccine effectiveness against reinfection leading to hospitalization during the Omicron-predominant period was approximately 35% after dose 2, and 68% after a booster dose. To prevent COVID-19–associated hospitalization, all eligible persons should stay up to date with vaccination, including those with previous SARS-CoV-2 infection.
April 11, 2022
Prevalence, Characteristics, and Outcomes of COVID-19–Associated Acute Myocarditis
AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.
Coronavirus disease 2019 (COVID-19) resulted in a global pandemic and has overwhelmed health care systems worldwide. In this scientific statement, we describe the epidemiology, pathophysiology, clinical presentations, treatment, and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and multisystem inflammatory syndrome in children and young adults with a focus on cardiovascular manifestations and complications. We review current knowledge about the health consequences of this illness in children and young adults with congenital and acquired heart disease, the public health burden and health disparities of this infection in these populations, and vaccine-associated myocarditis.
The overall risk of myopericarditis after receiving a COVID-19 vaccine is low. However, younger males have an increased incidence of myopericarditis, particularly after receiving mRNA vaccines. Nevertheless, the risks of such rare adverse events should be balanced against the risks of COVID-19 infection (including myopericarditis).
Understanding COVID-19 through genome-wide association studies
Defining the most appropriate phenotypes in genome-wide association studies of COVID-19 is challenging, and two new publications demonstrate how case-control definitions critically determine outcomes and downstream clinical utility of findings.
In the region of olfactory bulb and olfactory tract, COVID-19 infection was associated with axon pathology and microvasculopathy, particularly in patients with smell alterations; the olfactory pathology did not result from direct viral injury and may be associated with local inflammation.
In the region of olfactory bulb and olfactory tract, COVID-19 infection was associated with axon pathology and microvasculopathy, particularly in patients with smell alterations; the olfactory pathology did not result from direct viral injury and may be associated with local inflammation.
April 8, 2022
Among persons aged ≥60 years in Hong Kong, 49% had received ≥2 doses of a COVID-19 vaccine, and vaccination coverage declined with age. During January–March 2022, reported COVID-19–associated deaths rose rapidly in Hong Kong. Among these deaths, 96% occurred in persons aged ≥60 years; within this age group, the risk for death was 20 times lower among those who were fully vaccinated compared with those who were unvaccinated.
Vaccination protects against infection with SARS-CoV-2 (the virus that causes COVID-19) and related hospitalizations, and surviving a previous infection protects against B.1.1.7 (Alpha) and B.1.617.2 (Delta) variant reinfections. Since the SARS-CoV-2 B.1.1.529 (Omicron) variant became predominant in the United States in late December 2021, reported reinfections have increased. Early reinfections (those occurring within 90 days of previous infection) are not well understood. Because some persons have prolonged detection of viral RNA after infection, repeat positive nucleic acid amplification test (NAAT) results within 90 days could reflect prolonged shedding from earlier infection, presenting technical challenges to documenting and characterizing early reinfections. This report describes 10 patients from four states, with whole genome sequencing (WGS)–confirmed Omicron variant infections within 90 days of a previous Delta infection. This activity was reviewed by CDC, approved by respective institutional review boards, and was conducted consistent with applicable federal law and CDC policy.
In this cohort study of a nationwide database of electronic health records of 636 465 vaccinated patients, the 45 253 vaccinated patients with cancer had significantly higher risk for breakthrough SARS-CoV-2 infections than propensity score–matched patients without cancer, with marked heterogeneity among 12 common cancers, including solid tumors and hematologic cancers, most common in patients with active cancer within the past year. Breakthrough infections in patients with cancer were associated with significant and substantial risks for hospitalizations and mortality.
Systemic Corticosteroid Use for COVID-19 in US Outpatient Settings From April 2020 to August 2021
In June 2020, preliminary results for the Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial conducted in the UK indicated benefit from dexamethasone in severely ill hospitalized patients with COVID-19 but potential harm in those not requiring oxygen. In October 2020, the National Institutes of Health (NIH) issued COVID-19 treatment guidelines advising against systemic corticosteroid use in patients with mild to moderate COVID-19. Using 2 large US health care claims databases, we examined systemic corticosteroid use among nonhospitalized patients with COVID-19.
During the first year of the COVID-19 pandemic, 30% of outpatient visits for COVID-19 among Medicare beneficiaries were linked to an antibiotic prescription, 50.7% of which were for azithromycin. Randomized clinical trials demonstrated no benefit of azithromycin in treating COVID-19, and its use for the disease has been linked to antimicrobial resistance. The largest number of visits and highest rates of antibiotic prescribing were observed in the ED, perhaps reflecting acuity of care, and urgent care centers had the highest rate of azithromycin prescribing. Telehealth visits had the second highest antibiotic prescribing rate and were close in volume to office visits, emphasizing the importance of optimizing antibiotic prescribing practices in this setting. Antibiotic prescribing occurred at a higher rate for non-Hispanic White beneficiaries than for those from other racial and ethnic groups. Although described in pediatrics, this racial difference has not been well characterized in older adults and warrants further evaluation because it may indicate more services are being provided to White beneficiaries, even if not indicated.
April 7, 2022
After over a billion of vaccinations with messenger RNA-lipid nanoparticle (mRNA-LNP) based SARS-CoV-2 vaccines, anaphylaxis and other manifestations of hypersensitivity can be considered as very rare adverse events. Although current recommendations include avoiding a second dose in those with first-dose anaphylaxis, the underlying mechanisms are unknown; therefore, the risk of a future reaction cannot be predicted. Given how important new mRNA constructs will be to address the emergence of new viral variants and viruses, there is an urgent need for clinical approaches that would allow a safe repeated immunization of high-risk individuals and for reliable predictive tools of adverse reactions to mRNA vaccines. In many aspects, anaphylaxis symptoms experienced by the affected vaccine recipients resemble those of infusion reactions to nanomedicines. Here we share lessons learned over a decade of nanomedicine research and discuss the current knowledge about several factors that individually or collectively contribute to infusion reactions to nanomedicines. We aim to use this knowledge to inform the SARS-CoV-2 lipid-nanoparticle-based mRNA vaccine field.
Three in ten survivors with COVID-19 developed a subset of symptoms associated with PASC in our cohort. While ethnic minorities, older age, and social disadvantage are associated with worse acute COVID-19 infection and greater risk of death, our study found no association between these factors and PASC.
April 6, 2022
The findings of this study suggest that covid-19 is a risk factor for deep vein thrombosis, pulmonary embolism, and bleeding. These results could impact recommendations on diagnostic and prophylactic strategies against venous thromboembolism after covid-19.
Thromboembolism and bleeding after covid-19
It is now clear from meta-analyses of case series, cohort studies, and self-controlled case series that the risk of venous thromboembolism is increased after SARS-CoV-2 infection. However, two important questions remain: for how long post-infection is the risk increased, and does mild infection also increase risk? In a linked paper, Katsoularis and colleagues (doi:10.1136/bmj-2021-069590) address these questions by applying two complementary study designs to data from several Swedish registries.
Fluvoxamine for Outpatient Management of COVID-19 to Prevent Hospitalization
In this systematic review and bayesian meta-analysis of 3 clinical trials, which accounted for varying prior probabilities coupled with a frequentist sensitivity analysis, there was a high probability (94.1%-98.6%) that fluvoxamine was associated with a reduced risk for hospitalization, with a frequentist risk ratio of 0.75 (95% CI, 0.58-0.97). These findings suggest that fluvoxamine, a widely available and inexpensive treatment for outpatients with COVID-19, was associated with a reduction in hospitalizations.
To our knowledge, this cross-sectional study is the first to examine the association of the FDA’s full approval of the BNT162b2 mRNA COVID-19 vaccine with subsequent US COVID-19 vaccinations. We estimated that approval was significantly associated with an increase in the overall number of vaccines administered; however, this appears to be largely related to an increase in series completions after approval. Our analysis suggests that approval may have been associated with a decrease in the number of first doses administered compared with what would have been expected without approval. Potential limitations of this study include the possibility of spillover effects and the relative shortness of the postintervention period considered.
In this retrospective cohort study of 471 791 rural US veterans with a history of mental health care use, receipt of a video-enabled tablet was associated with increased use of mental health care via video, increased psychotherapy visits (across all modalities), and reduced suicide behavior and ED visits.
Why the WHO took two years to say COVID is airborne
Early in the pandemic, the World Health Organization stated that SARS-CoV-2 was not transmitted through the air. That mistake and the prolonged process of correcting it sowed confusion and raises questions about what will happen in the next pandemic.
FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation
SARS-CoV-2 can cause acute respiratory distress and death in some patients1. Although severe COVID-19 disease is linked to exuberant inflammation, how SARS-CoV-2 triggers inflammation is not understood2. Monocytes and macrophages are sentinel cells that sense invasive infection to form inflammasomes that activate caspase-1 and gasdermin D (GSDMD), leading to inflammatory death (pyroptosis) and release of potent inflammatory mediators3. Here we show that about 6% of blood monocytes in COVID-19 patients are infected with SARS-CoV-2. Monocyte infection depends on uptake of antibody-opsonized virus by Fcγ receptors. Vaccine recipient plasma does not promote antibody-dependent monocyte infection. SARS-CoV-2 begins to replicate in monocytes, but infection is aborted, and infectious virus is not detected in infected monocyte culture supernatants. Instead, infected cells undergo inflammatory cell death (pyroptosis) mediated by activation of NLRP3 and AIM2 inflammasomes, caspase-1 and GSDMD. Moreover, tissue-resident macrophages, but not infected epithelial and endothelial cells, from COVID-19 lung autopsies have activated inflammasomes. These findings taken together suggest that antibody-mediated SARS-CoV-2 uptake by monocytes/macrophages triggers inflammatory cell death that aborts production of infectious virus but causes systemic inflammation that contributes to COVID-19 pathogenesis.
April 5, 2022
These findings suggest that in high-income settings, adults aged 60 years and older who are not fully vaccinated should be given priority to receive REGEN-COV for treating recently diagnosed COVID-19, particularly when supply is limited. It should be noted, however, that clinical trials on the use of REGEN-COV as PEP2 or for treatment3 were conducted before widespread circulation of the SARS-CoV-2 Delta and Omicron variants; therefore, a limitation of this analysis is that the estimated cost-effectiveness may be influenced if the efficacy of REGEN-COV differs by variant. Care must be taken to prevent the availability of monoclonal antibodies from deterring vaccination, which should remain the preferred means of preventing severe COVID-19.
At-home COVID-19 Test Instructions Frequently Misinterpreted
The US Food and Drug Administration (FDA) instructions accompanying at-home SARS-CoV-2 rapid self-tests often confused people in a recent trial reported in JAMA Internal Medicine, causing them to incorrectly decide not to quarantine.
Maternal COVID-19 Vaccine Safe for Infants
A study in Israel found that individuals who received an mRNA COVID-19 vaccine during pregnancy delivered infants with no increased risk for morbidity or mortality compared with infants whose birthing parents weren’t vaccinated.
The apparent increased COVID-19 deaths reported on weekends might confound projections and create a false sense of security on subsequent weekdays. The apparent increased mortality on weekends might be preventable with more consistent clinical care and public health documentation on all days of the week.
Increased Risk of Herpes Zoster in Adults ≥50 Years Old Diagnosed With COVID-19 in the United States
We found that COVID-19 diagnosis in ≥50-year-olds was associated with a significantly increased risk of developing HZ, highlighting the relevance of maintaining HZ vaccination.
April 4, 2022
In this survey study, 3 themes emerged from our analysis. First, translation from evidence to practice guidelines was remarkably complete for interventions supported by aligned national guidelines and high-quality studies. A striking example is the near universal adoption of dexamethasone among patients requiring at least 4 L of supplementary oxygen only 6 to 8 months after the RECOVERY trial demonstrated a survival benefit. The lone exception to this trend was baricitinib; however, new evidence and guidelines were released within 1 week of survey distribution. Practice convergence was also observed when evidence and guidelines aligned against interventions, as seen in the infrequent recommendation of dexamethasone for patients with oxygen saturation greater than 94%, as measured by pulse oximetry. However, clear opportunity for improvement still exists.
Approximately 3% of patients with pneumonia associated with SARS-CoV-2 infection developed new-onset dementia, which was significantly higher than the rate seen with other pneumonias.
April 1, 2022
Data from 40 health care systems participating in a large network found that the risk for cardiac complications was significantly higher after SARS-CoV-2 infection than after mRNA COVID-19 vaccination for both males and females in all age groups. These findings support continued use of recommended mRNA COVID-19 vaccines among all eligible persons aged ≥5 years.
March 31, 2022
The Concept of Classical Herd Immunity May Not Apply to COVID-19
However, SARS-CoV-2, the virus that causes COVID-19, is so different from polio and measles that classical herd immunity may not readily apply to it. Important differences include the phenotypic stability of polio and measles viruses, and their ability to elicit long-term protective immunity, compared to SARS-CoV-2. For these and other reasons, controlling COVID-19 by increasing herd immunity may be an elusive goal.
Protection against the Omicron Variant from Previous SARS-CoV-2 Infection
Overall, in a national database study in Qatar, we found that the effectiveness of previous infection in preventing reinfection with the alpha, beta, and delta variants of SARS-CoV-2 was robust (at approximately 90%), findings that confirmed earlier estimates. Such protection against reinfection with the omicron variant was lower (approximately 60%) but still considerable. In addition, the protection of previous infection against hospitalization or death caused by reinfection appeared to be robust, regardless of variant.
March 30, 2022
Effect of Early Treatment with Ivermectin among Patients with Covid-19
Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19.
March 29, 2022
VE against COVID-19–associated emergency department/urgent care visits was 24% after 1 Jansen dose, 54% after 2 Jansen doses, and 79% after 1 Janssen/1 mRNA dose, compared to 83% after 3 mRNA doses. VE for the same strategies against COVID-19–associated hospitalization was 31%, 67%, 78%, and 90% respectively. All eligible persons should receive recommended COVID-19 booster doses to prevent moderate to severe COVID-19. Adult Janssen primary vaccine recipients should preferentially receive a heterologous mRNA vaccine booster dose ≥2 months later.
CDC Recommends Additional Boosters for Certain Individuals
Following FDA’s regulatory actionexternal icon today, CDC is updating its recommendations to allow certain immunocompromised individuals and people over the age of 50 who received an initial booster dose at least 4 months ago to be eligible for another mRNA booster to increase their protection against severe disease from COVID-19. Separately and in addition, based on newly published data, adults who received a primary vaccine and booster dose of Johnson & Johnson’s Janssen COVID-19 vaccine at least 4 months ago may now receive a second booster dose using an mRNA COVID-19 vaccine.
March 28, 2022
Serum neutralisation of the SARS-CoV-2 omicron sublineage BA.2
Our data indicate that the immune escape from BA.2 is not as severe as from BA.1, suggesting that other viral or host factors are driving the rapid spread of BA.2. Since NAb titres correlate with vaccine effectiveness, our data suggest that currently available vaccines might be more effective against BA.2 than BA.1.
Accelerated identification of disease-causing variants with ultra-rapid nanopore genome sequencing
Whole-genome sequencing (WGS) can identify variants that cause genetic disease, but the time required for sequencing and analysis has been a barrier to its use in acutely ill patients. In the present study, we develop an approach for ultra-rapid nanopore WGS that combines an optimized sample preparation protocol, distributing sequencing over 48 flow cells, near real-time base calling and alignment, accelerated variant calling and fast variant filtration for efficient manual review. Application to two example clinical cases identified a candidate variant in <8 h from sample preparation to variant identification. We show that this framework provides accurate variant calls and efficient prioritization, and accelerates diagnostic clinical genome sequencing twofold compared with previous approaches.
A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic
Here, we identify and characterize a small-molecule compound, N-0385, which exhibits low nanomolar potency and a selectivity index of >10 at inhibiting SARS-CoV-2 infection in human lung cells and in donor-derived colonoids. In Calu-3 cells it inhibits entry of SARS-CoV-2 VOCs, B.1.1.7, B.1.351, P.1 and B.1.617.2. Importantly, in the K18-human ACE2 transgenic mouse model of severe SARS-CoV-2 disease, we found that N-0385 affords a high level of prophylactic and therapeutic benefit following either multiple or even a single administration. This demonstrates that TTSP-mediated proteolytic maturation of spike is critical for SARS-CoV-2 infection in vivo and suggests that N-0385 provides a novel effective early treatment option against COVID-19 and emerging SARS-CoV-2 VOCs.
Will Omicron finally overpower China’s COVID defences?
China’s hard-line approach to eliminating COVID-19 seems to be softening. In his speech, Xi also flagged a more pragmatic strategy, asking that officials limit the economic impact of control measures. In practice, this means that people with asymptomatic cases of COVID-19 are being sent to dedicated isolation centres rather than hospitals, and are monitored for shorter periods than previously required. But some researchers are divided about whether the virus will spread out of control before the government has time to prepare.
March 27, 2022
Boosting with variant-matched or historical mRNA vaccines protects against Omicron infection in mice
The large number of spike substitutions in Omicron lineage variants (BA.1, BA.1.1. and BA.2) could jeopardize the efficacy of SARS-CoV-2 vaccines. We evaluated in mice the protective efficacy of the Moderna mRNA-1273 vaccine against BA.1 before or after boosting. Whereas two doses of mRNA-1273 vaccine induced high levels of neutralizing antibodies against historical WA1/2020 strains, lower levels against BA.1 were associated with breakthrough infection and inflammation in the lung. A primary vaccination series with mRNA-1273.529, an Omicron-matched vaccine, potently neutralized BA.1 but inhibited historical or other SARS-CoV-2 variants less effectively. However, boosting with either mRNA-1273 or mRNA-1273.529 vaccines increased neutralizing titers and protection against BA.1 and BA.2 infection. Nonetheless, the neutralizing antibody titers were higher, and lung viral burden and cytokines were slightly lower in mice boosted with mRNA-1273.529 and challenged with BA.1. Thus, boosting with mRNA-1273 or mRNA-1273.529 enhances protection against Omicron infection with limited differences in efficacy measured.
Throughout the SARS-CoV-2 pandemic, multiple waves of variants of concern have swept across populations, leading to a chain of new and yet more contagious lineages dominating COVID-19 cases. Here, we tracked the remarkably rapid shift from Omicron BA.1 to BA.2 sub-variant dominance in the Swedish population during January-March 2022. By analysis of 174,933 clinical nasopharyngeal swab samples using a custom variant-typing RT-PCR assay, we uncover nearly two-fold higher levels of viral RNA in cases with Omicron BA.2. Importantly, increased viral load in the upper pharynx upon BA.2 infection may provide part of the explanation why Omicron BA.2 is more transmissible and currently outcompetes the BA.1 variant across populations.
The direction of change in disease severity between successively emerging SARS-CoV-2 variants of concern was inconsistent. This heterogeneity in virulence between variants, coupled with independent evolutionary emergence, demonstrates that severity associated with future SARS-CoV-2 variants is inherently unpredictable.
March 25, 2022
Use of At-Home COVID-19 Tests — United States, August 23, 2021–March 12, 2022
A rapid increase in U.S. at-home test use occurred between the SARS-CoV-2 Delta- and Omicron-predominant periods; at-home test use was lower among persons who self-identified as Black, were aged ≥75 years, had lower incomes, and had a high school level education or less. Commonly reported reasons for using at-home tests included exposure concerns and symptoms.
Ultrastructural insight into SARS-CoV-2 entry and budding in human airway epithelium
For all isolates, the virus infected ciliated but not goblet epithelial cells. Key SARS-CoV-2 entry molecules, ACE2 and TMPRSS2, were found to be localised to the plasma membrane including microvilli but excluded from cilia. Consistently, extracellular virions were seen associated with microvilli and the apical plasma membrane but rarely with ciliary membranes. Profiles indicative of viral fusion where tomography showed that the viral membrane was continuous with the apical plasma membrane and the nucleocapsids diluted, compared with unfused virus, demonstrate that the plasma membrane is one site of entry where direct fusion releasing the nucleoprotein-encapsidated genome occurs. Intact intracellular virions were found within ciliated cells in compartments with a single membrane bearing S glycoprotein. Tomography showed concentration of nucleocapsids round the periphery of profiles strongly suggestive of viral budding into these compartments and this may explain how virions gain their S glycoprotein containing envelope.
Our findings support that the outcomes of KT after COVID-19 recovery are excellent with absence of COVID-19 sequelae during follow-up. Additionally, there does not seem to be a need for changes in the induction/immunosuppression regimen based on the severity of COVID-19.
This decision analytical model study used CICT program data from 23 jurisdictions and estimated that CICT programs averted 1.11 to 1.36 million cases and 27 231 to 33 527 hospitalizations over 60 days during the 2020 to 2021 winter peak of the pandemic. The upper estimate assumes that all interviewed cases and monitored contacts complied with isolation and quarantine guidelines, whereas the lower estimate assumes that fractions of interviewed cases and monitored or notified contacts did so.
Among 6076 participants (median age 64 years, interquartile range 55–75) included in this analysis, breakthrough infections due to the Delta variant were observed in 127 participants and in 363 due to the Omicron variant. The incidence rate ratio (IRR) for breakthrough infection with the Delta variant decreased with higher levels of anti-spike IgG yielding an IRR of 0.28 (95% CI 0·15–0·55) when comparing the highest and lowest quintiles of anti-spike IgG. For the Omicron variant, no significant differences in IRR of breakthrough infection between quintiles of anti-spike IgG was observed. Notably, 1 of 127 (0·8%) SARS-CoV-2 Delta variant and 0 of 336 (0%) Omicron variant breakthrough infections resulted in severe COVID-19.
March 24, 2022
Association of SARS-CoV-2 Vaccination During Pregnancy With Pregnancy Outcomes
In this population-based retrospective cohort study that included 157 521 deliveries in Sweden and Norway, SARS-CoV-2 vaccination during pregnancy, compared with no SARS-CoV-2 vaccination during pregnancy, was not significantly associated with risk of preterm birth (adjusted hazard ratio [aHR], 0.98), stillbirth (aHR, 0.86), small for gestational age (adjusted odds ratio [aOR], 0.97), low Apgar score (aOR, 0.97), or neonatal care admission (aOR, 0.97).
COVID-19 mRNA Vaccines During Pregnancy
ARS-CoV-2 infection during pregnancy is associated with increased risk for maternal morbidity and adverse birth outcomes. COVID-19 vaccines are effective for preventing severe disease, including in pregnant populations. Although more than 100 countries recommend COVID-19 vaccination during pregnancy, COVID-19 vaccination in pregnant people has lagged behind that for age-matched, nonpregnant adults. As of February 2022, the US Vaccine Safety Datalink estimated that 68% of pregnant individuals have completed the primary COVID-19 vaccine series.6 Persistent wide disparities in COVID-19 vaccination during pregnancy by race or ethnicity are likely to exacerbate longstanding disparities in maternal morbidity and mortality.
SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing titers against D614G were 4760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (pre-boost), respectively, and 320 and 110 for Omicron. Two weeks after boost, titers against D614G and Omicron increased to 5360 and 2980 for mRNA-1273 boost and 2670 and 1930 for mRNA-Omicron. Similar increases against BA.2 were observed. Following either boost, 70-80% of spike-specific B cells were cross-reactive against WA1 and Omicron. Equivalent control of virus replication in lower airways was observed following Omicron challenge one month after either boost. These data show that mRNA-1273 and mRNA-Omicron elicit comparable immunity and protection shortly after the boost.
Relative Effectiveness of Four Doses Compared to Three Dose of the BNT162b2 Vaccine in Israel
A fourth dose of the BNT162b2 vaccine provided considerable additional protection against both SARS-CoV-2 infection and severe disease relative to three doses of the vaccine. However, effectiveness of the fourth dose against infection wanes sooner than that of the third dose.
Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19
In a cohort study of 112 269 patients with moderate COVID-19, early aspirin use during the first day of hospitalization was associated with lower 28-day in-hospital mortality and pulmonary embolism incidence when compared with patients who did not receive early aspirin.
Second Booster Vaccine and Covid-19 Mortality in Adults 60 to 100 Years Old
This retrospective cohort study included all members of Clalit Health Services, aged 60 to 100, eligible for the second-booster. Mortality due to Covid-19 among participants who received the second-booster was compared with participants who received one booster dose. A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association between the second-booster and death due to Covid-19 while adjusting for demographic factors and coexisting illnesses. A total of 563,465 participants met the eligibility criteria. Of those, 328,597 (58%) received a second-booster dose during the 40-day study period. Death due to Covid-19 occurred in 92 second-booster recipients and in 232 participants who received one booster dose (adjusted hazard ratio 0.22; 95% confidence interval 0.17 to 0.28). This study demonstrates a substantial reduction in Covid-19 mortality by the second-booster in eligible subjects.
March 23, 2022
Correlates of protection via modeling
Establishing correlates of protection (COP) for vaccine preventable infections is an important public health priority. COP are specific, measurable components of a pathogen-specific immune response that are statistically proven to surpass a quantitative threshold required for protection, and they may be identified after natural infection or vaccination. COP are typically validated with symptomatic illness as an endpoint, but they can also be applied to other outcomes, such as asymptomatic infection, severe disease or transmissibility. Validated COP are used as surrogate endpoints in vaccine trials; such surrogate endpoints are useful because they allow rapid ascertainment of vaccine efficacy without having to rely on clinical infection endpoints, which occur in only a fraction of participants.
We show undetectable humoral responses following two vaccine doses in 52% of patients undergoing active anticancer treatment. Moreover, 60% of patients on anti-CD20 therapy had undetectable antibodies following full vaccination within 12 months of receiving their anticancer therapy. However, 70% of individuals with indolent B-cell lymphoma displayed improved antibody responses following booster vaccination. Notably, 63% of all patients displayed antigen-specific T-cell responses, which increased after a third dose irrespective of their cancer treatment status. Our results emphasize the urgency of careful monitoring of COVID-19-specific immune responses to guide vaccination schemes in these vulnerable populations.
All treated individuals displayed elevated antibody levels in their sera, which efficiently neutralized the Delta variant. Sera from Ronapreve recipients did not neutralize BA.1 and weakly inhibited BA.2. Neutralization of BA.1 and BA.2 was detected in 19 and 29 out of 29 Evusheld recipients, respectively. As compared to the Delta variant, neutralizing titers were more markedly decreased against BA.1 (344-fold) than BA.2 (9-fold). We further report 4 breakthrough Omicron infections among the 29 individuals, indicating that antibody treatment did not fully prevent infection. Collectively, BA.1 and BA.2 exhibit noticeable differences in their sensitivity to therapeutic mAbs. Anti-Omicron neutralizing activity of Ronapreve, and to a lesser extent that of Evusheld, is reduced in patients’ sera.
Post-acute sequelae of COVID-19: A metabolic perspective
The SARS-CoV-2 pandemic continues to rage around the world. At the same time, despite strong public health measures and high vaccination rates in some countries, a post-COVID-19 syndrome has emerged which lacks a clear definition, prevalence, or etiology. However, fatigue, dyspnea, brain fog, and lack of smell and/or taste are often characteristic of patients with this syndrome. These are evident more than a month after infection, and are labeled as Post-Acute Sequelae of CoV-2 (PASC) or commonly referred to as long-COVID. Metabolic dysfunction (i.e., obesity, insulin resistance, and diabetes mellitus) is a predisposing risk factor for severe acute COVID-19, and there is emerging evidence that this factor plus a chronic inflammatory state may predispose to PASC. In this article, we explore the potential pathogenic metabolic mechanisms that could underly both severe acute COVID-19 and PASC, and then consider how these might be targeted for future therapeutic approaches.
March 22, 2022
Evaluation of science advice during the COVID-19 pandemic in Sweden
The Swedish response to this pandemic was unique and characterised by a morally, ethically, and scientifically questionable laissez-faire approach, a consequence of structural problems in the society. There was more emphasis on the protection of the “Swedish image” than on saving and protecting lives or on an evidence-based approach. A strategy was never discussed among all relevant parties, and never implemented nor communicated to the public. In addition, there was an unwillingness and incapacity to admit any failures at all governmental levels; or to take any responsibility for the clearly detrimental outcomes for Swedish society. There were even attempts to revise history by changing, or deleting official documents, communication, and websites, and gaslighting the public. The Swedish authorities involved were not self-critical and did not engage in any official and open dialogue and misled the public by withholding correct information and even spreading misleading information. A small group of so-called experts with a narrow disciplinary focus received a disproportionate and unquestioned amount of power in the discussion, nationally and internationally. There was no intellectual/scientific discussion between stakeholders (including independent experts from different disciplines), and the international advice of WHO, ECDC and the scientific community was ignored and/or discredited.
In this bayesian randomized clinical trial that included 1557 patients, antiplatelet therapy with either aspirin or a P2Y12 inhibitor, compared with no antiplatelet therapy, resulted in a 95.7% posterior probability of futility with regard to the odds of improvement in organ support–free days within 21 days.
March 21, 2022
Risks and burdens of incident diabetes in long COVID: a cohort study
In the post-acute phase, we report increased risks and 12-month burdens of incident diabetes and antihyperglycaemic use in people with COVID-19 compared with a contemporary control group of people who were enrolled during the same period and had not contracted SARS-CoV-2, and a historical control group from a pre-pandemic era. Post-acute COVID-19 care should involve identification and management of diabetes.
The intrinsic severity of Omicron BA.2 is not mild as evident by the fatality and severe complications of the uninfected and unvaccinated children.
March 18, 2022
Receiving 2 or 3 doses of an mRNA COVID-19 vaccine was associated with a 90% reduction in risk for COVID-19–associated IMV or death. Protection of 3 mRNA vaccine doses during the period of Omicron predominance was 94%.
In January 2022, unvaccinated adults and those vaccinated with a primary series, but no booster or additional dose, were 12 and three times as likely to be hospitalized, respectively, as were adults who received booster or additional doses. Hospitalization rates among non-Hispanic Black adults increased more than rates in other racial/ethnic groups.
On February 4, 2022, after a systematic review of the evidence, the Advisory Committee on Immunization Practices issued a standard recommendation for use of the Moderna COVID-19 vaccine in persons aged ≥18 years. CDC provided guidance that an 8-week interval between primary series doses of mRNA vaccines might be optimal for some persons.
March 17, 2022
Homologous and Heterologous Covid-19 Booster Vaccinations
Homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier.
Imprinted SARS-CoV-2-specific memory lymphocytes define hybrid immunity
We found that following vaccination, previously infected individuals generated more SARS-CoV-2 RBD-specific memory B cells and variant-neutralizing antibodies and a distinct population of IFN-γ and IL-10-expressing memory SARS-CoV-2 spike-specific CD4+ T cells than previously naive individuals. While additional vaccination could increase humoral memory in previously naive individuals, it did not recapitulate the distinct CD4+ T cell cytokine profile observed in previously infected subjects. Thus, imprinted features of SARS-CoV-2-specific memory lymphocytes define hybrid immunity.
March 16, 2022
Neutralization of the SARS-CoV-2 Omicron BA.1 and BA.2 Variants
Overall, these data show that neutralizing antibody titers against BA.2 were similar to those against BA.1, with median titers against BA.2 that were lower than those against BA.1 by a factor of 1.3 to 1.4. A third dose of the BNT162b2 vaccine was needed for induction of consistent neutralizing antibody titers against either BA.1 or BA.2. Moreover, in vaccinated persons who had presumably been infected with BA.1, robust neutralizing antibody titers against BA.2 developed, which suggests a substantial degree of cross-reactive natural immunity. These findings have important public health implications and suggest that the increasing frequency of BA.2 in the context of the BA.1 surge is probably related to increased transmissibility rather than to enhanced immunologic escape.
Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron
Our data provide evidence that a fourth dose of mRNA vaccine is immunogenic, safe, and somewhat efficacious (primarily against symptomatic disease). A comparison of the initial response to the fourth dose with the peak response to a third dose did not show substantial differences in humoral response or in levels of omicron-specific neutralizing antibodies. Along with previous data showing the superiority of a third dose to a second dose, our results suggest that maximal immunogenicity of mRNA vaccines is achieved after three doses and that antibody levels can be restored by a fourth dose. Furthermore, we observed low vaccine efficacy against infections in health care workers, as well as relatively high viral loads suggesting that those who were infected were infectious. Thus, a fourth vaccination of healthy young health care workers may have only marginal benefits. Older and vulnerable populations were not assessed.
March 15, 2022
During Omicron variant predominance beginning in late December 2021, U.S. infants and children aged 0–4 years were hospitalized at approximately five times the rate of the previous peak during Delta variant predominance. Infants aged <6 months had the highest rates of hospitalization, but indicators of severity (e.g., respiratory support) did not differ by age group.
March 14, 2022
Antigenic evolution will lead to new SARS-CoV-2 variants with unpredictable severity
Viruses evolve to maximize their transmissibility and sometimes this may correlate with higher virulence, for example, if high viral loads promote transmission but also increase severity. If so, pathogens may evolve towards higher virulence. If severity manifests late in infection, only after the typical transmission window, as in SARS-CoV-2, but also influenza virus, HIV, hepatitis C virus and many others, it plays a limited role in viral fitness and may not be selected against. Forecasting virulence evolution is a complex task, and the lower severity of Omicron is hardly a good predictor for future variants. The prospect of future VOCs featuring the potentially disastrous combination of the ability to reinfect due to immune escape along with high virulence is unfortunately very real.
Severe acute COVID-19 illness—indicated by extended time bedridden—is associated with long-term mental morbidity among recovering individuals in the general population. These findings call for increased vigilance of adverse mental health development among patients with a severe acute disease phase of COVID-19.
In summary, in hospitalized patients with COVID the antibody response to infection indicates induction of virus-specific ASCs both through extrafollicular and germinal center responses that predict a more durable immune response in patients recovering from severe disease.
March 11, 2022
Children and adolescents aged 5–15 years were tested for SARS-CoV-2 weekly, irrespective of symptoms, during July 2021–February 2022. Approximately one half of Omicron infections in unvaccinated children and adolescents were asymptomatic. Two doses of Pfizer-BioNTech COVID-19 vaccine reduced the risk of Omicron infection by 31% among children aged 5–11 years and by 59% among persons aged 12–15 years.
March 10, 2022
Wide-ranging genetic study of severe COVID finds common risk factors
Scientists have identified a host of genetic variants that are linked to an increased risk of developing severe COVID-191. These variants affect processes ranging from immune-system signalling to blood clotting, and understanding them could help researchers to target new therapies for people who are critically ill.
March 9, 2022
Efficacy of Antiviral Agents against the SARS-CoV-2 Omicron Subvariant BA.2
The susceptibilities of omicron/BA.2 (NCD1288) to remdesivir, molnupiravir, and nirmatrelvir were similar to those of the ancestral strain and other variants of concern (i.e., 50% inhibitory concentration values for these three agents that differed by factors of 2.5 to 4.5, 0.7 to 1.6, and 1.5 to 3.3, respectively). Clinical studies are warranted to determine whether these antiviral therapies are indeed effective against omicron/BA.2 infections. Our data indicate that some therapeutic monoclonal antibodies (REGN10987–REGN10933, COV2-2196–COV2-2130, and S309) have lower neutralizing activity against omicron/BA.2 than against earlier variant strains.
Effect of mRNA Vaccine Boosters against SARS-CoV-2 Omicron Infection in Qatar
The messenger RNA (mRNA) boosters were highly effective against symptomatic delta infection, but they were less effective against symptomatic omicron infection. However, with both variants, mRNA boosters led to strong protection against Covid-19–related hospitalization and death.
Resistance Mutations in SARS-CoV-2 Delta Variant after Sotrovimab Use
These data show the persistence of viable SARS-CoV-2 in patients after sotrovimab infusions and the rapid development of spike gene mutations associated with high-level sotrovimab resistance in vitro. These findings underscore the importance of stewardship of monoclonal antibodies, particularly because sotrovimab is one of the few monoclonal antibodies with retained activity against the B.1.1.529 (omicron) variant. Postmarketing genomic surveillance of patients who receive monoclonal antibodies for the treatment of SARS-CoV-2 infection is prudent in order to minimize the risk of both treatment failure and the transmission of potentially resistant SARS-CoV-2 variants in health care settings and the community, given that SARS-CoV-2 may be isolated up to 24 days after sotrovimab treatment.
School Masking Policies and Secondary SARS-CoV-2 Transmission
1,112,899 students and 157,069 staff attended 61 K–12 districts across 9 states that met inclusion criteria. The districts reported 40,601 primary and 3,085 secondary infections. Six districts had optional masking policies, 9 had partial masking policies, and 46 had universal masking. Districts that optionally masked throughout the study period had 3.6 times the rate of secondary transmission as universally masked districts. For every 100 community-acquired cases, universally masked districts had 7.3 predicted secondary infections, while optionally masked districts had 26.4.
Despite the success of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, there remains a need for more prevention and treatment options for individuals remaining at risk of coronavirus disease 2019 (COVID-19). Monoclonal antibodies (mAbs) against the viral spike protein have potential to both prevent and treat COVID-19 and reduce the risk of severe disease and death. Here, we describe AZD7442, a combination of two mAbs, AZD8895 (tixagevimab) and AZD1061 (cilgavimab), that simultaneously bind to distinct, nonoverlapping epitopes on the spike protein receptor binding domain to neutralize SARS-CoV-2. Initially isolated from individuals with prior SARS-CoV-2 infection, the two mAbs were designed to extend their half-lives and reduce effector functions. The AZD7442 mAbs individually prevent the spike protein from binding to angiotensin-converting enzyme 2 receptor, blocking virus cell entry, and neutralize all tested SARS-CoV-2 variants of concern. In a nonhuman primate model of SARS-CoV-2 infection, prophylactic AZD7442 administration prevented infection, whereas therapeutic administration accelerated virus clearance from the lung. In an ongoing phase 1 study in healthy participants (NCT04507256), a 300-mg intramuscular injection of AZD7442 provided SARS-CoV-2 serum geometric mean neutralizing titers greater than 10-fold above those of convalescent serum for at least 3 months, which remained threefold above those of convalescent serum at 9 months after AZD7442 administration. About 1 to 2% of serum AZD7442 was detected in nasal mucosa, a site of SARS-CoV-2 infection. Extrapolation of the time course of serum AZD7442 concentration suggests AZD7442 may provide up to 12 months of protection and benefit individuals at high-risk of COVID-19.
March 8, 2022
In Arkansas during August–October 2021, districts with universal mask requirements had a 23% lower incidence of COVID-19 among staff members and students compared with districts without mask requirements. Masks remain an important part of a multicomponent approach to prevent COVID-19 in K–12 settings, especially in communities with high levels of COVID-19.
March 7, 2022
SARS-CoV-2 is associated with changes in brain structure in UK Biobank
We identified significant longitudinal effects when comparing the two groups, including: (i) greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, (ii) greater changes in markers of tissue damage in regions functionally-connected to the primary olfactory cortex, and (iii) greater reduction in global brain size. The infected participants also showed on average larger cognitive decline between the two timepoints. Importantly, these imaging and cognitive longitudinal effects were still seen after excluding the 15 cases who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease via olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious impact can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow up.
Safety data from more than 298 million doses of mRNA COVID-19 vaccine administered in the first 6 months of the US vaccination programme show that most reported adverse events were mild and short in duration.
Secondary Attack Rates for Omicron and Delta Variants of SARS-CoV-2 in Norwegian Households
Secondary attack rate of SARS-CoV-2 in Norwegian households was moderately higher when the index case had the Omicron variant rather than the Delta variant.
March 4, 2022
This cross-sectional study found an association between different SDOH measures and COVID-19 mortality that varied across racial and ethnic groups and community types. Future research is needed that explores the different dimensions and regional patterns of SDOH to address health inequity and guide policies and programs.
COVID-19 vaccination coverage with the first dose of the primary vaccination series was lower in rural (58.5%) than in urban counties (75.4%); disparities have increased more than twofold since April 2021. Receipt of booster or additional doses was similarly low in both rural and urban counties.
March 3, 2022
In this cohort study, COVID-19–dedicated hospitals had multiple benefits, including providing high-volume repetitive treatment and isolating patients with the infection. This experience suggests improved in-hospital mortality for patients treated at dedicated hospitals owing to improved processes of care and supports the use of establishing cohorts for future pandemics.
Assessment of Clinical Effectiveness of BNT162b2 COVID-19 Vaccine in US Adolescents
In this retrospective case-control study of US adolescents, 2 doses of BNT162b2 vaccine appeared to provide excellent protection for at least 4 months after immunization against both symptomatic and asymptomatic SARS-CoV-2 infections.
March 2, 2022
SARS-CoV-2 VOCs appear to be associated with increased relative virulence of infection in all age groups, though low absolute numbers of outcomes in younger individuals make estimates in these groups imprecise.
Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant
Primary immunization with two doses of ChAdOx1 nCoV-19 or BNT162b2 vaccine provided limited protection against symptomatic disease caused by the omicron variant. A BNT162b2 or mRNA-1273 booster after either the ChAdOx1 nCoV-19 or BNT162b2 primary course substantially increased protection, but that protection waned over time.
Effectiveness of Ad26.COV2.S Vaccine vs BNT162b2 Vaccine for COVID-19 Hospitalizations
This study found that the Ad26.COV2.S vaccine is less effective against COVID-19–related hospitalization than the BNT162b2 vaccine. These results strengthen the evidence supporting a second dose in people who received the Ad26.COV2.S vaccine by an mRNA vaccine as recommended in both France and the US.
Association of COVID-19 Infection With Survival After In-Hospital Cardiac Arrest Among US Adults
The absolute survival rate we observed for US patients with IHCA and COVID-19 (11.9%) was higher than the survival rates reported initially (0%,1 2.9%,2 and 3.0%3), which likely represented the isolated experience of health systems overwhelmed early during the pandemic. Our findings are consistent with those of Hayek et al5 (12.0% survival in 400 patients with COVID-19 in 68 ICUs) and Mitchell et al6 (11.9% survival in 260 patients with COVID-19 at 11 hospitals) and extend the previous findings by adding a comparison group of patients without COVID and including non-ICU patients from a larger group of hospitals. We believe that these data will be relevant to health care providers and hospital administrators as the COVID-19 pandemic continues. Because IHCA survival among patients with COVID-19 in this study was not as poor as reported previously, we believe that COVID-19 infection alone should not be used as a criterion for withholding resuscitation care from hospitalized patients.
Drug overdose mortality is increasingly becoming a racial justice issue in the US. Our results suggest that drug overdose mortality has been exacerbated during the COVID-19 pandemic. Providing individuals with a safer supply of drugs, closing gaps in health care access (eg, harm reduction services and medications for opioid use disorder), ending routine incarceration of individuals with substance use disorders, and addressing the social conditions of people who use drugs represent urgently needed, evidence-based strategies that can be used to reduce increasing inequalities in overdose rates.
An analysis of data from nearly 154 000 US veterans with SARS-CoV-2 infection provides a grim preliminary answer to the question: What are COVID-19’s long-term cardiovascular outcomes? The study, published in Nature Medicine by researchers at the Veterans Affairs (VA) St Louis Health Care System, found that in the year after recovering from the illness’s acute phase, patients had increased risks of an array of cardiovascular problems, including abnormal heart rhythms, heart muscle inflammation, blood clots, strokes, myocardial infarction, and heart failure. What’s more, the heightened risks were evident even among those who weren’t hospitalized with acute COVID-19.
March 1, 2022
Among persons aged 12–17 years, reactions after Pfizer-BioNTech booster vaccination were generally mild to moderate and transient; the frequency of local and systemic reactions reported to v-safe after a booster dose were equal to or slightly higher than after the second primary dose. Myocarditis was less frequently reported after a booster dose than a second primary dose.
Two doses protect against COVID-19–associated emergency department and urgent care encounters among children and adolescents. However, vaccine effectiveness (VE) was lower during Omicron predominance and decreased with time since vaccination; a booster dose restored VE to 81% among adolescents aged 16–17 years. Overall, 2-dose VE against COVID-19–associated hospitalization was 73%–94%.
Peripheral Neuropathy Evaluations of Patients With Prolonged Long COVID
Among evaluated patients with long COVID, prolonged, often disabling, small-fiber neuropathy after mild SARS-CoV-2 was most common, beginning within 1 month of COVID-19 onset. Various evidence suggested infection-triggered immune dysregulation as a common mechanism.
March 2022
Cumulatively, we confirmed 1,508 individuals diagnostically, 62% of these through the surveillance program and the remainder through diagnostic tests of symptomatic individuals administered on or off campus. The total strategy, including intensification of testing given case clusters early in the semester, was associated with reduced transmission following rapid case increases upon entry in Fall semester in August 2020, again in early November 2020, and upon re-entry for Spring semester in January 2021. During the Fall semester daily asymptomatic test positivity initially peaked at 4.1% but fell below 0.5% by mid-semester, averaging 0.84% across the Fall semester, with similar levels of control in Spring 2021.
February 28, 2022
At the population-level, where the majority of test-positives (96.0%) were not hospitalized during acute infection, a considerable proportion experience post-acute symptoms and sequelae 6-12 months after infection. Six to twelve months after the test date, the risks of 18 out of 21 physical symptoms were elevated among test-positives and one third (29.6%) of the test-positives experienced at least one physical post-acute symptom.
In this bayesian reanalysis of a previous meta-analysis of 15 randomized clinical trials comprising 5339 hospitalized patients with COVID-19 treated with tocilizumab and corticosteroids, those receiving simple oxygen only or noninvasive ventilation were associated with a clinically meaningful mortality benefit. In contrast, for those receiving invasive mechanical ventilation, an association with benefit was uncertain.
Caregiver COVID-19 Vaccination Status in Pediatric Hospitals—Ethics of Exclusion
Pediatric medicine has long promoted the benefits of vaccination. An approach to caregivers who visit a pediatric hospital and are unvaccinated against COVID-19 must respect that hospital’s mission to promote COVID-19 vaccination as an important means to safeguard children’s health. Such an approach may include strategies to engage with vaccine-hesitant caregivers and facilitate vaccination. Unvaccinated caregivers can be accommodated in a manner that ensures the safety of other inpatient children, caregivers, and health care workers (eg, via symptom screening, masking, and avoidance of common spaces) and that ensures that no child’s care is compromised by the absence of a caregiver at such a vulnerable time. In facilities that provide adult and pediatric care, unvaccinated caregivers of children and adults should be treated differently. Exclusion of a child’s caregiver on the basis of vaccination status is not ethically permissible except under grave circumstances because such an exclusion would violate a child’s right to health care, for which their caregiver is indispensable under most circumstances. Similarly, measures that ignore caregiver vaccination status and fail to promote vaccination fall short of the mission of pediatric institutions to promote vaccination to safeguard children’s health within and beyond the hospital. Thus, in the balance of accountabilities, care of the sick child requires continued inclusion of caregivers, whereas accountability for broader public health requires continued attention to and encouragement of wide-scale COVID-19 vaccination.
Differences in State COVID-19 Vaccine Mandates for Schoolteachers and Childcare Professionals
Less than about half of states requiring COVID-19 vaccination or routine testing of schoolteachers included childcare professionals, suggesting an unwarranted disparity between childcare and school settings in states’ efforts to promote vaccination. Several arguments favor vaccinating childcare professionals. First, both staff and children in childcare programs may be at higher risk for contracting COVID-19 than those in schools, because very young children are currently ineligible for vaccination and possibly less adherent to nonpharmaceutical interventions (eg, masking, social distancing). Second, childcare professionals have lower COVID-19 vaccine uptake compared with schoolteachers (78% vs 90% as of late spring 20213). Third, childcare professionals are disproportionately more racial and ethnic minority individuals, and therefore may be at greater risk for COVID-19–related morbidity and mortality (17.3% and 19.3% are Black and Hispanic individuals vs 12.1% and 13.0% of school personnel, respectively4).
In the Omicron era, the effectiveness against cases of BNT162b2 declined rapidly for children, particularly those 5-11 years. However, vaccination of children 5-11 years was protective against severe disease and is recommended. These results highlight the potential need to study alternative vaccine dosing for children and the continued importance layered protections, including mask wearing, to prevent infection and transmission.
The 64Cu-CR3022-probe also demonstrated dynamic changes occurring between 1- and 2-weeks post-infection. Remarkably, a robust signal was seen in the male genital tract (MGT) of all three animals studied. Infection of the MGT was validated by immunofluorescence imaging of infected cells in the testicular and penile tissue and severe pathology was observed in the testes of one animal at 2-weeks post-infection. The results presented here underscore the utility of using immunoPET to study the dynamics of SARS-CoV-2 infection to understand its pathogenicity and discover new anatomical sites of viral replication. We provide direct evidence for SARS-CoV-2 infection of the MGT in rhesus macaques revealing the possible pathologic outcomes of viral replication at these sites.
February 26, 2022
SARS-CoV-2 emergence very likely resulted from at least two zoonotic events
SARS-CoV-2 genomic diversity early in the COVID-19 pandemic points to emergence via repeated zoonotic event.
The Huanan market was the epicenter of SARS-CoV-2 emergence
GeographicalclusteringoftheearliestknownCOVID-19casesandtheproximityofpositiveenvironmentalsamplestolive-animalvendorssuggestthattheHuananSeafoodWholesaleMarketinWuhanwasthesiteof origin of the COVID-19 pandemic.
February 25, 2022
Between 5 and 9 days after symptom onset or after initial diagnosis with SARS-CoV-2 infection, 54% of persons had positive SARS-CoV-2 antigen test results. The proportion of positive results declined over time. Negative follow-up antigen test results were associated with asymptomatic infection, previous infection, and being vaccinated.
Among 173 vaccinated adults with COVID-19 undergoing serial reverse transcription–polymerase chain reaction (RT-PCR) testing during Omicron predominance, 46% received a negative or high cycle threshold RT-PCR test result on or before day 6 postdiagnosis. Although a positive RT-PCR test result does not necessarily indicate infectiousness, these data indicate that persons with COVID-19 should continue to take precautions, including correct and consistent mask use, for a full 10 days after symptom onset or after initial positive test result if they are asymptomatic.
In a study of household transmission in four U.S. jurisdictions, Omicron infection resulted in high transmission among household contacts, particularly among those who lived with index patients who were not vaccinated or who did not take measures to reduce the risk of transmission to household contacts.
Highly divergent white-tailed deer SARS-CoV-2 with potential deer-to-human transmission
Wildlife reservoirs of SARS-CoV-2 can lead to viral adaptation and spillback from wildlife to humans (Oude Munnink et al., 2021). In North America, there is evidence of spillover of SARS-CoV-2 from humans to white-tailed deer (Odocoileus virginianus), but no evidence of transmission from deer to humans (Hale et al., 2021; Kotwa et al., 2022; Kuchipudi et al., 2021). Through a multidisciplinary research collaboration for SARS-CoV-2 surveillance in Canadian wildlife, we identified a new and highly divergent lineage of SARS-CoV-2. This lineage has 76 consensus mutations including 37 previously associated with non-human animal hosts, 23 of which were not previously reported in deer. There were also mutational signatures of host adaptation under neutral selection. Phylogenetic analysis revealed an epidemiologically linked human case from the same geographic region and sampling period. Together, our findings represent the first evidence of a highly divergent lineage of SARS-CoV-2 in white-tailed deer and of deer-to-human transmission.
Surveillance of SARS-CoV-2 in the environment and animal samples of the Huanan Seafood Market
Herein, we presented the SARS-CoV-2 detection results of 1380 samples collected from the environment and the animals within the market in early 2020. By SARS-CoV-2-specific RT-qPCR, 73 environmental samples tested positive for SARS-CoV-2 and three live viruses were successfully isolated. The viruses from the market shared nucleotide identity of 99.980% to 99.993% with the human isolate HCoV/Wuhan/IVDC-HB-01. In contrast, no virus was detected in the animal swabs covering 18 species of animals in the market. The SARS-COV-2 nucleic acids in the positive environmental samples showed significant correlation of abundance of Homo sapiens with SARS-CoV-2. In summary, this study provided convincing evidence of the prevalence of SARS-CoV-2 in the Huanan Seafood Market during the early stage of COVID-19 outbreak.
February 24, 2022
Our findings show that numbers of children affected by COVID-19-associated orphanhood and caregiver death almost doubled in 6 months compared with the amount after the first 14 months of the pandemic. Over the entire 20-month period, 5·0 million COVID-19 deaths meant that 5·2 million children lost a parent or caregiver. Our data on children's ages and circumstances should support pandemic response planning for children globally.
February 23, 2022
Population Immunity and Covid-19 Severity with Omicron Variant in South Africa
Widespread underlying SARS-CoV-2 seropositivity was observed in Gauteng before the omicron-dominant wave of Covid-19. Epidemiologic data showed a decoupling of hospitalizations and deaths from infections while omicron was circulating.
Addressing Vaccine Inequity — Covid-19 Vaccines as a Global Public Good
The first peer-reviewed clinical trial evidence that a Covid-19 vaccine provided robust protection against SARS-CoV-2 infection was published in the Journal in December 2020, less than a year after the sequence of the viral genome was reported. This unprecedentedly rapid development of vaccines was a scientific triumph. In the year since, about 62% of the world’s population has received at least one dose of a Covid-19 vaccine, and 54% have completed the primary vaccine series. This would appear to be a landmark success in global health mobilization.
February 22, 2022
Using surveillance results from Dec 14, 2020, to Aug 31, 2021, we identified 21 individuals with MIS-C after COVID-19 vaccination. Of these 21 individuals, median age was 16 years (range 12–20); 13 (62%) were male and eight (38%) were female. All 21 were hospitalised: 12 (57%) were admitted to an intensive care unit and all were discharged home. 15 (71%) of 21 individuals had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. As of Aug 31, 2021, 21 335 331 individuals aged 12–20 years had received one or more doses of a COVID-19 vaccine, making the overall reporting rate for MIS-C after vaccination 1·0 case per million individuals receiving one or more doses in this age group. The reporting rate in only those without evidence of SARS-CoV-2 infection was 0·3 cases per million vaccinated individuals.
February 21, 2022
Risk of Second Allergic Reaction to SARS-CoV-2 Vaccines
This study suggests that there is a low risk of a severe immediate allergic reaction associated with a second SARS-CoV-2 mRNA vaccine dose among persons who had an immediate allergic reaction to their first dose.
COVID-19 vaccine efficacy or effectiveness against severe disease remained high, although it did decrease somewhat by 6 months after full vaccination. By contrast, vaccine efficacy or effectiveness against infection and symptomatic disease decreased approximately 20–30 percentage points by 6 months. The decrease in vaccine efficacy or effectiveness is likely caused by, at least in part, waning immunity, although an effect of bias cannot be ruled out. Evaluating vaccine efficacy or effectiveness beyond 6 months will be crucial for updating COVID-19 vaccine policy.
Forty-five long COVID patients, mean age 45 (6-71), 73.3% female, with prolonged symptoms evolving for a mean of 15.2 months (5-22) were tested. Dogs discriminated in a positive way 23/45 (51.1%) long COVID patients versus 0/188 (0%) control healthy individuals (p<.0001). Our data provide arguments for the persistence of viral antigens at least in some long COVID patients and raise the possibility of future therapeutic options.
February 18, 2022
Weekly ED visits among adolescent females (aged 12–17 years) increased for two MHCs (eating and tic disorders) during 2020, four (depression, eating, tic, and obsessive-compulsive disorders) during 2021, and five (anxiety; trauma and stressor-related; eating; tic; and obsessive-compulsive disorders) and overall MHC visits during January 2022, compared with 2019. The proportion of ED visits with eating disorders doubled among adolescent females; those for tic disorders approximately tripled during the pandemic.
Compared with 2019, overall pediatric emergency department visits decreased by 51%, 22%, and 23% during 2020, 2021, and January 2022, respectively. COVID-19 visits predominated across all pediatric ages; visits for other respiratory illnesses mostly declined. Number and proportion of visits increased for certain injuries (e.g., firearm injuries, self-harm, and drug poisonings), some chronic diseases, and behavioral health concerns, with variations by age group.
Attack rates among a cohort of persons attending a convention were high, but lower among infected attendees’ household members. There were fewer infections among vaccinated attendees who had received a COVID-19 vaccine booster dose.
Despite multiple introductions as evidenced by detection of at least three sublineages of SARS-CoV-2, this investigation did not find evidence of widespread transmission among a highly vaccinated population at a large event in an indoor setting where mask use was required and monitored.
On July 27, 2021, a fully vaccinated* crew member on a U.S. Navy ship who had been symptomatic with cough and congestion for 4 days was evaluated in the ship’s onboard medical department and received a positive test result† for SARS-CoV-2, the virus that causes COVID-19. The ship had approximately 350 personnel on board§; COVID-19 vaccination rate was >98%.
Decoupling of omicron variant infections and severe COVID-19
SARS-CoV-2 omicron (B.1.1.529) was designated a variant of concern by WHO because of specific mutations that might increase transmissibility, risk of reinfection, or vaccine breakthrough infection. Many of these mutations affect the receptor-binding domain and N-terminal domain of the spike protein, which might, paradoxically, increase binding to ACE-2 while evading antibody recognition.
In this open-label randomized clinical trial of high-risk patients with COVID-19 in Malaysia, a 5-day course of oral ivermectin administered during the first week of illness did not reduce the risk of developing severe disease compared with standard of care alone. The study findings do not support the use of ivermectin for patients with COVID-19.
Public opinion about the COVID-19 pandemic in the US is deeply divided by political affiliation, including beliefs about the value of ineffective COVID-19 treatments such as hydroxychloroquine sulfate, an antimalarial drug, and ivermectin, an antiparasitic drug. There is increased prescribing of these treatments despite evidence against their effectiveness. We hypothesized that the county-level volume of prescriptions for hydroxychloroquine and ivermectin—but not other, similar medications—would be associated with county-level political voting patterns in the 2020 US presidential election.
SARS-CoV-2 spread and hospitalisations in paediatric patients during the omicron surge
Although several studies have shown that the omicron wave is associated with a lower hospitalisation rate per infection than previous COVID-19 waves, primarily because of milder illness, the number of paediatric patients with omicron in many countries is surpassing the number of paediatric COVID-19 cases seen in those previous waves. The current study, consistent with previous research, shows the possibility that a large increase in the number of COVID-19 cases, even if milder on average, can increase the absolute number of paediatric patients with severe outcomes. These conditions can overwhelm an already strained health-care system, and be further exacerbated during seasonal increases of expected respiratory illness among children.
Between Oct 31 and Dec 11, 2021, 6287 children and adolescents in Tshwane District were recorded as having COVID-19. During this period, 2550 people with COVID-19 were hospitalised, of whom 462 (18%) were aged 19 years or younger. The number of paediatric cases was higher than in the three previous SARS-CoV-2 waves, uncharacteristically increasing ahead of adult hospitalisations. 75 viral samples from adults and children in the district were sequenced, of which 74 (99%) were of the omicron variant. Detailed clinical notes were available for 138 (75%) of 183 children aged ≤13 years with COVID-19 who were hospitalised. 87 (63%) of 138 children were aged 0–4 years. In 61 (44%) of 138 cases COVID-19 was the primary diagnosis, among whom symptoms included fever (37 [61%] of 61), cough (35 [57%]), shortness of breath (19 [31%]), seizures (19 [31%]), vomiting (16 [26%]), and diarrhoea (15 [25%]). Median length of hospital stay was 2 days [IQR 1–3]). 122 (88%) of 138 children with available data needed standard ward care and 27 (20%) needed oxygen therapy. Seven (5%) of 138 children were ventilated and four (3%) died during the study period, all related to complex underlying copathologies. All children and 77 (92%) of 84 parents or guardians with available data were unvaccinated to COVID-19.
February 17, 2022
Mental health in people with covid-19
Altogether, the findings suggest that people with covid-19 are experiencing increased rates of mental health outcomes, which could have far-reaching consequences. The increased risk of opioid use is of particular concern, especially considering the high rates of opioid use disorders pre-pandemic. The increased risks of mental health outcomes in people with covid-19 demands greater attention now to mitigate much more serious downstream consequences in the future.
Challenges in Inferring Intrinsic Severity of the SARS-CoV-2 Omicron Variant
Active genomic surveillance and transparent communication by South African scientists and public health practitioners recently heralded a new, rapidly circulating SARS-CoV-2 variant, now called omicron. Scientists and the public have been closely monitoring the clinical effects of the omicron-variant wave that has rapidly swept through the population in order to estimate the variant’s relative transmissibility, capability for immune evasion, and severity as compared with previous variants.
Endothelial cell-activating antibodies in COVID-19
Serum and plasma from patients with COVID-19 increased surface expression of cell adhesion molecules. Furthermore, levels of soluble ICAM-1 and E-selectin were elevated in patient serum and tracked with disease severity. The presence of circulating antiphospholipid antibodies was a strong marker of the ability of COVID-19 serum to activate endothelium. Depletion of total IgG from antiphospholipid antibody-positive serum markedly restrained upregulation of cell adhesion molecules. Conversely, supplementation of control serum with patient IgG was sufficient to trigger endothelial activation.
February 16, 2022
Bat coronaviruses related to SARS-CoV-2 and infectious for human cells
The animal reservoir of SARS-CoV-2 is unknown despite reports of various SARS-CoV-2-related viruses in Asian Rhinolophus bats1–4, including the closest virus from R. affinis, RaTG135,6 and in pangolins7–9. SARS-CoV-2 presents a mosaic genome, to which different progenitors contribute. The spike sequence determines the binding affinity and accessibility of its receptor-binding domain (RBD) to the cellular angiotensin-converting enzyme 2 (ACE2) receptor and is responsible for host range10–12. SARS-CoV-2 progenitor bat viruses genetically close to SARS-CoV-2 and able to enter human cells through a human ACE2 pathway have not yet been identified, though they would be key in understanding the origin of the epidemics. Here we show that such viruses indeed circulate in cave bats living in the limestone karstic terrain in North Laos, within the Indochinese peninsula. We found that the RBDs of these viruses differ from that of SARS-CoV-2 by only one or two residues at the interface with ACE2, bind more efficiently to the hACE2 protein than the SARS-CoV-2 Wuhan strain isolated in early human cases, and mediate hACE2-dependent entry and replication in human cells, which is inhibited by antibodies neutralizing SARS-CoV-2. None of these bat viruses harbors a furin cleavage site in the spike. Our findings therefore indicate that bat-borne SARS-CoV-2-like viruses potentially infectious for humans circulate in Rhinolophus spp. in the Indochinese peninsula.
Risks of mental health outcomes in people with covid-19: cohort study
The findings suggest that people who survive the acute phase of covid-19 are at increased risk of an array of incident mental health disorders. Tackling mental health disorders among survivors of covid-19 should be a priority.
Protection against SARS-CoV-2 after Covid-19 Vaccination and Previous Infection
Two doses of BNT162b2 vaccine were associated with high short-term protection against SARS-CoV-2 infection; this protection waned considerably after 6 months. Infection-acquired immunity boosted with vaccination remained high more than 1 year after infection.
Effectiveness of the BNT162b2 Vaccine after Recovery from Covid-19
A total of 149,032 patients who had recovered from SARS-CoV-2 infection met the eligibility criteria. Of these patients, 83,356 (56%) received subsequent vaccination during the 270-day study period. Reinfection occurred in 354 of the vaccinated patients (2.46 cases per 100,000 persons per day) and in 2168 of 65,676 unvaccinated patients (10.21 cases per 100,000 persons per day). Vaccine effectiveness was estimated at 82% (95% confidence interval [CI], 80 to 84) among patients who were 16 to 64 years of age and 60% (95% CI, 36 to 76) among those 65 years of age or older. No significant difference in vaccine effectiveness was found for one dose as compared with two doses.
Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19
Treatment of symptomatic Covid-19 with nirmatrelvir plus ritonavir resulted in a risk of progression to severe Covid-19 that was 89% lower than the risk with placebo, without evident safety concerns.
February 15, 2022
Virological characteristics of 1 SARS-CoV-2 BA.2 variant
Soon after the emergence and global spread of a new severe acute respiratory syndrome coronavirus (SARS-CoV-2) Omicron lineage, BA.1, another Omicron lineage, BA.2, has initiated outcompeting BA.1. Statistical analysis shows that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralisation experiments show that the vaccine-induced humoral immunity fails to function against BA.2 like BA.1, and notably, the antigenicity of BA.2 is different from BA.1. Cell culture experiments show that BA.2 is more replicative in human nasal epithelial cells and more fusogenic than BA.1. Furthermore, infection experiments using hamsters show that BA.2 is more pathogenic than BA.1. Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1.
Effectiveness of maternal completion of a 2-dose primary mRNA COVID-19 vaccination series during pregnancy against COVID-19 hospitalization among infants aged <6 months was 61% (95% CI = 31% to 78%). Effectiveness of completion of the primary COVID-19 vaccine series early and later in pregnancy was 32% (95% CI = –43% to 68%) and 80% (95% CI = 55% to 91%), respectively.
Coinciding with increased circulation of the Omicron variant, COVID-19–associated hospitalization rates among children and adolescents aged 0–17 years increased rapidly in late December 2021, especially among children aged 0–4 years who are not yet eligible for vaccination. Throughout the periods of Delta and Omicron predominance, hospitalization rates remained lower among fully vaccinated adolescents aged 12–17 years than among unvaccinated adolescents.
4th Dose COVID mRNA Vaccines’ Immunogenicity & Efficacy Against Omicron VOC
The fourth COVID-19 mRNA dose restores antibody titers to peak post-third dose titers. Low efficacy in preventing mild or asymptomatic Omicron infections and the infectious potential of breakthrough cases raise the urgency of next generation vaccine development.
February 14, 2022
Generation time of the alpha and delta SARS-CoV-2 variants: an epidemiological analysis
Between February and August, 2021, 227 households consisting of 559 participants were recruited to the UKHSA study. The alpha variant was detected or assumed to be responsible for infections in 131 households (243 infections in 334 participants) recruited in February–May, and the delta variant in 96 households (174 infections in 225 participants) in May–August. The mean intrinsic generation time was shorter for the delta variant (4·7 days, 95% credible interval [CI] 4·1–5·6) than the alpha variant (5·5 days, 4·7–6·5), with 92% posterior probability. The mean household generation time was 28% (95% CI 0–48%) shorter for the delta variant (3·2 days, 95% CI 2·5–4·2) than the alpha variant (4·5 days, 3·7–5·4), with 97·5% posterior probability.
February 13, 2022
Extrapolated to the US population we estimated approximately 135,000 excess deaths during the study period in persons >= 18 years old. Our estimates are an underestimate of all excess deaths that have occurred since vaccine became available because our analysis period was limited to May 30 to December 4, 2021 and many excess deaths occurred before and after this period. In summary, we used retrospective data to provide an estimate of the substantial number of COVID-19 deaths among the unvaccinated illustrating the importance of vaccination to prevent further unnecessary mortality during this pandemic.
Among 39 766 employees, 8037 (20%) previously infected and the remaining previously vaccinated, COVID-19 occurred in 6230 (16%) during the study. Risk of COVID-19 increased with time since POIC. In multivariable analysis, boosting was independently associated with lower risk of COVID-19 among those with vaccine-induced immunity (HR, .43; 95% CI, .41-.46) as well as those with natural immunity (HR, .66; 95% CI, .58-.76). Among those with natural immunity, receiving 2 compared to 1 dose of vaccine was associated with higher risk of COVID-19 (HR, 1.54; 95% CI, 1.21-1.97).
February 12, 2022
Tip of the iceberg: erectile dysfunction and COVID-19
The novel severe acute respiratory syndrome coronavirus 2 caused the coronavirus 2019 (COVID-19) pandemic that resulted in more than 150 million infections and 3.5 million deaths globally. COVID-19 affected men more than women, emerging with more severe disease and higher mortality rates. Androgens may be responsible for the underlying reason of more severe disease, as androgen receptors have been implicated to mediate viral cell entry and infection. Besides, male reproductive organs have been reported to be affected by the especially severe disease, resulting in erectile dysfunction (ED). In this narrative review, we aimed to gather possible mechanisms of the development of ED led by COVID-19. Current evidence illuminates endothelial dysfunction, direct testicular damage, and the psychological burden of COVID-19 that are of the pathways of ED. Although the proposed underlying mechanisms partly fail to answer the questions by which COVID-19 leads to ED, it is important to monitor men who recovered from COVID-19 regarding the sexual dysfunction sequelae of infection and address the long‐term consequences.
Offline: Complacency threatens progress against COVID-19
Hans Kluge, WHO's Regional Director for Europe, has been reported as saying that European nations could soon be entering a “long period of tranquillity” as the pandemic abates. Pointing out that mortality from COVID-19 seemed to be plateauing, he suggested the continent was approaching a “plausible endgame” and an “enduring peace”. As WHO's chief spokesperson for the 53 countries that make up his regional responsibility, Kluge was no doubt seeking to strike an optimistic and encouraging note. But it is disappointing that he took such a narrow geographical perspective about a global pandemic. His words promote a false reassurance that could breed complacency, even conceit.
February 11, 2022
Vaccine effectiveness (VE) against COVID-19–associated emergency department/urgent care (ED/UC) visits and hospitalizations was higher after the third dose than after the second dose but waned with time since vaccination. During the Omicron-predominant period, VE against COVID-19–associated ED/UC visits and hospitalizations was 87% and 91%, respectively, during the 2 months after a third dose and decreased to 66% and 78% by the fourth month after a third dose. Protection against hospitalizations exceeded that against ED/UC visits.
Review of surveillance data found that local and systemic reactions were less frequent after a homologous COVID-19 mRNA vaccine booster dose than after the second primary vaccine dose. Myocarditis was rarely reported following an mRNA vaccine booster dose.
The dynamic landscape of SARS-CoV-2 variants in 2021, including Delta- and Omicron-driven resurgences of SARS-CoV-2 transmission across the United States, underscores the importance of robust genomic surveillance efforts to inform public health planning and practice.
February 10, 2022
Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients
Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19.
Molnupiravir — A Step toward Orally Bioavailable Therapies for Covid-19
Vaccines must be the primary mode of protection against SARS-CoV-2; however, orally bioavailable medications will become an essential tool for physicians in the management of this horrible disease. Of note, although the data have not been peer-reviewed, Pfizer has announced the efficacy of its orally bioavailable protease inhibitor, Paxlovid, and Gilead has reported a benefit of ambulatory therapy with remdesivir. Data for both medications demand peer review. The availability of medications with different mechanisms of action offers the opportunity for creating combination therapies that are potentially synergistic and less likely to lead to resistance.
Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico
NVX-CoV2373 was safe and effective for the prevention of Covid-19. Most breakthrough cases were caused by contemporary variant strains.
Of 55 patients in the intention-to-treat group (median age 35 years (IQR: 20); 35 women (64%); 18 African American (33%); 14 Hispanic (26%)), 52 (95%) completed the trial, submitting 1358 electronic symptom surveys. Time to symptom resolution was not statistically improved (p=0.4). Rate of symptom resolution was improved for patients taking famotidine (p<0.0001). Estimated 50% reduction of overall baseline symptom scores were achieved at 8.2 days (95% CI: 7 to 9.8 days) for famotidine and 11.4 days (95% CI: 10.3 to 12.6 days) for placebo treated patients. Differences were independent of patient sex, race or ethnicity. Five self-limiting adverse events occurred (famotidine, n=2 (40%); placebo, n=3 (60%)). On day 7, fewer patients on famotidine had detectable interferon alpha plasma levels (p=0.04). Plasma immunoglobulin type G levels to SARS-CoV-2 nucleocapsid core protein were similar between both arms.
Heart-disease risk soars after COVID — even with a mild case
Even a mild case of COVID-19 can increase a person’s risk of cardiovascular problems for at least a year after diagnosis, a new study shows. Researchers found that rates of many conditions, such as heart failure and stroke, were substantially higher in people who had recovered from COVID-19 than in similar people who hadn’t had the disease.
February 9, 2022
We used an innovative multiple instance learning-based ML approach and droplet segmentation to analyze droplets. Amongst all confounding factors, we discriminated between COVID-positive and COVID-negative individuals yielding receiver operating coefficient curves with an area under curve (AUC) of 0.8 in both males (79% sensitivity and 75% specificity) and females (84% sensitivity and 64% specificity). Taking the sex of the saliva donor into account increased the AUC by 5%.
In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving oropharyngeal clearance of SARS-CoV-2 at 3 days postenrollment was not statistically significantly different between patients given placebo and those given niclosamide. Niclosamide was well-tolerated.
In this cross-sectional study using data for 555 372 student athlete and 3 482 845 nonathlete student SARS-CoV-2 tests reported from 12 National Collegiate Athletic Association Division I institutions, participation in collegiate athletics was not associated with increased test positivity in student athletes compared with nonathlete students.
Protection against the Omicron Variant from Previous SARS-CoV-2 Infection
Overall, in a national database study in Qatar, we found that the effectiveness of previous infection in preventing reinfection with the alpha, beta, and delta variants of SARS-CoV-2 was robust (at approximately 90%), findings that confirmed earlier estimates. Such protection against reinfection with the omicron variant was lower (approximately 60%) but still considerable. In addition, the protection of previous infection against hospitalization or death caused by reinfection appeared to be robust, regardless of variant.
Final Analysis of Efficacy and Safety of Single-Dose Ad26.COV2.S
A single dose of Ad26.COV2.S provided 52.9% protection against moderate to severe–critical Covid-19. Protection varied according to variant; higher protection was observed against severe Covid-19, medical intervention, and death than against other end points and lasted for 6 months or longer.
Effectiveness of Homologous or Heterologous Covid-19 Boosters in Veterans
Overall, documented infections, including moderate and severe or critical disease, were uncommon among veterans who had received either homologous or heterologous boosters. Heterologous mRNA boosting may better protect against incident infection in persons who were initially vaccinated with an adenoviral-vector vaccine.
An anchor in troubled times: Trust in science before and within the COVID-19 pandemic
Researchers, policy makers and science communicators have become increasingly been interested in factors that affect public’s trust in science. Recently, one such potentially important driving factor has emerged, the COVID-19 pandemic. Have trust in science and other science-related beliefs changed in Germany from before to during the pandemic? To investigate this, we re-analyzed data from a set of representative surveys conducted in April, May, and November 2020, which were obtained as part of the German survey Science Barometer, and compared it to data from the last annual Science Barometer survey that took place before the pandemic, (in September 2019). Results indicate that German’s trust in science increased substantially after the pandemic began and slightly declined in the months thereafter, still being higher in November 2020 than in September 2019. Moreover, trust was closely related to expectations about how politics should handle the pandemic. We also find that increases of trust were most pronounced among the higher-educated. But as the pandemic unfolded, decreases of trust were more likely among supporters of the populist right-wing party AfD. We discuss the sustainability of these dynamics as well as implications for science communication.
February 8, 2022
The emerging SARS-CoV-2 variants of concern (VOC) threaten the effectiveness of current COVID-19 vaccines administered intramuscularly and designed to only target the spike protein. There is a pressing need to develop next-generation vaccine strategies for broader and long-lasting protection. Using adenoviral vectors (Ad) of human and chimpanzee origin, we evaluated Ad-vectored trivalent COVID-19 vaccines expressing Spike-1, Nucleocapsid and RdRp antigens in murine models. We show that single-dose intranasal immunization, particularly with chimpanzee Ad-vectored vaccine, is superior to intramuscular immunization in induction of the tripartite protective immunity consisting of local and systemic antibody responses, mucosal tissue-resident memory T cells and mucosal trained innate immunity. We further show that intranasal immunization provides protection against both the ancestral SARS-CoV-2 and two VOC, B.1.1.7 and B.1.351. Our findings indicate that respiratory mucosal delivery of Ad-vectored multivalent vaccine represents an effective next-generation COVID-19 vaccine strategy to induce all-around mucosal immunity against current and future VOC.
Opinion: Wastewater analysis can be a powerful public health tool—if it’s done sensibly
The coronavirus disease 2019 (COVID-19) pandemic sparked an explosion of interest in wastewater-based epidemiology (WBE; also known as wastewater monitoring or wastewater surveillance). Much has been said, in the scientific literature and popular press alike, about the public health value of tracking severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in wastewater. Emergence and spread of the omicron variant has recently pushed WBE for COVID-19 management back into headlines. Unfortunately, coverage of the potential of WBE is rarely balanced by a practical discussion of limitations and tradeoffs, especially when it comes to issues beyond technical challenges encountered in the lab.
Tracking COVID-19 infections: time for change
One of the best ways the world has to get a clear view of COVID-19 is going underused. It’s time to exploit the power of random sampling.
As SARS-CoV-2 transmission continues to evolve, understanding how location-specific variations in non-pharmaceutical interventions and behaviors contributed to disease transmission during the initial epidemic wave will be key for future control strategies. We offer a rigorous statistical analysis of the relative effectiveness of the timing of both official stay-at-home orders and population mobility reductions during the initial stage of the US epidemic. We use a Bayesian hierarchical regression to fit county-level mortality data from the first case on Jan 21 2020 through Apr 20 2020 and quantify associations between the timing of stay-at-home orders and population mobility with epidemic control. We find that among 882 counties with an early local epidemic, a 10-day delay in the enactment of stay-at-home orders would have been associated with 14,700 additional deaths by Apr 20 (95% credible interval, 9,100, 21,500), whereas shifting orders 10 days earlier would have been associated with nearly 15,700 fewer lives lost (95% credible interval, 11,350, 18,950). Analogous estimates are available for reductions in mobility—which typically occurred before stay-at-home orders—and are also stratified by county urbanicity, showing significant heterogeneity. Results underscore the importance of timely policy and behavioral action for early-stage epidemic control.
Long COVID and kids: more research is urgently needed
Long COVID is a term devised by patients to describe the lingering symptoms they experience well after an initial bout of COVID-19. The symptoms vary widely, but some of the most common are fatigue, shortness of breath, cognitive dysfunction (also called brain fog) and post-exertional malaise, in which even minor physical activity leads to lasting exhaustion. Between one-fifth and one-third of those with long COVID remain ill at least 12 weeks after a diagnosis of COVID-19, and a significant number continue to experience symptoms many months later. Many want the condition to be considered a disability.
Severe acute lung injury has few treatment options and a high mortality rate. Upon injury, neutrophils infiltrate the lungs and form neutrophil extracellular traps (NETs), damaging the lungs and driving an exacerbated immune response. Unfortunately, no drug preventing NET formation has completed clinical development. Here, we report that disulfiram —an FDA-approved drug for alcohol use disorder— dramatically reduced NETs, increased survival, improved blood oxygenation, and reduced lung edema in a transfusion-related acute lung injury (TRALI) mouse model. We then tested whether disulfiram could confer protection in the context of SARS-CoV-2 infection, as NETs are elevated in patients with severe COVID-19. In SARS-CoV-2-infected golden hamsters, disulfiram reduced NETs and perivascular fibrosis in the lungs, and downregulated innate immune and complement/coagulation pathways, suggesting that it could be beneficial for COVID-19 patients. In conclusion, an existing FDA-approved drug can block NET formation and improve disease course in two rodent models of lung injury for which treatment options are limited.
Viral RNA may be edited by enzymes of the ADAR family that deaminate adenosine residues with ensuing A→G mutations. We found multiple A→G mutations in minor viral populations of the SARS-CoV-2 genome. A→G mutations accumulated in the receptor binding domain of the spike gene, which may cause structural changes by altering binding to the ACE2 receptor. Presence of A→G mutations in minor viral populations was associated with reduced viral load, implying that ADAR may limit viral replication. Analyses of >250,000 European samples from 2020 revealed that A→G mutations in SARS-CoV-2 RNA were inversely correlated with mortality as a reflection of incidence. ADAR may thus be important in providing new variants of SARS-CoV-2 with altered infectivity and transmissibility.
February 7, 2022
In this retrospective cohort study that included 14 104 patients, a composite outcome of maternal death or serious morbidity related to hypertensive disorders of pregnancy, postpartum hemorrhage, or infection other than SARS-CoV-2 occurred significantly more frequently in individuals with SARS-CoV-2 infection compared with individuals without SARS-CoV-2 infection (13.4% vs 9.2%, respectively).
This study found that the majority of infants born to COVID-vaccinated mothers had persistent anti-S antibodies at 6 months, compared with infants born to mothers with SARS-CoV-2 infection. Understanding the persistence of maternal antibody levels in infants is important because COVID-19 infections in this age group account for a disproportionate burden of pediatric SARS-CoV-2–associated morbidity6 and because COVID-19 vaccines are not currently planned for administration to infants younger than 6 months. Study limitations include the small number of infants, the longer mean time to follow-up in the infected group (due to pragmatic constraints related to timing of COVID-19 surges in Boston and the availability of participants for timely follow-up), and the reporting of antibody titers rather than clinical outcomes. Although the antibody titer known to be protective against COVID-19 in infants is unknown, these findings provide further incentive for pregnant individuals to pursue COVID-19 vaccination.
Long-term cardiovascular outcomes of COVID-19
We show that, beyond the first 30 d after infection, individuals with COVID-19 are at increased risk of incident cardiovascular disease spanning several categories, including cerebrovascular disorders, dysrhythmias, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure and thromboembolic disease. These risks and burdens were evident even among individuals who were not hospitalized during the acute phase of the infection and increased in a graded fashion according to the care setting during the acute phase (non-hospitalized, hospitalized and admitted to intensive care). Our results provide evidence that the risk and 1-year burden of cardiovascular disease in survivors of acute COVID-19 are substantial. Care pathways of those surviving the acute episode of COVID-19 should include attention to cardiovascular health and disease.
We developed the mCARMEN respiratory virus panel (RVP) to test for up to 21 viruses, including SARS-CoV-2, other coronaviruses and both influenza strains, and demonstrated its diagnostic-grade performance on 525 patient specimens in an academic setting and 166 specimens in a clinical setting. We further developed an mCARMEN panel to enable identification of 6 SARS-CoV-2 variant lineages, including Delta and Omicron, and evaluated it on 2,088 patient specimens, with near-perfect concordance to sequencing-based variant classification. Lastly, we implemented a combined Cas13 and Cas12 approach that enables quantitative measurement of SARS-CoV-2 and influenza A viral copies in samples. The mCARMEN platform enables high-throughput surveillance of multiple viruses and variants simultaneously, enabling rapid detection of SARS-CoV-2 variants.
Looking back, the initial spread of COVID-19 in early 2020 illustrates that clinicians, epidemiologists and behavioral scientists around the world greatly underestimated the scope and intensity of resistance to mitigation measures that would follow. Many in the medical community have remained wedded to the view that direct observation of the soaring volume of death and morbidity associated with coronavirus infections will convert most people into adherents of mitigation measures. Hence, most public health communications on mask-wearing, social distancing, and vaccination stubbornly focus on and attempt to leverage efficacy data, patient testimonies, and the clout of clinicians, politicians, athletes and social media influencers, to increase public uptake.
There were 4,248 (39.7%) COVID-19 patients with ACI, with most (93%) developed ACI on or within a day after admission. In-hospital mortality odds ratio of ACI patients was 4.45 [95%CI: 3.92, 5.05, p<0.001] compared to non-ACI patients. Of the 2,880 ACI survivors, 1,114 (38.7%) returned to our hospitals 2.5 months on average post-discharge, of which only 302 (44.9%) out of 673 patients recovered from ACI. There were no significant differences in demographics, race, ethnicity, major commodities, and length of hospital stay between groups. Prediction of ACI recovery post-discharge using the top predictors (troponin, creatinine, lymphocyte, sodium, lactate dehydrogenase, lymphocytes and hematocrit) at discharge yielded 63.73%-75.73% accuracy.
Adolescents who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but had a higher prevalence of single and, particularly, multiple symptoms at the time of PCR testing and 3 months later. Clinicians should consider multiple symptoms that affect functioning and recognise different clusters of symptoms. The multiple and varied symptoms show that a multicomponent intervention will be required, and that mental and physical health symptoms occur concurrently, reflecting their close relationship.
February 5, 2022
WHO concerned over COVID-19 health-care waste
A WHO report published on Feb 1, has found serious shortfalls in COVID-19 health-care waste practices, following an analysis of waste generated through a UN initiative to supply countries with personal protective equipment (PPE) and diagnostic kits for their COVID-19 pandemic response. “Evidence on the amount of health care waste generated, the lack of resourcing to safely manage waste, and the incomplete attention to environmental and climate impacts demonstrates that a more holistic approach is needed” the report concluded.
February 4, 2022
Consistent use of a face mask or respirator in indoor public settings was associated with lower odds of a positive SARS-CoV-2 test result (adjusted odds ratio = 0.44). Use of respirators with higher filtration capacity was associated with the most protection, compared with no mask use.
SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to antibody neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-specific vaccines would enhance immunity and protection.Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing antibody titers against D614G were 4760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (pre-boost), respectively, and 320 and 110 for Omicron. Two weeks after boost, titers against D614G and Omicron increased to 5360 and 2980, respectively, for mRNA-1273 and 2670 and 1930 for mRNA-Omicron. Following either boost, 70-80% of spike-specific B cells were cross-reactive against both WA1 and Omicron.Significant and equivalent control of virus replication in lower airways was observed following either boost. Therefore, an Omicron boost may not provide greater immunity or protection compared to a boost with the current mRNA-1273 vaccine.
In this cohort study of 338 024 persons younger than 20 years and 1 790 886 persons 20 years or older who were tested for SARS-CoV-2, new diagnoses of shortness of breath, nonspecific heart rate abnormalities, and type 2 diabetes were more common among those hospitalized after positive compared with negative test results; fatigue was more common among those aged 20 years or older.
Among adults hospitalized with SARS-CoV-2 infection during Omicron predominance, COVID-19 vaccination, including with a booster dose, was associated with lower likelihood of intensive care unit admission. Compared with patients during the period of Delta predominance, Omicron-period patients had less severe illness, largely driven by an increased proportion who were fully vaccinated. Approximately 20% of early Omicron-period hospitalizations were for non–COVID-19 conditions, particularly among young and vaccinated adults.
During March 1, 2020–October 26, 2021, approximately 2,500,000 COVID-19 cases and 58,000 COVID-19–associated deaths occurred in the state of New York.* New York has the highest U.S. per capita rate of persons living with diagnosed HIV infection (PLWDH), and population-level analyses adjusting for age, sex, and region have shown that PLWDH are more likely to be hospitalized for and to experience an in-hospital death from COVID-19 than are those not known to be PLWDH (1). CDC considers PLWDH who have a low CD4 cell count or who are not receiving HIV treatment to be at elevated risk for severe COVID-19–associated outcomes.
COVID-19 vaccination coverage and vaccine confidence were higher among gay or lesbian adults than among heterosexual adults and higher among gay men than gay or lesbian women. There were no significant differences in vaccination coverage among persons based on gender identity. Vaccination coverage was lowest among non-Hispanic Black LGBT persons across all categories of sexual orientation and gender identity.
The costs and benefits of primary prevention of zoonotic pandemics
Humans have extensive contact with wildlife known to harbor vast numbers of viruses, many of which have not yet spilled into humans. We compute the annualized damages from emerging viral zoonoses. We explore three practical actions to minimize the impact of future pandemics: better surveillance of pathogen spillover and development of global databases of virus genomics and serology, better management of wildlife trade, and substantial reduction of deforestation. We find that these primary pandemic prevention actions cost less than 1/20th the value of lives lost each year to emerging viral zoonoses and have substantial cobenefits.
Anti–SARS-CoV-2 Monoclonal Antibody Distribution to High-risk Medicare Beneficiaries, 2020-2021
Among nonhospitalized Medicare beneficiaries with a COVID-19 diagnosis between November 2020 and August 2021, only 7.2% received mAb therapy. In many cases, patients at the highest risk of severe disease were the least likely to receive mAb therapy. There was also extreme variation geographically.
February 3, 2022
Effectiveness of BNT162b2 Vaccine against Omicron Variant in South Africa
In early November 2021, the B.1.1.529 (omicron) variant was first identified in South Africa and has rapidly become the dominant variant in Gauteng province, where a third wave of coronavirus disease 2019 (Covid-19) driven by the B.1.617.2 (delta) variant had largely subsided. As of November 15, the omicron variant was being detected in more than 75% of Covid-19–positive tests that were sequenced in South Africa.
This case series leveraged more than 190 000 COVID-19 surveillance tests for 14 894 individuals, including 1603 positive test results, at a midsized Midwestern university from January 6 to May 20, 2021. By April 2021, the highly transmissible Alpha (B.1.1.7) variant was the only variant resulting in persistent numbers of positive cases. An increase in vaccination coverage was associated with a decrease in COVID-19 cases in the campus population.
Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness
Of 1176 patients admitted, 253 had records of a 25(OH)D level prior to COVID-19 infection. A lower vitamin D status was more common in patients with the severe or critical disease (<20 ng/mL [87.4%]) than in individuals with mild or moderate disease (<20 ng/mL [34.3%] p < 0.001). Patients with vitamin D deficiency (<20 ng/mL) were 14 times more likely to have severe or critical disease than patients with 25(OH)D ≥40 ng/mL (odds ratio [OR], 14; 95% confidence interval [CI], 4 to 51; p < 0.001).
In this cross-sectional study of unvaccinated US adults, antibodies were detected in 99% of individuals who reported a positive COVID-19 test result, in 55% who believed they had COVID-19 but were never tested, and in 11% who believed they had never had COVID-19 infection. Anti-RBD levels were observed after a positive COVID-19 test result up to 20 months, extending previous 6-month durability data. Although evidence of natural immunity in unvaccinated healthy US adults up to 20 months after confirmed COVID-19 infection is encouraging, it is unclear how these antibody levels correlate with protection against future SARS-CoV-2 infections, particularly with emerging variants. The public health implications and long-term understanding of these findings merit further consideration.
In critically ill hospitalised patients with COVID-19 who were receiving invasive mechanical ventilation or extracorporeal membrane oxygenation, treatment with baricitinib compared with placebo (in combination with standard of care, including corticosteroids) reduced mortality, which is consistent with the mortality reduction observed in less severely ill patients in the hospitalised primary COV-BARRIER study population. However, this was an exploratory trial with a relatively small sample size; therefore, further phase 3 trials are needed to confirm these findings.
The improved outcomes of SARS-CoV-2 infections in the UK, especially compared with France and Germany, have been suggested to be a consequence of use of the ChAdOx1 nCoV-19 (Oxford–AstraZeneca) vaccine. From April, 2021, those older than 40 years in the UK received the ChAdOx1 nCoV-19 vaccine, whereas in the EU, BNT162b2 (Pfizer–BioNTech) was the predominant vaccine used. Supporting this contention, the role of T cells in the response to SARS-CoV-2 infection and vaccination has been highlighted, with an enhanced cellular response reported after ChAdOx1 nCoV-19 compared with BNT162b2 vaccination in people aged 80 years or older, potentially related to an adjuvant effect from the adenovirus vector. In this Correspondence, we report results of a prospective study of vaccination responses in a different group of vulnerable individuals known to have a reduced antibody response to vaccines; namely, patients with rheumatoid arthritis on disease modifying antirheumatic drugs (DMARDs).
February 2, 2022
Extending Rivaroxaban After COVID-19 Hospitalization
Patients who are hospitalized with COVID-19 have elevated rates of postdischarge thrombotic events, but uncertainty exists about whether thromboprophylaxis should continue beyond the hospital stay. In a recent phase 3 trial, continuing thromboprophylaxis after patients hospitalized with COVID-19 were discharged reduced major and fatal thromboembolic events without increasing major bleeding.
Challenges in Inferring Intrinsic Severity of the SARS-CoV-2 Omicron Variant
Viruses don’t inevitably evolve toward being less virulent; evolution simply selects those that excel at multiplying. In the case of Covid-19, in which the vast majority of transmission occurs before disease becomes severe, reduced severity may not be directly selected for at all. Indeed, previous SARS-CoV-2 variants with enhanced transmissibility (e.g., alpha and delta) appear to have greater intrinsic severity than their immediate ancestors or the previously dominant variant. Although the reduced CFR seen in the early weeks of South Africa’s omicron-variant wave is better than the alternative, much of the observed difference relates to increased immunity among the people being infected. More time and careful comparisons controlling for age, preexisting immunity, detection bias, lag time, hospital capacity, and other factors will be required to determine omicron’s intrinsic virulence. Given the remarkable pace at which omicron has spread, its societal effects will probably be substantial, particularly considering an intrinsic severity that is higher than crude comparisons might suggest. Our collective intuition regarding how a population-level CFR or IFR relates to a variant’s intrinsic severity needs to be recalibrated over time as immunity accrues — especially with a variant with the immune-evasion capabilities of omicron.
T-cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all individuals
The SARS-CoV-2 Omicron variant (B.1.1.529) contains mutations that mediate escape from antibody responses, although the extent to which these substitutions in spike and non-spike proteins affect T-cell recognition is unknown. Here we show that T-cell responses in individuals with prior infection, vaccination, both prior infection and vaccination, and boosted vaccination are largely preserved to Omicron spike and non-spike proteins. However, we also identify a subset of individuals (∼21%) with a >50% reduction in T-cell reactivity to the Omicron spike. Evaluation of functional CD4+ and CD8+ memory T cell responses confirmed these findings and reveal that reduced recognition to Omicron spike is primarily observed within the CD8+ T cell compartment potentially due to escape from HLA binding. Booster vaccination enhanced T-cell responses to Omicron spike. In contrast to neutralizing immunity, these findings suggest preservation of T-cell responses to the Omicron variant, although with reduced reactivity in some individuals.
February 1, 2022
As of January 8, 2022, during Omicron predominance, COVID-19 incidence and hospitalization rates in Los Angeles County among unvaccinated persons were 3.6 and 23.0 times, respectively, those of fully vaccinated persons with a booster, and 2.0 and 5.3 times, respectively, those among fully vaccinated persons without a booster. During both Delta and Omicron predominance, incidence and hospitalization rates were highest among unvaccinated persons and lowest among vaccinated persons with a booster.
Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge
To establish a novel SARS-CoV-2 human challenge model, 36 volunteers aged 18-29 years without evidence of previous infection or vaccination were inoculated with 10 TCID50 of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally. Two participants were excluded from per protocol analysis due to seroconversion between screening and inoculation. Eighteen (~53%) became infected, with viral load (VL) rising steeply and peaking at ~5 days post-inoculation. Virus was first detected in the throat but rose to significantly higher levels in the nose, peaking at ~8.87 log10 copies/ml (median, 95% CI [8.41,9.53). Viable virus was recoverable from the nose up to ~10 days post-inoculation, on average. There were no serious adverse events. Mild-to-moderate symptoms were reported by 16 (89%) infected individuals, beginning 2-4 days post-inoculation. Anosmia/dysosmia developed more gradually in 12 (67%) participants. No quantitative correlation was noted between VL and symptoms, with high VLs even in asymptomatic infection, followed by the development of serum spike-specific and neutralising antibodies. However, lateral flow results were strongly associated with viable virus and modelling showed that twice-weekly rapid tests could diagnose infection before 70-80% of viable virus had been generated. Thus, in this first SARS-CoV-2 human challenge study, no serious safety signals were detected and the detailed characteristics of early infection and their public health implications were shown.
‘Decoy’ Protein Works Against Multiple Coronavirus Variants in Early Study
The NIH continues to support the development of some very innovative therapies to control SARS-CoV-2, the coronavirus that causes COVID-19. One innovative idea involves a molecular decoy to thwart the coronavirus.
Weekly epidemiological update on COVID-19 - 1 February 2022
Globally, during the week of 24 to 30 January 2022, the number of new COVID-19 cases remained similar to that reported during the previous week, while the number of new deaths increased by 9%. Across the six WHO regions, over 22 million new cases and over 59 000 new deaths were reported. As of 30 January 2022, over 370 million confirmed cases and over 5.6 million deaths have been reported globally.
Imaging and Clinical Features of COVID-19 Breakthrough Infections: A Multicenter Study
Patients with COVID-19 breakthrough infections had a significantly higher proportion of CT scans without pneumonia compared to unvaccinated patients. Vaccinated patients with breakthrough infections had lower likelihood of requiring supplemental oxygen or ICU admission.
Incident Cancer Detection During the COVID-19 Pandemic
We estimate that there is a large volume of undetected cancer cases related to the pandemic, with incidence rates not yet having returned to prepandemic levels and with some cancers more impacted than others. The population profile of those diagnosed with cancer was not different during the pandemic compared with before. Public health messaging and advisories are required to highlight the importance of early presentation with new symptoms to physicians. Ongoing urgent vaccination of the population to achieve herd immunity will allow safe cancer care. Although this pandemic is ongoing, a cancer recovery plan needs to be initiated. Physicians should encourage continued screening and early biopsy for suspected cancers despite the ongoing pandemic.
This cross-sectional study of 386 711 patients in community clinics in Israel found an increase in incidence rates of various infections among children aged 0 to 3 years and in respiratory infections among all age groups during 3 months after the easing of COVID-19–related social restrictions. These findings suggest that as global COVID-19 vaccination rates increase and social restrictions are lifted, patterns of non–SARS-CoV-2 infection transmission observed late spring in Israel may be seen elsewhere, requiring early preparation.
Protection by 4th dose of BNT162b2 against Omicron in Israel
The rate of confirmed infection was lower in people 12 or more days after their fourth dose than among those who received only three doses and those 3 to 7 days after vaccination by factors of 2.0 (95% confidence interval [CI], 2.0 to 2.1) and 1.9 (95% CI, 1.8 to 2.0), respectively. The rate of severe illness was lower by factors of 4.3 (95% CI, 2.4 to 7.6) and 4.0 (95% CI, 2.2 to 7.5).
February 2022
Sex disparities in COVID-19 outcomes in the United States: Quantifying and contextualizing variation
Results demonstrate considerable variation in the sex disparity in COVID-19 cases and mortalities over time and between states. These data suggest that the sex disparity, when present, is modest, and likely varies in relation to context-sensitive variables, which may include health behaviors, preexisting health status, occupation, race/ethnicity, and other markers of social experience.
Much of the harm wrought in patients with cancer by COVID-19 has not been the direct result of infection, but rather has been inflicted indirectly by delayed diagnoses and suspended or aborted treatments.14 This harm is compounded for patients with cancer who have refused vaccination. Our data, in combination with those from other sources, show that the mRNA COVID-19 vaccine is well tolerated by patients with a history of cancer, including those receiving active treatment. Adverse events occurring shortly after vaccination closely resemble those seen in patients without cancer. As noted, our vaccination program, which targeted a sizable population of patients in fragile health, encountered no obstacles of either an administrative or clinical nature to the timely delivery of the vaccine.
New data provide perspective for appreciating the COVID-19 experience for patients with cancer at greatest risk. Patients with cancer may be more resilient to COVID-19 stressors than has been assumed or suggested. Although not immune to the stresses of COVID-19, data show resilience for otherwise heavily burdened patients with NSCLC—ones unable to “shelter in place” but leaving home regularly to receive treatment. Although recent data from >260,000 cancer survivors show patients with LC experience greater distress and disability and poorer quality of life than those with other common cancers, the latter studies do not necessarily capture the whole story. The present data show that, in the face of multiple health stressors and COVID-19, patients with NSCLC demonstrated resilience.
January 31, 2022
The results of this comparative effectiveness study suggest that a low-cost, easy-to-manufacture elastomeric harness may improve the fit and protection of a standard surgical mask. Infrared imaging and OSHA-approved fit testing were used to improve the harness design and optimize both fit and user comfort. The use of rubber-band harnesses with surgical masks has been reported, but they lack the consistency and comfort that can be achieved with manufactured harnesses.
January 30, 2022
Transmission of SARS-CoV-2 Omicron VOC subvariants BA.1 and BA.2: Evidence from Danish Households
We found BA.2 to be associated with an increased susceptibility of infection for unvaccinated individuals (Odds Ratio (OR) 2.19; 95%-CI 1.58-3.04), fully vaccinated individuals (OR 2.45; 95%-CI 1.77-3.40) and booster-vaccinated individuals (OR 2.99; 95%-CI 2.11-4.24), compared to BA.1. We also found an increased transmissibility from unvaccinated primary cases in BA.2 households when compared to BA.1 households, with an OR of 2.62 (95%-CI 1.96-3.52). The pattern of increased transmissibility in BA.2 households was not observed for fully vaccinated and booster-vaccinated primary cases, where the OR of transmission was below 1 for BA.2 compared to BA.1.
January 28, 2022
In a study of hospitalized adults, compared with receipt of 2 mRNA COVID-19 vaccine doses, receipt of a third dose increased vaccine effectiveness against hospitalization among adults without and with immunocompromising conditions, from 82% to 97% and from 69% to 88%, respectively.
Here, we report neutralizing antibody dynamics in a longitudinal cohort of COVID-19 convalescent and infection-naive individuals vaccinated with mRNA BNT162b2 by quantifying anti-SARS-CoV-2-spike antibodies and determining their avidity and neutralization capacity in serum. Using live-virus neutralization assays, we show that a superior infection-neutralizing capacity against all VoCs, including omicron, developed after either two vaccinations in convalescents or after a third vaccination or breakthrough infection of twice-vaccinated, naive individuals. These three consecutive spike antigen exposures resulted in an increasing neutralization capacity per anti-spike antibody unit and were paralleled by stepwise increases in antibody avidity. We conclude that an infection-plus-vaccination-induced hybrid immunity or a triple immunization can induce high-quality antibodies with superior neutralization capacity against VoCs, including omicron.
Over 50% of individually tested Syrian hamsters in the pet shop (8/16) and warehouse (7/12) were positive for SARS-CoV-2 infection in RT-PCR or serological tests. None of dwarf hamsters (n=77), rabbits (n=246), Guinea pigs (n=66), chinchilla (n=116) and mice (n=2) were confirmed positive in RT-PCR tests. SARS-CoV-2 viral genomes deduced from human and hamster cases in this incident all belong to Delta variant of concern (AY.127) that had not been circulating locally prior. These sequences are highly similar, but distinct. The viral genomes obtained from hamsters are phylogenetically related with some sequence heterogeneity and phylogenetic dating suggest infection in these hamsters occurred around 21 November 2021. Two separate transmission events to humans are documented, one leading to onward household spread.
January 27, 2022
Vaccination with BNT162b2 reduces transmission of SARS-CoV-2 to household contacts in Israel
The individual-level effectiveness of vaccines against COVID-19 is well established. However, few studies have examined vaccine effectiveness against transmission. We used a chain binomial model to estimate the effectiveness of vaccination with BNT162b2 (Pfizer-BioNTech mRNA-based vaccine) against household transmission of SARS-CoV-2 in Israel before and after the Delta variant emerged. Vaccination reduced susceptibility to infection by 89.4% [95% confidence interval (CI): 88.7%, 90.0%], whereas vaccine effectiveness against infectiousness given infection was 23.0% (95% CI: −11.3%, 46.7%) during days 10 to 90 after the second dose before June 1, 2021. Total vaccine effectiveness was 91.8% (95% CI: 88.1%, 94.3%). However, vaccine effectiveness is reduced over time as a result of the combined effect of waning of immunity and the emergence of the Delta variant.
Indirect protection of children from SARS-CoV-2 infection through parental vaccination
Children unvaccinated against SARS-CoV-2 may still benefit through protection from vaccinated contacts. We estimated the protection provided to children through parental vaccination with the BNT162b2 vaccine. We studied households without prior infection, consisting of two parents and unvaccinated children, estimating the effect of parental vaccination on the risk of infection for unvaccinated children. We studied two periods separately– an early period (January 17, 2021 - March 28, 2021, Alpha variant, two doses vs. no vaccination) and a late period (July 11, 2021 - September 30, 2021, Delta variant, booster dose vs. two-vaccine doses). We found that having a single vaccinated parent was associated with a 26.0% and 20.8% decreased risk, and having two vaccinated parents was associated with a 71.7% and 58.1% decreased risk, in the early and late periods, respectively. To conclude, parental vaccination confers substantial protection for unvaccinated children in the household.
COVID-19 vaccine surveillance report - Week 4
Four coronavirus (COVID-19) vaccines have now been approved for use in the UK. Rigorous clinical trials have been undertaken to understand the immune response, safety profile and efficacy of these vaccines as part of the regulatory process. Ongoing monitoring of the vaccines as they are rolled out in the population is important to continually ensure that clinical and public health guidance on the vaccination programme is built upon the best available evidence.
In this commentary, we discuss themes that emerged from the symposium about what modern epidemiology as a science may learn from the coronavirus disease 19 (COVID-19) pandemic. We reflect on the successes and limitations of this discipline from multiple perspectives, including junior and senior epidemiologists and scientists on the front lines of generating evidence for the COVID-19 pandemic response from Wuhan, China to Ontario, Canada. These themes include: the role of the traditional scientific process in a public health emergency; epidemiologic methods and data that are critical for an effective pandemic response; the interventions that epidemiologists recommended and interventions that we may explore in the future; inequitable impacts of the COVID-19 pandemic contrasted with homogeneity in epidemiologists’ workforce; effective and honest communication of uncertainty; trust and collaboration; and the extent to which these themes are currently reflected in our training programs and discipline. We look forward to insights from field epidemiologists directly involved in the ongoing response to the COVID-19 pandemic and further reflection from epidemiologists throughout our discipline.
January 26, 2022
Long COVID symptoms of any severity were reported by 9.5% of double-vaccinated study participants, compared with 14.6% of socio-demographically similar participants who were unvaccinated when infected; the corresponding estimates for long COVID symptoms severe enough to result in limitation to day-to-day activities were 5.5% and 8.7% respectively.
Efficacy of Antibodies and Antiviral Drugs against Covid-19 Omicron Variant
In November 2021, the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in South Africa. Since then, omicron has rapidly spread around the world. On November 26, 2021, the World Health Organization designated omicron as a variant of concern. The omicron variant was found to have at least 33 mutations (29 amino acid substitutions, 1 insertion of three amino acids, and 3 small deletions) in its spike (S) protein, as compared with early SARS-CoV-2 strains identified in Wuhan, China.
SARS-CoV-2 Omicron Variant Neutralization after mRNA-1273 Booster Vaccination
The highly transmissible omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of mounting concern globally. The omicron variant carries a large number of spike mutations, including at least 15 mutations in the receptor-binding domain, which is a major target of neutralizing antibodies.
Effects of a Prolonged Booster Interval on Neutralization of Omicron Variant
The coronavirus disease 2019 (Covid-19) pandemic is still ongoing, and the B.1.1.529 (or omicron) variant, first detected in November 2021, has already spread globally. The ability of the omicron variant to escape vaccine-elicited immunity is of great concern. Inactivated vaccines, such as CoronaVac and BBIBP-CorV, and protein subunit vaccines, such as ZF2001, have been widely used in China and several other countries.
Homologous and Heterologous Covid-19 Booster Vaccinations
Of the 458 participants who were enrolled in the trial, 154 received mRNA-1273, 150 received Ad26.COV2.S, and 153 received BNT162b2 as booster vaccines; 1 participant did not receive the assigned vaccine. Reactogenicity was similar to that reported for the primary series. More than half the recipients reported having injection-site pain, malaise, headache, or myalgia. For all combinations, antibody neutralizing titers against a SARS-CoV-2 D614G pseudovirus increased by a factor of 4 to 73, and binding titers increased by a factor of 5 to 55. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20, whereas heterologous boosters increased titers by a factor of 6 to 73. Spike-specific T-cell responses increased in all but the homologous Ad26.COV2.S-boosted subgroup. CD8+ T-cell levels were more durable in the Ad26.COV2.S-primed recipients, and heterologous boosting with the Ad26.COV2.S vaccine substantially increased spike-specific CD8+ T cells in the mRNA vaccine recipients.
Waning mRNA-1273 Vaccine Effectiveness against SARS-CoV-2 Infection in Qatar
We used a test-negative, case–control study design to estimate vaccine effectiveness, applying the same methods used recently to assess waning effectiveness of the BNT162b2 (Pfizer–BioNTech) vaccine in the same population. Case participants (persons with a positive polymerase-chain-reaction [PCR] test for SARS-CoV-2) and controls (PCR-negative persons) were matched one to one according to sex, 10-year age group, nationality, reason for PCR testing, and calendar week of PCR test. Effectiveness was estimated against documented infection (a PCR-positive swab, regardless of the presence of symptoms) and against any severe Covid-19 cases (acute-care hospitalizations), critical Covid-19 cases (intensive care unit hospitalizations), or fatal Covid-19 cases (Covid-19–related deaths).
Effects of a Prolonged Booster Interval on Neutralization of Omicron Variant
These findings support the use of multiple vaccine boosts and prolonged intervals between vaccine doses to protect against highly mutated variants such as omicron in persons who had previously received two priming doses of vaccine or who had previously recovered from SARS-CoV-2. Our results are in accordance with those of previous studies involving messenger RNA vaccine recipients.5Next-generation vaccines that stimulate broad protection against SARS-CoV-2 variants are also needed.
Efficacy of Antibodies and Antiviral Drugs against Covid-19 Omicron Variant
The omicron variant has mutations in both the RNA-dependent RNA polymerase (RdRp) and the main protease of SARS-CoV-2, which are targets for antiviral drugs such as RdRp inhibitors (remdesivir and molnupiravir) and the main protease inhibitor PF-07304814, which arouses concern regarding the decreased effectiveness of these drugs against omicron. Thus, we tested three different antiviral compounds (i.e., remdesivir, molnupiravir, and PF-07304814) for their efficacy against omicron. The in vitro 50% inhibitory concentration (IC50) values of each compound were determined against NC928, NC002, HP127, HP01542, TY7-503, and UW5250. The susceptibilities of omicron to the three compounds were similar to those of the early strain (i.e., IC50 values for remdesivir, molnupiravir, and PF-07304814 that differed by factors of 1.2, 0.8, and 0.7, respectively) (Table 1). These results suggest that all three of these compounds may show efficacy for treating patients infected with the omicron variant.
January 25, 2022
Although disease severity appears lower with the Omicron variant, the high volume of hospitalizations can strain local health care systems and the average daily number of deaths remains substantial. This underscores the importance of national emergency preparedness, specifically, hospital surge capacity and the ability to adequately staff local health care systems. In addition, being up to date on vaccinations and following other recommended prevention strategies are critical to preventing infections, severe illness, or death from COVID-19.
Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement
The SARS-CoV-2 Omicron variant of concern evades antibody-mediated immunity that comes from vaccination or infection with earlier variants due to accumulation of numerous spike mutations. To understand the Omicron antigenic shift, we determined cryo-electron microscopy and X-ray crystal structures of the spike protein and the receptor-binding domain bound to the broadly neutralizing sarbecovirus monoclonal antibody (mAb) S309 (the parent mAb of sotrovimab) and to the human ACE2 receptor. We provide a blueprint for understanding the marked reduction of binding of other therapeutic mAbs that leads to dampened neutralizing activity. Remodeling of interactions between the Omicron receptor-binding domain and human ACE2 likely explains the enhanced affinity for the host receptor relative to the ancestral virus.
Long-COVID symptoms less likely in vaccinated people, Israeli data say
Researchers in Israel report that people who have had both SARS-CoV-2 infection and doses of Pfizer–BioNTech vaccine were much less likely to report any of a range of common long-COVID symptoms than were people who were unvaccinated when infected. In fact, vaccinated people were no more likely to report symptoms than people who’d never caught SARS-CoV-2. The study has not yet been peer reviewed.
Our results show that Omicron had higher positivity rates than Delta among those who received two doses within five months (Omicron = 4.7% vs. Delta = 2.6%), two doses more than five months ago (4.2% vs. 2.9%), and three vaccine doses (2.2% vs. 0.9%). Our estimates of Omicron positivity rates in persons receiving one or two vaccine doses were not significantly lower than unvaccinated persons but were 49.7% lower after three doses. In comparison, the reduction in Delta positivity rates from unvaccinated to 2 vaccine doses was 45.6-49.6% and to 3 vaccine doses was 83.2%. Despite the higher positivity rates for Omicron in vaccinated persons, we still found that 91.2% of the Omicron infections in our study occurred in persons who were eligible for 1 or more vaccine doses at the time of PCR testing. In conclusion, escape from vaccine-induced immunity likely contributed to the rapid rise in Omicron infections.
We find that human immune sera following breakthrough infection and vaccination following natural infection, broadly neutralize SARS-CoV-2 variants to a similar degree. While age negatively correlates with antibody response after vaccination alone, no correlation with age was found in breakthrough or hybrid immune groups. Together, our data suggest that the additional antigen exposure from natural infection substantially boosts the quantity, quality, and breadth of humoral immune response regardless of whether it occurs before or after vaccination.
In this meta-analysis of 8 randomized clinical trials enrolling 2341 participants, individual patient data were monitored in real time and analyzed using a robust bayesian framework and advanced statistical modeling. No association of convalescent plasma with clinical outcomes was found.
Acute ischaemic stroke associated with SARS-CoV-2 infection in North America
There may be a relationship between COVID-19 associated AIS and severe disability or death. We identified several factors that predict worse outcomes, and these outcomes were more frequent compared with global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-dimer, predicted both morbidity and mortality.
Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae
Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.
January 24, 2022
COVID-19: endemic doesn’t mean harmless
The best way to prevent more, more-dangerous or more-transmissible variants from emerging is to stop unconstrained spread, and that requires many integrated public-health interventions, including, crucially, vaccine equity. The more a virus replicates, the greater the chance that problematic variants will arise, most probably where spread is highest. The Alpha variant was first identified in the United Kingdom, Delta was first found in India and Omicron in southern Africa — all places where spread was rampant. Thinking that endemicity is both mild and inevitable is more than wrong, it is dangerous: it sets humanity up for many more years of disease, including unpredictable waves of outbreaks. It is more productive to consider how bad things could get if we keep giving the virus opportunities to outwit us. Then we might do more to ensure that this does not happen.
During the SARS-CoV-2 pandemic, novel and traditional vaccine strategies have been deployed globally. We investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including 3rd dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S and Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines. We analyzed human lymph nodes after infection or mRNA vaccination for correlates of serological differences. Antibody breadth against viral variants is less after infection compared to all vaccines evaluated, but improves over several months. Viral variant infection elicits variant-specific antibodies, but prior mRNA vaccination imprints serological responses toward Wuhan-Hu-1 rather than variant antigens. In contrast to disrupted germinal centers (GCs) in lymph nodes during infection, mRNA vaccination stimulates robust GCs containing vaccine mRNA and spike antigen up to 8 weeks post-vaccination in some cases. SARS-CoV-2 antibody specificity, breadth and maturation are affected by imprinting from exposure history, and distinct histological and antigenic contexts in infection compared to vaccination.
ARCoV was safe and well tolerated at all five doses. The acceptable safety profile, together with the induction of strong humoral and cellular immune responses, support further clinical testing of ARCoV at a large scale.
In September, 2021, at the start of the autumn school term in England, infections were increasing exponentially in children aged 5–17 years, at a time when vaccination rates were low in this age group. In adults, compared to those who received their second dose less than 3 months ago, the higher prevalence of swab positivity at 3–6 months following two doses of the COVID-19 vaccine suggests an increased risk of breakthrough infections during this period. The vaccination programme needs to reach children as well as unvaccinated and partially vaccinated adults to reduce SARS-CoV-2 transmission and associated disruptions to work and education.
The estimated transmission bottleneck size of the Delta variant was generally narrow, with 1-3 virions in 29 donor-recipient transmission pairs. However, the transmission of minor iSNVs resulted in at least 3 of the 34 substitutions that were identified in the outbreak, highlighting the contribution of intra-host variants to population-level viral diversity during rapid spread.
Here, we show that it is possible to generate ultra-potent (IC50 < 2 ng/ml) human neutralizing antibodies directly from a unique semisynthetic naïve antibody library format with affinities, developability properties and neutralization activities comparable to the best from hyperimmune sources. This demonstrates that appropriately designed and constructed naïve antibody libraries can effectively compete with immunization to directly provide therapeutic antibodies against a viral pathogen, without the need for immune sources or downstream optimization.
Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae
We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.
In this exploratory multicenter prospective cohort study that included 246 patients who were alive 1 year following ICU treatment for COVID-19, 74.3% reported physical symptoms, 26.2% reported mental symptoms, and 16.2% reported cognitive symptoms.
January 22, 2022
Neutralization of Omicron SARS-CoV-2 by 2 or 3 doses of BNT162b2 vaccine
We report the antibody neutralization against Omicron SARS-CoV-2 after 2 and 3 doses of BNT162b2 mRNA vaccine. Vaccinated individuals were serially tested for their neutralization against wild-type SARS-CoV-2 (strain USA-WA1/2020) and an engineered USA-WA1/2020 bearing the Omicron spike glycoprotein. Plaque reduction neutralization results showed that at 2 or 4 weeks post-dose-2, the neutralization geometric mean titers (GMTs) were 511 and 20 against the wild-type and Omicron-spike viruses, respectively, suggesting that two doses of BNT162b2 were not sufficient to elicit robust neutralization against Omicron; at 1 month post-dose-3, the neutralization GMTs increased to 1342 and 336, respectively, indicating that three doses of vaccine increased the magnitude and breadth of neutralization against Omicron; at 4 months post-dose-3, the neutralization GMTs decreased to 820 and 171, respectively, suggesting similar neutralization decay kinetics for both variants. The data support a three-dose vaccine strategy and provide the first glimpse of the neutralization durability against Omicron.
January 21, 2022
In 25 U.S. jurisdictions, decreases in case incidence rate ratios for unvaccinated versus fully vaccinated persons with and without booster vaccine doses were observed when the Omicron variant emerged in December 2021. Protection against infection and death during the Delta-predominant period against infection during Omicron emergence were higher among booster vaccine dose recipients, and especially among persons aged 50–64 and ≥65 years.
VE was significantly higher among patients who received their second mRNA COVID-19 vaccine dose <180 days before medical encounters compared with those vaccinated ≥180 days earlier. During both Delta- and Omicron-predominant periods, receipt of a third vaccine dose was highly effective at preventing COVID-19–associated emergency department and urgent care encounters (94% and 82%, respectively) and preventing COVID-19–associated hospitalizations (94% and 90%, respectively).
In this test-negative case-control analysis that included 70 155 tests from symptomatic adults, the likelihood of vaccination with 3 mRNA vaccine doses (vs unvaccinated) was significantly lower among both Omicron (odds ratio, 0.33) and Delta (odds ratio, 0.065) cases than SARS-CoV-2–negative controls; a similar pattern was observed with 3 vaccine doses vs 2 doses (Omicron odds ratio, 0.34; Delta odds ratio, 0.16). These findings suggest that vaccination with 3 doses of mRNA COVID-19 vaccine, compared with being unvaccinated and with receipt of 2 doses, was associated with protection against both the Omicron and Delta variants, although higher odds ratios for the association with Omicron infection suggest less protection for Omicron than for Delta.
Pfizer-BioNTech or Moderna mRNA COVID-19 vaccines are preferred over the Janssen COVID-19 vaccine for primary and booster vaccination. The Janssen COVID-19 vaccine may be considered in some situations, including for persons with a contraindication to receipt of mRNA COVID-19 vaccines.
Changes in COVID-19 Vaccine Hesitancy Among Black and White Individuals in the US
This survey study of 1200 US adults found that COVID-19 vaccine hesitancy decreased more rapidly among Black individuals than among White individuals since December 2020. A key factor associated with this pattern seems to be the fact that Black individuals more rapidly came to believe that vaccines were necessary to protect themselves and their communities.
Booster Vaccination to Prevent COVID-19 in the Era of Omicron
As the US enters the third year of the global coronavirus pandemic, vaccination remains the most effective tool against infections and symptomatic illness. Layered on other public health mitigation tools such as testing and masks, vaccination is central to a larger strategy of control and management of COVID-19 as the pandemic shifts toward endemicity.1 However, emergence of new variants of concern, vaccine hesitancy, and barriers to global vaccine equity have created challenges to containing the pandemic.
The Health Care Workforce Under Stress—Clinician Heal Thyself
The nature and extent of the novel COVID-19 pandemic has been unprecedented, touching all aspects of society. An emerging body of literature has highlighted the substantial mental health toll affecting broad swaths of the general population during the pandemic.
Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron
Omicron replication is markedly attenuated in both the upper and lower respiratory tract of infected K18-hACE2 mice in comparison to that of WT and Delta variant, which results in its dramatically ameliorated lung pathology. When compared with SARS-CoV-2 WT, Alpha, Beta, and Delta variant, infection by the Omicron variant causes the least body weight loss and mortality rate. Overall, our study demonstrates that the Omicron variant is attenuated in virus replication and pathogenicity in mice in comparison with WT and previous variants.
SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters
Despite modeling data suggesting that B.1.1.529 spike can bind more avidly to murine ACE23,4, we observed less infection in 129, C57BL/6, BALB/c, and K18-hACE2 transgenic mice as compared with previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. In wild-type and hACE2 transgenic hamsters, lung infection, clinical disease, and pathology with B.1.1.529 also were milder compared to historical isolates or other SARS-CoV-2 variants of concern. Overall, experiments from the SAVE/NIAID network with several B.1.1.529 isolates demonstrate attenuated lung disease in rodents, which parallels preliminary human clinical data.
These results demonstrate COH04S1-mediated vaccine protection in animal models through different vaccination routes and dose regimens, complementing ongoing investigation of this multiantigen SARS-CoV-2 vaccine in clinical trials.
A guide to immunotherapy for COVID-19
Immune dysregulation is an important component of the pathophysiology of COVID-19. A large body of literature has reported the effect of immune-based therapies in patients with COVID-19, with some remarkable successes such as the use of steroids or anti-cytokine therapies. However, challenges in clinical decision-making arise from the complexity of the disease phenotypes and patient heterogeneity, as well as the variable quality of evidence from immunotherapy studies. This Review aims to support clinical decision-making by providing an overview of the evidence generated by major clinical trials of host-directed therapy. We discuss patient stratification and propose an algorithm to guide the use of immunotherapy strategies in the clinic. This will not only help guide treatment decisions, but may also help to design future trials that investigate immunotherapy in other severe infections.
January 20, 2022
SARS-CoV-2 breakthrough infections elicit potent, broad, and durable neutralizing antibody responses
Although infections among vaccinated individuals lead to milder COVID-19 symptoms relative to those in unvaccinated subjects, the specificity and durability of antibody responses elicited by breakthrough cases remain unknown. Here, we demonstrate that breakthrough infections induce serum-binding and -neutralizing antibody responses that are markedly more potent, durable, and resilient to spike mutations observed in variants than those in subjects who received only 2 doses of vaccine. However, we show that breakthrough cases, subjects who were vaccinated after infection, and individuals vaccinated three times have serum-neutralizing activity of comparable magnitude and breadth, indicating that an increased number of exposures to SARS-CoV-2 antigen(s) enhance the quality of antibody responses. Neutralization of SARS-CoV was moderate, however, underscoring the importance of developing vaccines eliciting broad sarbecovirus immunity for pandemic preparedness.
A prospective cohort study of COVID-19 vaccination, SARS-CoV-2 infection, and fertility
These findings indicate that male SARS-CoV-2 infection may be associated with a short-term decline in fertility and that COVID-19 vaccination does not impair fertility in either partner.
January 19, 2022
Immunogenicity and Reactogenicity of Vaccine Boosters after Ad26.COV2.S Priming
The Ad26.COV2.S and mRNA boosters had an acceptable safety profile and were immunogenic in health care workers who had received a priming dose of Ad26.COV2.S vaccine. The strongest responses occurred after boosting with mRNA-based vaccines. Boosting with any available vaccine was better than not boosting.
Although the epidemiology of COVID-19 might change as new variants emerge, vaccination remains the safest strategy for averting future SARS-CoV-2 infections, hospitalizations, long-term sequelae, and death. Primary vaccination, additional doses, and booster doses are recommended for all eligible persons. Additional future recommendations for vaccine doses might be warranted as the virus and immunity levels change.
No infectious SARS-CoV-2 in breast milk from a cohort of 110 lactating women
SARS-CoV-2 RNA can be found infrequently in the breastmilk after recent infection, but we found no evidence that breastmilk contains an infectious virus or that breastfeeding represents a risk factor for transmission of infection to infants.
From structure to sequence: Antibody discovery using cryoEM
One of the rate-limiting steps in analyzing immune responses to vaccines or infections is the isolation and characterization of monoclonal antibodies. Here, we present a hybrid structural and bioinformatic approach to directly assign the heavy and light chains, identify complementarity-determining regions, and discover sequences from cryoEM density maps of serum-derived polyclonal antibodies bound to an antigen. When combined with next-generation sequencing of immune repertoires, we were able to specifically identify clonal family members, synthesize the monoclonal antibodies, and confirm that they interact with the antigen in a manner equivalent to the corresponding polyclonal antibodies. This structure-based approach for identification of monoclonal antibodies from polyclonal sera opens new avenues for analysis of immune responses and iterative vaccine design.
Today’s MMWR study finds that during the Delta wave, both COVID-19 vaccination and surviving a prior infection provided protection against infection and hospitalization from COVID-19. Scientists reviewed data from New York and California to determine the level of protection offered by COVID-19 vaccines, previous infection, and both. Between May and November 2021, people who were unvaccinated and did not have a prior COVID-19 infection remained at the highest risk of infection and hospitalization, while those who were previously infected, both with or without prior vaccination, had the greatest protection.
Risk factors and abnormal cerebrospinal fluid associate with cognitive symptoms after mild COVID-19
Cognitive post-acute sequelae of SARS-CoV-2 (PASC) can occur after mild COVID-19. Detailed clinical characterizations may inform pathogenesis. We evaluated 22 adults reporting cognitive PASC and 10 not reporting cognitive symptoms after mild SARS-CoV-2 infection through structured interviews, neuropsychological testing, and optional cerebrospinal fluid (CSF) evaluations (53%). Delayed onset of cognitive PASC occurred in 43% and associated with younger age. Cognitive PASC participants had a higher number of pre-existing cognitive risk factors (2.5 vs. 0; p = 0.03) and higher proportion with abnormal CSF findings (77% vs. 0%; p = 0.01) versus controls. Cognitive risk factors and immunologic mechanisms may contribute to cognitive PASC pathogenesis.
The cGAS-STING pathway drives type I IFN immunopathology in COVID-19
Profiling COVID-19 skin manifestations, we uncover a STING-dependent type I IFN signature primarily mediated by macrophages adjacent to areas of endothelial cell damage. Moreover, cGAS-STING activity was detected in lung samples of COVID-19 patients with prominent tissue destruction and associated with type I IFN responses. A lung-on-chip model revealed that, in addition to macrophages, SARS-CoV-2 infection activates cGAS-STING signalling in endothelial cells through mitochondrial DNA release, leading to cell death and type I IFN production. In mice, pharmacological inhibition of STING reduces severe lung inflammation induced by SARS-CoV-2 and improves disease outcome. Collectively, our study establishes a mechanistic basis of pathological type I IFN responses in COVID-19 and reveals a novel principle for the development of host-directed therapeutics.
COVID-19 vaccine makers chase variant-ready vaccines
Pfizer aims to have an Omicron-specific COVID-19 vaccine ready by March. Assuming it gains approval, it will mark the first revision of its mRNA vaccine Comirnaty since the initial Emergency Use Authorization of the vaccine by the US Food and Drug Administration (FDA) on 11 December 2020. The variant-specific booster will also test the responsiveness of the FDA and other major regulators in turning around applications for vaccine revisions.
January 18, 2022
Breakthrough infections with SARS-CoV-2 omicron despite mRNA vaccine booster dose
In-vitro data suggest lower titres of neutralising antibodies against omicron compared to other SARS-CoV-2 lineages following BNT162b2 vaccination but increased titres after a third dose,10, 11, 12 supporting calls for booster doses while the omicron variant appears to be spreading globally. Our study, however, demonstrates insufficient prevention of symptomatic infection in otherwise healthy individuals who had received three doses of COVID-19 mRNA vaccines.
The performance of current antigen tests in paediatric populations under real-life conditions varies broadly. Relevant data were only identified for very few antigen tests on the market, and the risk of bias was mostly unclear due to poor reporting. Additionally, the most common uses of these tests in children (eg, self-testing in schools or parents testing their toddlers before kindergarten) have not been addressed in clinical performance studies yet. The observed low diagnostic sensitivity may impact the planned purpose of the broad implementation of testing programmes.
January 17, 2022
Vaccination with at least two doses of COVID-19 vaccine was associated with a substantial decrease in reporting the most common post-acute COVID-19 symptoms, bringing it back to baseline. Our results suggest that, in addition to reducing the risk of acute illness, COVID-19 vaccination may have a protective effect against long COVID.
Israeli study shows 4th shot of COVID-19 vaccine less effective on Omicron
A fourth shot of COVID-19 vaccine boosts antibodies to even higher levels than the third jab but it is not enough to prevent Omicron infections, according to a preliminary study in Israel.
Israel's Sheba Medical Center has given second booster shots in a trial among its staff and is studying the effect of the Pfizer booster in 154 people after two weeks and the Moderna booster in 120 people after one week, said Gili Regev-Yochay, director of the Infectious Diseases Unit.
The UGT2A1/UGT2A2 locus is associated with COVID-19-related loss of smell or taste
Using online surveys, we collected data regarding COVID-19-related loss of smell or taste from 69,841 individuals. We performed a multi-ancestry genome-wide association study and identified a genome-wide significant locus in the vicinity of the UGT2A1 and UGT2A2 genes. Both genes are expressed in the olfactory epithelium and play a role in metabolizing odorants. These findings provide a genetic link to the biological mechanisms underlying COVID-19-related loss of smell or taste.
SARS-CoV-2 RNA can be detected in exhaled aerosol, sampled during a limited number of breathing and coughing procedures. Detection in aerosol seemed independent of viral load in the upper airway swab as well as of the exhaled number of particles. The infectious potential of the amount of virus detected in aerosol needs to be further explored.
January 14, 2022
Equitable receipt of COVID-19 treatments by race and ethnicity along with vaccines and other prevention practices are essential to reduce inequities in severe COVID-19–associated illness and death.
Standards Required for the Development of CDC Evidence-Based Guidelines
CDC is the nation’s premier health promotion, prevention, and preparedness agency. As such, CDC is an important source of public health and clinical guidelines. If CDC guidelines are to be trusted by partners and the public, they must be clear, valid, and reliable. Methods and processes used in CDC guideline development should follow universally accepted standards. This report describes the standards required by CDC for the development of evidence-based guidelines. These standards cover topics such as guideline scoping, soliciting external input, summarizing evidence, and crafting recommendations. Following these standards can help minimize bias and enhance the quality and consistency of CDC guidelines.
January 13, 2022
Covid-19: Peak of viral shedding is later with omicron variant, Japanese data suggest
Patients with the omicron variant of covid-19 shed virus for longer after symptoms emerge, show data from Japan, potentially jeopardising hopes that the period of isolation for people testing positive could be shortened.
SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland
Vaccine coverage was substantially lower in pregnant women than in the general female population of 18−44 years; 32.3% of women giving birth in October 2021 had two doses of vaccine compared to 77.4% in all women. The extended perinatal mortality rate for women who gave birth within 28 d of a COVID-19 diagnosis was 22.6 per 1,000 births (95% CI 12.9−38.5; pandemic background rate 5.6 per 1,000 births; 452 out of 80,456; 95% CI 5.1−6.2). Overall, 77.4% (3,833 out of 4,950; 95% CI 76.2−78.6) of SARS-CoV-2 infections, 90.9% (748 out of 823; 95% CI 88.7−92.7) of SARS-CoV-2 associated with hospital admission and 98% (102 out of 104; 95% CI 92.5−99.7) of SARS-CoV-2 associated with critical care admission, as well as all baby deaths, occurred in pregnant women who were unvaccinated at the time of COVID-19 diagnosis. Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic.
Comparative Effectiveness of BNT162b2 and mRNA-1273 Vaccines in U.S. Veterans
The 24-week risk of Covid-19 outcomes was low after vaccination with mRNA-1273 or BNT162b2, although risks were lower with mRNA-1273 than with BNT162b2. This pattern was consistent across periods marked by alpha- and delta-variant predominance.
January 12, 2022
Duration of Protection against Mild and Severe Disease by Covid-19 Vaccines
We observed limited waning in vaccine effectiveness against Covid-19–related hospitalization and death at 20 weeks or more after vaccination with two doses of the ChAdOx1-S or BNT162b2 vaccine. Waning was greater in older adults and in those in a clinical risk group.
Effectiveness of BNT162b2 Vaccine against Critical Covid-19 in Adolescents
Among hospitalized adolescent patients, two doses of the BNT162b2 vaccine were highly effective against Covid-19–related hospitalization and ICU admission or the receipt of life support.
Effectiveness of Covid-19 Vaccines over a 9-Month Period in North Carolina
All three Covid-19 vaccines had durable effectiveness in reducing the risks of hospitalization and death. Waning protection against infection over time was due to both declining immunity and the emergence of the delta variant.
SARS-CoV-2 Omicron Variant Neutralization in Serum from Vaccinated and Convalescent Persons
During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, several new viral variants have emerged, leading to the virus becoming more contagious. However, efficient immune escape has not been observed, and vaccines have remained effective. Most recently, the B.1.1.529 (omicron) variant has been described, which the World Health Organization classified as a variant of concern on November 26, 2021.
There is an urgent need to understand how SARS-CoV-2 infects the airway epithelium and in a subset of individuals leads to severe illness or death. Induced pluripotent stem cells (iPSCs) provide a near limitless supply of human cells that can be differentiated into cell types of interest, including airway epithelium, for disease modeling. We present a human iPSC-derived airway epithelial platform, composed of the major airway epithelial cell types, that is permissive to SARS-CoV-2 infection. Subsets of iPSC-airway cells express the SARS-CoV-2 entry factors ACE2 and TMPRSS2. Multiciliated cells are the primary initial target of SARS-CoV-2 infection. Upon infection with SARS-CoV-2, iPSC-airway cells generate robust interferon and inflammatory responses and treatment with remdesivir or camostat methylate causes a decrease in viral propagation and entry, respectively. In conclusion, iPSC-derived airway cells provide a physiologically relevant in vitro model system to interrogate the pathogenesis of, and develop treatment strategies for, COVID-19 pneumonia.
January 11, 2022
Rates of ICU admission and mortality after an outpatient positive test were 0.26 (0.10-0.73) and 0.09 (0.01-0.75) fold as high among cases with Omicron variant infection as compared to cases with Delta variant infection. Zero cases with Omicron variant infection received mechanical ventilation, as compared to 11 cases with Delta variant infections throughout the period of follow-up (two-sided p<0.001). Median duration of hospital stay was 3.4 (2.8-4.1) days shorter for hospitalized cases with Omicron variant infections as compared to hospitalized patients with Delta variant infections, reflecting a 69.6% (64.0-74.5%) reduction in hospital length of stay. Conclusions: During a period with mixed Delta and Omicron variant circulation, SARS-CoV-2 infections with presumed Omicron variant infection were associated with substantially reduced risk of severe clinical endpoints and shorter durations of hospital stay.
Plasma SARS-CoV-2 viral RNA (vRNA) levels are predictive of COVID-19 outcomes in hospitalized patients, but whether plasma vRNA reflects lower respiratory tract (LRT) vRNA levels is unclear. We compared plasma and LRT vRNA levels in simultaneously collected longitudinal samples from mechanically-ventilated patients with COVID-19. LRT and plasma vRNA levels were strongly correlated at first sampling (r=0.83, p<10-8) and then declined in parallel except in non-survivors who exhibited delayed vRNA clearance in LRT samples. Plasma vRNA measurement may offer a practical surrogate of LRT vRNA burden in critically ill patients, especially early in severe disease.
SARS-CoV-2 Reverse Zoonoses to Pumas and Lions, South Africa
One Health genomic surveillance identified transmission of a Delta variant from a zookeeper to the three lions, similar to those circulating in humans in South Africa. One lion developed pneumonia while the other cases had mild infection. Both the puma and lions remained positive for SARS-CoV-2 RNA for up to 7 weeks.
January 10, 2022
Humans experiencing long-COVID with cognitive symptoms (48 subjects) similarly demonstrate elevated CCL11 levels compared to those with long-COVID who lack cognitive symptoms (15 subjects). Impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss in subcortical white matter were evident at 1 week, and persisted until at least 7 weeks, following mild respiratory SARS-CoV-2 infection in mice. Taken together, the findings presented here illustrate striking similarities between neuropathophysiology after cancer therapy and after SARS-CoV-2 infection, and elucidate cellular deficits that may contribute to lasting neurological symptoms following even mild SARS-CoV-2 infection.
The Dynamics of SARS-CoV-2 Infectivity with Changes in Aerosol Microenvironment
The aerosol microenvironment is highly dynamic exposing pathogens, such as the SARS-CoV-2 virus when exhaled in respiratory aerosol, to extreme conditions of solute concentration, pH and evaporative cooling. Yet surviving this environment is a key step in the transmission of such pathogens. Understanding the impact that airborne transport has on pathogens and the influence of environmental conditions on pathogen survival can inform the implementation of strategies to mitigate the spread of diseases such as COVID-19. We report changes in the infectivity of the airborne virus over timescales spanning from 5 s to 20 minutes and demonstrate the role of two microphysical processes in this infectivity loss: particle crystallisation and aerosol droplet pH change.
Our results are thus consistent with pre-existing non-spike cross-reactive memory T cells protecting SARS-CoV-2-naïve contacts from infection, thereby supporting the inclusion of non-spike antigens in second-generation vaccines.
In this cohort study of 1928 health care workers in Israel who were previously vaccinated with a 2-dose series of BNT162b2, administration of a booster dose compared with not receiving one was significantly associated with lower risk of SARS-CoV-2 infection during a median of 39 days of follow-up (adjusted hazard ratio, 0.07).
January 7, 2022
Among 1,228,664 persons who completed primary vaccination during December 2020–October 2021, severe COVID-19–associated outcomes (0.015%) or death (0.0033%) were rare. Risk factors for severe outcomes included age ≥65 years, immunosuppressed, and six other underlying conditions. All persons with severe outcomes had at least one risk factor; 78% of persons who died had at least four.
Rapid Diagnostic Testing for SARS-CoV-2
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author’s clinical recommendations.
Receipt of 2 doses of Pfizer-BioNTech vaccine is highly effective in preventing MIS-C in persons aged 12–18 years. These findings further reinforce the COVID-19 vaccination recommendation for eligible children.
The increased diabetes risk among persons aged <18 years following COVID-19 highlights the importance of COVID-19 prevention strategies in this age group, including vaccination for all eligible persons and chronic disease prevention and treatment.
Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa
Here, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.
False-Positive Results in Rapid Antigen Tests for SARS-CoV-2
The overall rate of false-positive results among the total rapid antigen test screens for SARS-CoV-2 was very low, consistent with other, smaller studies. The cluster of false-positive results from 1 batch was likely the result of manufacturing issues rather than implementation. These results inform the discussion of whether rapid antigen tests will result in too many false-positives that could overwhelm PCR testing capacity in other settings. Also, the results demonstrate the importance of having a comprehensive data system to quickly identify potential issues. With the ability to identify batch issues within 24 hours, workers could return to work, problematic test batches could be discarded, and the public health authorities and manufacturer could be informed. Aside from issues with the batch, false-positives are possible due to the timing of the test (ie, too early or too late in the infectious stage) or quality issues in how the self-test was completed.
In this cohort study including 163 patients, a third vaccine dose strengthened the immune response in 75% of the patients treated with chemotherapy or targeted therapy presenting a weak humoral response after the second dose. The data of this study appear to support the use of a third vaccine dose as a booster dose among patients with active cancer treatment for solid tumors.
Antigenic properties of the SARS-CoV-2 nucleoprotein are altered by the RNA admixture
Therefore, we have established the NP purification method, which completely eliminates the RNA in the NP preparation. Two stages of RNA removal were used: treatment of the crude lysate of E. coli with RNase A and subsequent selective RNA elution with 2 M NaCl solution. The resulting NP without RNA has a significantly better signal-to-noise ratio when used as an ELISA antigen and tested with a control panel of serum samples with antibodies to SARS-CoV-2; therefore, it is preferable for in vitro diagnostic use. The same increase of the signal-to-noise ratio was detected for the free N-terminal domain of the NP. Complete removal of RNA complexed with NP during purification will significantly improve its antigenic properties, and the absence of RNA in NP preparations should be controlled during the production of this antigen.
January 6, 2022
A mighty antibody is the bane of multiple coronaviruses
A newly isolated antibody that blocks SARS-CoV-2 from infecting cells could one day be used to treat infections caused by current and future variants of the virus that causes COVID-19, and even infections from related viruses.
A National Strategy for COVID-19 Medical Countermeasures
The US needs a strategy for a “new normal” of living that includes COVID-19. This “new normal” will occur when total respiratory viral infections, hospitalizations, and deaths inclusive of those from COVID-19 are no higher than what typically occurred in the most severe influenza years before the current pandemic. Integral to achieving and sustaining this “new normal” are both faster development and more efficient deployment of vaccines and therapeutics. While COVID-19 has ushered in new vaccine platforms, repurposed existing therapies, and stimulated rapid development of monoclonal antibody and oral antiviral treatments in record time, much remains to be done to ensure these life-saving medicines are accessible to all.
It is widely believed that self-reported loss of taste can be an indirect consequence of retronasal olfactory dysfunction6; indeed, our study found that even when specifically asked about basic tastes, more than half of patients self-reporting an altered taste perception exhibited a normal gustatory function, while most of them had an olfactory impairment. However, 42% were found to have true hypogeusia. Following evaluation of the scores in relation to age, still 29% exhibited hypogeusia, which has largely been overlooked to date. While olfactory training may help the former group, additional strategies may be needed for those with gustatory impairment.
January 5, 2022
Effect of Covid-19 Vaccination on Transmission of Alpha and Delta Variants
Vaccination was associated with a smaller reduction in transmission of the delta variant than of the alpha variant, and the effects of vaccination decreased over time. PCR Ct values at diagnosis of the index patient only partially explained decreased transmission.
January 4, 2022
These data support the safety of COVID-19 vaccination during pregnancy. CDC recommends COVID-19 vaccination for women who are pregnant, recently pregnant, who are trying to become pregnant now, or who might become pregnant in the future.
In this cohort study of 255 infants born between March and December 2020, exposure to maternal SARS-CoV-2 infection was not associated with differences on any Ages & Stages Questionnaire, 3rd Edition, subdomain at age 6 months, regardless of infection timing or severity. However, both exposed and unexposed infants born during that period had significantly lower scores on gross motor, fine motor, and personal-social subdomains compared with a historical cohort of infants born before the onset of the COVID-19 pandemic.
Understanding the Effects of the Pandemic on Infant Development—The Preterm Problem
As the COVID-19 pandemic grinds toward the end of another year, it makes sense to wonder about the effect on children conceived and born in its shadow. Some of the consequences can be seen in the increasing rates of COVID-19 among infants and young children, particularly among those with comorbid medical conditions. But we must also consider less obvious sequelae: are infants born during the pandemic at greater risk for behavioral or neurodevelopmental problems, either due to exposure to maternal SARS-CoV-2 infection or to the more global effects of trauma and stress? Pregnant women and their infants are vulnerable to the effects of disasters, and evidence suggests that disaster affects maternal mental health and some perinatal health outcomes, particularly among highly exposed women. Prenatal exposure to some viral infections, such as rubella and HIV, increases the risk of neurobehavioral problems in children, and some have hypothesized that SARS-CoV-2 infection could have a similar outcome via in utero exposure to maternal fever, hypoxia, or inflammation.
COVID-19 Deaths Helped Drive Largest Drop in US Life Expectancy in More than 75 Years
Mortality rates for US residents 15 years or older increased sharply in 2020, fueled by nearly 351 000 deaths attributed to COVID-19 during the year. As a result, average US life expectancy at birth declined by nearly 2 years from that in 2019, according to a data brief from the Centers for Disease Control and Prevention’s National Center for Health Statistics (NCHS).
Healthcare workers (HCWs) in the United Kingdom (UK) have been prioritised in the SARS-CoV-2 vaccination agenda, including the ongoing booster programme. We previously reported that 23% of 11,584 HCWs who completed the baseline UK-REACH (UK Research study into Ethnicity And Covid-19 outcomes in Healthcare workers) cohort study questionnaire were hesitant about receiving a SARS-CoV-2 vaccine between 4th December 2020 and 28th February 2021. Vaccine hesitancy was more likely amongst certain ethnic minority groups and was associated with lower trust in employing healthcare organisations and in vaccines themselves. HCWs who were hesitant also reported concerns about vaccine safety and side effects, especially given the speed of vaccine development and roll-out, and expressed a desire to delay vaccination until more people had been vaccinated.
January 3, 2022
Psychological Predictors of Self-reported COVID-19 Outcomes: Results From a Prospective Cohort Study
COVID-19 infection and symptoms may be more common among those experiencing elevated psychological distress. Further research to elucidate the mechanisms underlying these associations is needed.
January 1, 2022
As coronavirus disease 2019 (COVID-19) vaccination is undoubtedly a key to controlling the transmission of COVID-19, owing to its effectiveness, increasing the willingness to receive COVID-19 vaccines is a crucial mission for both vaccine coverage and subsequent global infection control. In this context, COVID-19 vaccine hesitancy, the reluctance to receive COVID-19 vaccines, has become a significant growing public health concern. Although COVID-19 vaccine hesitancy varies across cultural and geographical contexts, general mistrust for vaccines and fear of future adverse events are major concerns among the hesitant. Such mistrust, fear, and the unwillingness to vaccinate, based on misinformation or disinformation, are often cultivated by mass and social media. Since individuals generally use multiple media channels, identifying specific media use, including combinations of media use among the hesitant, is essential to prevent the development of COVID-19 vaccine hesitancy.
Caution required with use of ritonavir-boosted PF-07321332 in COVID-19 management
We read with interest the news that the UK Government has announced deals to procure the oral antivirals for SARS-CoV-2, molnupiravir (Lagevrio, Merck [Branchburg, NJ, USA]) and ritonavir in combination with PF-07321332 (Paxlovid, Pfizer [New York, NY, USA]). Although we welcome further partnership between the government and pharmaceutical industry in the provision of effective agents to manage the COVID-19 pandemic, we urge caution with the widescale use of ritonavir, given its propensity for causing clinically significant drug–drug interactions with commonly prescribed and over-the-counter medications.
December 31, 2021
COVID-19 Vaccine Safety in Children Aged 5–11 Years — United States, November 3–December 19, 2021
Parents and guardians of children aged 5–11 years should be advised that local and systemic reactions are expected after vaccination with Pfizer-BioNTech COVID-19 vaccine and are more common after the second dose.
In real-world conditions among adolescents aged 12–17 years, the Pfizer-BioNTech vaccine was highly effective in preventing SARS-CoV-2 infection.
COVID-19 vaccination and other prevention strategies are important to protect children from COVID-19, particularly children with obesity and other underlying health conditions.
Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron
Here, we investigated the neutralizing and binding activity of sera from convalescent, mRNA double vaccinated, mRNA boosted, convalescent double vaccinated, and convalescent boosted individuals against wild type, B.1.351 and B.1.1.529 SARS-CoV-2 isolates. Neutralizing activity of sera from convalescent and double vaccinated participants was undetectable to very low against B.1.1.529 while neutralizing activity of sera from individuals who had been exposed to spike three or four times was maintained, albeit at significantly reduced levels. Binding to the B.1.1.529 receptor binding domain (RBD) and N-terminal domain (NTD) was reduced in convalescent not vaccinated individuals, but was mostly retained in vaccinated individuals.
December 30, 2021
Plasma Neutralization of the SARS-CoV-2 Omicron Variant
The newly emerged B.1.1.159 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a large number of changes — 32 — in its spike protein relative to that of the original virus (Wuhan-hu-1), particularly in the receptor-binding domain and the N-terminal domain, the primary targets of neutralizing antibodies. Previously, we showed that approximately 20 changes introduced into a synthetic polymutant spike protein (PMS20) are sufficient for substantial evasion of the polyclonal neutralizing antibodies elicited in the majority of persons who have recovered from coronavirus disease 2019 (Covid-19) or have received two doses of an mRNA vaccine. Of note, several changes in the PMS20 spike protein are the same as or similar to changes in the omicron variant.
Paradoxical sex-specific patterns of autoantibody response to SARS-CoV-2 infection
Our results reveal that prior SARS-CoV-2 infection, even in the absence of severe clinical disease, can lead to a broad AAB response that exhibits sex-specific patterns of prevalence and antigen selectivity. Further understanding of the nature of triggered AAB activation among men and women exposed to SARS-CoV-2 will be essential for developing effective interventions against immune-mediated sequelae of COVID-19.
December 29, 2021
Effectiveness of BNT162b2 Vaccine against Omicron Variant in South Africa
Thus, during the proxy omicron period, we saw a maintenance of effectiveness of the BNT162b2 vaccine (albeit at a reduced level) against hospital admission for Covid-19 that was presumed to have been caused by the omicron variant as compared with the rate associated with the delta variant earlier in the year. The addition of a booster dose of vaccine may mitigate this reduction in vaccine effectiveness.
Third BNT162b2 Vaccination Neutralization of SARS-CoV-2 Omicron Infection
Nevertheless, we found low neutralization efficiency with two doses of the BNT162b2 vaccine against the wild-type virus and the delta variant, assessed more than 5 months after receipt of the second dose, and no neutralization efficiency against the omicron variant. The importance of a third vaccine dose is clear, owing to the higher neutralization efficiency (by a factor of 100) against the omicron variant after the third dose than after the second dose; however, even with three vaccine doses, neutralization against the omicron variant was lower (by a factor of 4) than that against the delta variant. The durability of the effect of the third dose of vaccine against Covid-19 is yet to be determined.
Fourteen amino acid substitutions, including N501Y and E484K, and 9 deletions are located in the spike protein. This genotype pattern led to create a new Pangolin lineage named B.1.640.2, which is a phylogenetic sister group to the old B.1.640 lineage renamed B.1.640.1. Both lineages differ by 25 nucleotide substitutions and 33 deletions. The mutation set and phylogenetic position of the genomes obtained here indicate based on our previous definition a new variant we named “IHU”. These data are another example of the unpredictability of the emergence of SARS-CoV-2 variants, and of their introduction in a given geographical area from abroad.
December 28, 2021
Investigation of a SARS-CoV-2 B.1.1.529 (Omicron) Variant Cluster — Nebraska, November–December 2021
The B.1.1.529 (Omicron) variant of SARS-CoV-2 (the virus that causes COVID-19) was first detected in specimens collected on November 11, 2021, in Botswana and on November 14 in South Africa; the first confirmed case of Omicron in the United States was identified in California on December 1, 2021 (1). On November 29, the Nebraska Department of Health and Human Services was notified of six probable cases of COVID-19 in one household, including one case in a man aged 48 years (the index patient) who had recently returned from Nigeria.
December 23, 2021
Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19.
Considerable escape of SARS-CoV-2 Omicron to antibody neutralization
Omicron was totally or partially resistant to neutralization by all mAbs tested. Sera from Pfizer or AstraZeneca vaccine recipients, sampled 5 months after complete vaccination, barely inhibited Omicron. Sera from COVID-19 convalescent patients collected 6 or 12 months post symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titers 6 to 23 fold lower against Omicron than against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and to a large extent vaccine-elicited antibodies. Omicron remains however neutralized by antibodies generated by a booster vaccine dose.
Evolution of enhanced innate immune evasion by SARS-CoV-2
Here we used unbiased abundance proteomics, phosphoproteomics, RNAseq and viral replication assays to show that isolates of the Alpha (B.1.1.7) variant more effectively suppress innate immune responses in airway epithelial cells, compared to first wave isolates. We found that Alpha has dramatically increased subgenomic RNA and protein levels of N, Orf9b and Orf6, all known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein required for RNA sensing adaptor MAVS activation. Moreover, the activity of Orf9b and its association with TOM70 was regulated by phosphorylation. We propose that more effective innate immune suppression, through enhanced expression of specific viral antagonist proteins, increases the likelihood of successful Alpha transmission, and may increase in vivo replication and duration of infection. The importance of mutations outside Spike in adaptation of SARS-CoV-2 to humans is underscored by the observation that similar mutations exist in the Delta and Omicron N/Orf9b regulatory regions.
Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2
By evaluating a panel of monoclonal antibodies to all known epitope clusters on the spike protein, we noted that the activity of 17 of the 19 antibodies tested were either abolished or impaired, including ones currently authorized or approved for use in patients. In addition, we also identified four new spike mutations (S371L, N440K, G446S, and Q493R) that confer greater antibody resistance to B.1.1.529. The Omicron variant presents a serious threat to many existing COVID-19 vaccines and therapies, compelling the development of new interventions that anticipate the evolutionary trajectory of SARS-CoV-2.
Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies
In total, over 85% of the tested NAbs are escaped by Omicron. Regarding NAb drugs, the neutralization potency of LY-CoV016/LY-CoV555, REGN10933/REGN10987, AZD1061/AZD8895, and BRII-196 were greatly reduced by Omicron, while VIR-7831 and DXP-604 still function at reduced efficacy. Together, data suggest Omicron would cause significant humoral immune evasion, while NAbs targeting the sarbecovirus conserved region remain most effective. Our results offer instructions for developing NAb drugs and vaccines against Omicron and future variants.
Evolution of enhanced innate immune evasion by SARS-CoV-2
Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein required for RNA sensing adaptor MAVS activation. Moreover, the activity of Orf9b and its association with TOM70 was regulated by phosphorylation. We propose that more effective innate immune suppression, through enhanced expression of specific viral antagonist proteins, increases the likelihood of successful Alpha transmission, and may increase in vivo replication and duration of infection4. The importance of mutations outside Spike in adaptation of SARS-CoV-2 to humans is underscored by the observation that similar mutations exist in the Delta and Omicron N/Orf9b regulatory regions.
SARS-CoV-2 infection in free-ranging white-tailed deer
The B.1.2 viruses, dominant in humans in Ohio at the time, infected deer in four locations. Probable deer-to-deer transmission of B.1.2, B.1.582, and B.1.596 viruses was observed, allowing the virus to acquire amino acid substitutions in the spike protein (including the receptor-binding domain) and ORF1 that are infrequently seen in humans. No spillback to humans was observed, but these findings demonstrate that SARS-CoV-2 viruses have the capacity to transmit in US wildlife, potentially opening new pathways for evolution. There is an urgent need to establish comprehensive “One Health” programs to monitor deer, the environment, and other wildlife hosts globally.
Considerable escape of SARS-CoV-2 Omicron to antibody neutralization
Omicron was totally or partially resistant to neutralization by all mAbs tested. Sera from Pfizer or AstraZeneca vaccine recipients, sampled 5 months after complete vaccination, barely inhibited Omicron. Sera from COVID-19 convalescent patients collected 6 or 12 months post symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titers 6 to 23 fold lower against Omicron than against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and to a large extent vaccine-elicited antibodies. Omicron remains however neutralized by antibodies generated by a booster vaccine dose.
Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization
Neutralization of ancestral virus was much higher in infected and vaccinated versus vaccinated only participants but both groups showed a 22-fold escape from vaccine elicited neutralization by the Omicron variant. However, in the previously infected and vaccinated group, the level of residual neutralization of Omicron was similar to the level of neutralization of ancestral virus observed in the vaccination only group. These data support the notion that, provided high neutralization capacity is elicited by vaccination/boosting approaches, reasonable effectiveness against Omicron may be maintained.
BNT162b2 Vaccine Booster and Mortality Due to Covid-19
A total of 843,208 participants met the eligibility criteria, of whom 758,118 (90%) received the booster during the 54-day study period. Death due to Covid-19 occurred in 65 participants in the booster group (0.16 per 100,000 persons per day) and in 137 participants in the nonbooster group (2.98 per 100,000 persons per day). The adjusted hazard ratio for death due to Covid-19 in the booster group, as compared with the nonbooster group, was 0.10 (95% confidence interval, 0.07 to 0.14; P<0.001).
Protection against Covid-19 by BNT162b2 Booster across Age Groups
Across the age groups studied, rates of confirmed Covid-19 and severe illness were substantially lower among participants who received a booster dose of the BNT162b2 vaccine than among those who did not.
mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant
Recent surveillance has revealed the emergence of the SARS-CoV-2 Omicron variant (BA.1/B.1.1.529) harboring up to 36 mutations in spike protein, the target of neutralizing antibodies. Given its potential to escape vaccine-induced humoral immunity, we measured the neutralization potency of sera from 88 mRNA-1273, 111 BNT162b, and 40 Ad26.COV2.S vaccine recipients against wild-type, Delta, and Omicron SARS-CoV-2 pseudoviruses. We included individuals that received their primary series recently (<3 months), distantly (6–12 months), or an additional “booster” dose, while accounting for prior SARS-CoV-2 infection. Remarkably, neutralization of Omicron was undetectable in most vaccinees. However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron, only 4–6-fold lower than wild type, suggesting enhanced cross-reactivity of neutralizing antibody responses. In addition, we find that Omicron pseudovirus infects more efficiently than other variants tested. Overall, this study highlights the importance of additional mRNA doses to broaden neutralizing antibody responses against highly divergent SARS-CoV-2 variants.
December 22, 2021
In our cohort of PLWHIV with well-controlled ART, stable viral suppression and robust CD4+ T cell count, inoculation with mRNA-1273 vaccine given 4 weeks apart produced detectable humoral immune response, similar to individuals without HIV infection, supporting vaccination in PLWHIV.
Memory B cells (MBCs) represent a second layer of immune protection against SARS-CoV-2. Whether MBCs elicited by mRNA vaccines can recognize the Omicron variant is of major concern. We used bio-layer interferometry to assess the affinity against the receptor-binding-domain (RBD) of Omicron spike of 313 naturally expressed monoclonal IgG that were previously tested for affinity and neutralization against VOC prior to Omicron. We report here that Omicron evades recognition from a larger fraction of these antibodies than any of the previous VOCs. Additionally, whereas 30% of these antibodies retained high affinity against Omicron-RBD, our analysis suggest that Omicron specifically evades antibodies displaying potent neutralizing activity against the D614G and Beta variant viruses. Further studies are warranted to understand the consequences of a lower memory B cell potency on the overall protection associated with current vaccines.
Our study provides evidence of protection against infection with the Omicron variant after completion of a primary vaccination series with the BNT162b2 or mRNA-1273 vaccines; in particular, we found a VE against the Omicron variant of 55.2% (95% confidence interval (CI): 23.5 to 73.7%) and 36.7% (95% CI: 69.9 to 76.4%) for the BNT162b2 and mRNA-1273 vaccines, respectively, in the first month after primary vaccination. However, the VE is significantly lower than that against Delta infection and declines rapidly over just a few months. The VE is re-established upon revaccination with the BNT162b2 vaccine (54.6%, 95% CI: 30.4 to 70.4%).
Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients
Among nonhospitalized patients who were at high risk for Covid-19 progression, a 3-day course of remdesivir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo
December 21, 2021
Early administration of high titer SARS-CoV-2 convalescent plasma reduced outpatient hospitalizations by more than 50%. High titer convalescent plasma is an effective early outpatient COVID-19 treatment with the advantages of low cost, wide availability, and rapid resilience to variant emergence from viral genetic drift in the face of a changing pandemic.
A domain with three sitting female passengers was defined. Dynamics of droplets released from the mouth of the different passengers during the vocalization of vowel /ɑ/ were investigated in detail. For the conditions evaluated, the droplets were initially driven by the exhaled jet and buoyancy and mainly occupied the back region of a hypothetical front row. This effect was more noticeable when droplets were released from positions closer to the ventilation system such as window and middle seat positions. The droplets from the passenger located farthest from the ventilation inlet, such as the one in the aisle, were more affected by the flow from the beginning of the exhalation, and many of the droplets were initially moved to the bottom of the domain. The droplets then encountered primary and secondary flows, which were responsible for the longitudinal and transverse migration. The combination of both these effects made local particle concentrations lower near the mouth or nose regions of other occupants, at the expense of contaminating other rows. Between 19.5% and 27.4% of drops were removed through the outlet during the first 40 s and none of the droplets hit the mouth of the passengers. During their trajectory, the distance of drops to the mouth of the passengers was evaluated, showing that the majority of them passed at a relatively safe distance. However, a few of them passed at a close distance of the order of magnitude of 1 cm.
The marked magnitude and global scale of immunisation disruption evokes the dangers of vaccine-preventable disease outbreaks in the future. Trends indicating partial resumption of services highlight the urgent need for ongoing assessment of recovery, catch-up vaccination strategy implementation for vulnerable populations, and ensuring vaccine coverage equity and health system resilience.
Efficacy and safety of bamlanivimab may differ depending on whether an endogenous nAb response has been mounted. The limited sample size of the study does not allow firm conclusions based on these findings, and further independent trials are required that assess other types of passive immune therapies in the same patient setting.
December 20, 2021
We found waning vaccine protection of ChAdOx1 nCoV-19 against COVID-19 hospital admissions and deaths in both Scotland and Brazil, this becoming evident within three months of the second vaccine dose. Consideration needs to be given to providing booster vaccine doses for people who have received ChAdOx1 nCoV-19.
December 17, 2021
During fall 2021, 90 Lake County, Illinois, schools implemented Test to Stay (TTS), permitting eligible close contacts with masked COVID-19 exposures to remain in school. Secondary transmission among TTS participants was 1.5%; no tertiary transmission was observed among school-based contacts; however, tertiary cases were identified among household contacts. Implementation of TTS preserved up to 8,152 in-person learning days. Although vaccination remains the leading recommendation to protect against COVID-19, TTS allows close contacts to remain in the classroom as an alternative to home quarantine.
One in five LAC public schools adopted TTS. In TTS schools, student case rates did not increase, and tertiary transmission was not identified. A higher percentage of disadvantaged schools did not implement TTS. TTS does not appear to increase transmission risk in public schools and might greatly reduce loss of in-person school days. Implementation requires resources that might be currently unavailable for some schools. Vaccination remains the leading recommendation to protect against COVID-19; TTS allows students with a school exposure to remain in the classroom as an alternative to home quarantine.
Adults who reported a provider COVID-19 vaccination recommendation were more likely to have been vaccinated, to be concerned about COVID-19, to have confidence that COVID-19 vaccines are important and safe, and to perceive that family and friends had been vaccinated. A health care provider recommendation for COVID-19 vaccines at every visit could increase coverage and confidence in vaccines, particularly among groups with lower COVID-19 vaccination coverage, including younger adults, racial/ethnic minorities, and rural residents.
December 16, 2021
Report 49: Growth, population distribution and immune escape of Omicron in England
We find strong evidence of immune evasion, both from natural infection, where the risk of reinfection
is 5.41 (95% CI: 4.87-6.00) fold higher for Omicron than for Delta, and from vaccine-induced
protection. Our VE estimates largely agree with those from UKHSA’s TNCC study (11) and predictions
from predicting VE from neutralising antibody titres (4,14), suggesting very limited remaining
protection against symptomatic infection afforded by two doses of AZ, low protection afforded by two doses of Pfizer, but moderate to high (55-80%) protection in people boosted with an mRNA vaccine.
We find no evidence (for both risk of hospitalisation attendance and symptom status) of Omicron
having different severity from Delta, though data on hospitalisations are still very limited.
Our analysis reinforces the still emerging but increasingly clear picture that Omicron poses an
immediate and substantial threat to public health in England and more widely.
Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients
Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19.
Molnupiravir — A Step toward Orally Bioavailable Therapies for Covid-19
The Covid-19 pandemic has resulted in substantial global morbidity and mortality as well as disruption of the economies of virtually every country. Some of this tragedy could have been averted with the development of deliverable, orally bioavailable, direct-acting antiviral therapeutics. Molnupiravir, the orally bioavailable prodrug of N4-hydroxycytidine (NHC), begins to address this need.
Omicron blindspots: why it’s hard to track coronavirus variants
Researchers are racing to detect Omicron, the latest SARS-CoV-2 variant of concern, by sequencing the genomes of coronaviruses infecting people. But surveillance through genomic sequencing can be slow and patchy, complicating the picture of how and where Omicron spreads.
Modeling the onset of symptoms of COVID-19: Effects of SARS-CoV-2 variant
We developed a mathematical model to predict symptom order of symptomatic COVID-19 cases from patient characteristics data in the USA and China. Surprisingly, our model predicted that cough occurs first in the USA, while fever occurs first in China.
Understanding the burden of coronavirus disease (COVID-19) among children is essential for evidence-based decision-making regarding the vaccination of children and for assessing the importance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mitigation measures in specific settings, such as schools. Here, we report on the burden and severity of symptomatic notified COVID-19 cases among children in the European Union (EU)
December 15, 2021
A study led by researchers from the LKS Faculty of Medicine at The University of Hong Kong (HKUMed) provides the first information on how the novel Variant of Concern (VOC) of SARS-CoV-2, the Omicron SARS-CoV-2 infect human respiratory tract. The researchers found that Omicron SARS-CoV-2 infects and multiplies 70 times faster than the Delta variant and original SARS-CoV-2 in human bronchus, which may explain why Omicron may transmit faster between humans than previous variants. Their study also showed that the Omicron infection in the lung is significantly lower than the original SARS-CoV-2, which may be an indicator of lower disease severity. This research is currently under peer review for publication.
Booster of mRNA-1273 Vaccine Reduces SARS-CoV-2 Omicron Escape from Neutralizing Antibodies
The Omicron variant of SARS-CoV-2 is raising concerns because of its increased transmissibility and potential for reduced susceptibility to antibody neutralization. To assess the potential risk of this variant to existing vaccines, serum samples from mRNA-1273 vaccine recipients were tested for neutralizing activity against Omicron and compared to neutralization titers against D614G and Beta in a pseudovirus assay in two different laboratories. Omicron was 49-84-fold less sensitive to neutralization than D614G and 5.3-6.2-fold less sensitive than Beta when assayed with serum samples obtained 4 weeks after 2 standard inoculations with 100 µg mRNA-1273. A 50 µg boost increased Omicron neutralization titers and may substantially reduce the risk of symptomatic vaccine breakthrough infections.
In patients at high risk discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis.
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) showed susceptibility to diverse animal species. We conducted this study to understand the spatial epidemiology, genetic diversity, and statistically significant genetic similarity along with per-gene recombination events of SARS-CoV-2 and related viruses (SC2r-CoVs) in animals globally.
Universal Coronavirus Vaccines — An Urgent Need
The past 20 years have witnessed four fatal coronavirus outbreaks: SARS (severe acute respiratory syndrome, 2002 and 2003), MERS (Middle East respiratory syndrome, since 2012), and now Covid-19 (since 2019). Scientific evidence and ecologic reality suggest that coronaviruses will emerge again in the future, potentially posing an existential threat.
December 14, 2021
Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift
Here, we show that the Omicron RBD binds to human ACE2 with enhanced affinity relative to the Wuhan-Hu-1 RBD and acquires binding to mouse ACE2. Severe reductions of plasma neutralizing activity were observed against Omicron compared to the ancestral pseudovirus for vaccinated and convalescent individuals
Recent surveillance has revealed the emergence of the SARS-CoV-2 Omicron variant
(BA.1/B.1.1.529) harboring up to 36 mutations in spike protein, the target of vaccine-induced
neutralizing antibodies. Given its potential to escape vaccine-induced humoral immunity, we
measured neutralization potency of sera from 88 mRNA-1273, 111 BNT162b, and 40
Ad26.COV2.S vaccine recipients against wild type, Delta, and Omicron SARS-CoV-2
pseudoviruses. We included individuals that were vaccinated recently (<3 months), distantly (6-
12 months), or recently boosted, and accounted for prior SARS-CoV-2 infection. Remarkably,
neutralization of Omicron was undetectable in most vaccinated individuals. However, individuals
boosted with mRNA vaccines exhibited potent neutralization of Omicron only 4-6-fold lower than
wild type, suggesting that boosters enhance the cross-reactivity of neutralizing antibody
responses. In addition, we find Omicron pseudovirus is more infectious than any other variant
tested. Overall, this study highlights the importance of boosters to broaden neutralizing antibody
responses against highly divergent SARS-CoV-2 variants.
We found increased risks of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines and the first and second doses of the mRNA-1273 vaccine over the 1–28 days postvaccination period, and after a SARS-CoV-2 positive test. We estimated an extra two (95% confidence interval (CI) 0, 3), one (95% CI 0, 2) and six (95% CI 2, 8) myocarditis events per 1 million people vaccinated with ChAdOx1, BNT162b2 and mRNA-1273, respectively, in the 28 days following a first dose and an extra ten (95% CI 7, 11) myocarditis events per 1 million vaccinated in the 28 days after a second dose of mRNA-1273. This compares with an extra 40 (95% CI 38, 41) myocarditis events per 1 million patients in the 28 days following a SARS-CoV-2 positive test. We also observed increased risks of pericarditis and cardiac arrhythmias following a positive SARS-CoV-2 test. Similar associations were not observed with any of the COVID-19 vaccines, apart from an increased risk of arrhythmia following a second dose of mRNA-1273.
The Omicron variant of SARS-CoV-2 was first identified in Southern Africa during November 2021. It was brought to the world’s attention by scientists in South Africa and Botswana and declared a Variant of Concern by the World Health Organization shortly thereafter. South Africa experienced rapid community spread (concentrated in the Gauteng), dominated by the Omicron variant, fuelling South Africa’s fourth wave of COVID-19.
Latest on Omicron Variant and COVID-19 Vaccine Protection
There’s been great concern about the new Omicron variant of SARS-CoV-2, the coronavirus that causes COVID-19. A major reason is Omicron has accumulated over 50 mutations, including about 30 in the spike protein, the part of the coronavirus that mRNA vaccines teach our immune systems to attack. All of these genetic changes raise the possibility that Omicron could cause breakthrough infections in people who’ve already received a Pfizer or Moderna mRNA vaccine.
December 13, 2021
COVID-19 certification led to increased vaccinations 20 days before implementation in anticipation, with a lasting effect up to 40 days after. Countries with pre-intervention uptake that was below average had a more pronounced increase in daily vaccinations compared with those where uptake was already average or higher. In France, doses exceeded 55 672 (95% CI 49 668–73 707) vaccines per million population or, in absolute terms, 3 761 440 (3 355 761–4 979 952) doses before mandatory certification and 72 151 (37 940–114 140) per million population after certification (4 874 857 [2 563 396–7 711 769] doses). We found no effect in countries that already had average uptake (Germany), or an unclear effect when certificates were introduced during a period of limited vaccine supply (Denmark). Increase in uptake was highest for people younger than 30 years after the introduction of certification. Access restrictions linked to certain settings (nightclubs and events with >1000 people) were associated with increased uptake in those younger than 20 years. When certification was extended to broader settings, uptake remained high in the youngest group, but increases were also observed in those aged 30–49 years.
As health-care professionals and researchers worldwide continue to warn of the complications of COVID-19 on cancer, a new US-based study has now further highlighted the link between the pandemic and worsening cancer care. The time-frame study published on Dec 6, 2021, included the pre-pandemic phase and the primary surge of COVID-19 infections.
December 11, 2021
High-dose budesonide for early COVID-19
We were encouraged by the results of the PRINCIPLE trial, which in vulnerable individuals showed inhaled budesonide to confer a non-significant –25% (95% CI –45 to 3) relative reduction in the composite coprimary endpoint of hospital admission or death, with the number needed to treat being 50. Notably, the study had 90% power to detect a 50% reduction in the composite endpoint. The investigators appear to have attributed any protective effects of budesonide to its local glucocorticoid activity in the lung.
High-dose budesonide for early COVID-19
It is important to understand the illness severity of the study population, such as how many participants were symptomatic versus asymptomatic at enrolment, how many were compliant with treatment versus non-adherent, and if there were any outcome differences among them. We are curious if time from enrolment to treatment initiation differed among participants. The Article's Table 1 includes 833 participants from the inhaled budesonide group and 1126 participants from the usual care group, respectively, which does not coincide with the 787 and 1069 included for primary analysis.
December 10, 2021
These findings from a cohort of older, hospitalized veterans with high prevalences of underlying conditions suggest the importance of booster doses to help maintain long-term protection against severe COVID-19.
Community-Based Testing Sites for SARS-CoV-2 — United States, March 2020–November 2021
The CBTS program demonstrated the value of successful partnerships and collaboration for providing testing services that are responsive to local community needs. These lessons can guide current community-based screening, surveillance, and disease control programs and responses to future public health emergencies.
SARS-CoV-2 B.1.1.529 (Omicron) Variant — United States, December 1–8, 2021
During December 1–8, 2021, 22 U.S. states reported at least one COVID-19 case attributed to the Omicron variant. Among 43 cases with initial follow-up, one hospitalization and no deaths were reported. Implementation of concurrent prevention strategies, including vaccination, masking, improving ventilation, testing, quarantine, and isolation are recommended to slow transmission of SARS-CoV-2, including variants such as Omicron, to protect against severe illness and death from COVID-19.
During August 13–November 19, 2021, 18.7 million persons aged ≥65 years received a booster or additional primary dose of COVID-19 vaccine, constituting 44.1% of eligible persons aged ≥65 years. Coverage differed by primary series vaccine product and race/ethnicity. Strategic efforts are needed to encourage eligible persons aged ≥18 years, especially those aged ≥65 years and those who are immunocompromised, to receive a booster and/or additional primary dose to ensure maximal protection against COVID-19.
Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern
Our findings indicate that 2 doses of vaccination with BNT162b2 or ChAdOx1 are insufficient to give adequate levels of protection against infection and mild disease with the Omicron variant, although we cannot comment on protection against severe disease. Booster doses of BNT162b2 provide a significant increase in protection against mild disease and are likely to offer even greater levels of protection against severe disease. As such our findings support maximising coverage with third doses of vaccine in highly vaccinated populations such as the UK. Further follow-up will be needed to assess the duration of protection of booster vaccination.
December 9, 2021
Audio Interview: Waning Immunity against SARS-CoV-2
In this audio interview conducted on December 7, 2021, the editors discuss new studies of the duration of immunity conferred by Covid-19 vaccines.
Emerging SARS-CoV-2 variants: shooting the messenger
On Nov 24, South Africa alerted the world to the latest SARS-CoV-2 variant, omicron (B.1.1.529). The omicron variant distinguishes itself from previous variants by harbouring in its genomic sequence 49 mutations (30 of which occur within the spike protein)—a jump from the 13 mutations found within the delta variant (B.1.617.2). More mutations does not intrinsically mean that a variant is more dangerous, but almost immediately omicron generated concern within the global health community regarding its transmissibility and ability to evade both vaccine-induced and natural immunity. The report of the new variant has caused national governments to react with the reintroduction of non-pharmaceutical measures and ramped up vaccine booster programmes in the hope of delaying the spread of omicron. Controversially, however, for some governments the immediate response was to issue travel bans against South Africa. The UK was the first to adopt such a proposal, and was swiftly followed by the USA, Israel, and others.
December 8, 2021
Reduced Neutralization of SARS-CoV-2 Omicron Variant by Vaccine Sera and monoclonal antibodies
Since SARS-CoV-2 Omicron was resistant to casirivimab and imdevimab genotyping of SARS-CoV-2 may be needed before initiating mAb treatment. Variant-specific vaccines and mAb agents may be required to treat Omicron and other emerging variants of concern.
Omicron likely to weaken COVID vaccine protection
But the preliminary results — released overnight by teams in South Africa, Germany, and Sweden, as well as the Pfizer-BioNtech collaboration — hint that protection conferred by existing COVID-19 vaccines won’t be totally wiped out, and that boosters should improve immunity to Omicron.
BNT162b2 Vaccine Booster and Mortality Due to Covid-19
Participants who received a booster at least 5 months after a second dose of BNT162b2 had 90% lower mortality due to Covid-19 than participants who did not receive a booster.
Protection against Covid-19 by BNT162b2 Booster across Age Groups
Across the age groups studied, rates of confirmed Covid-19 and severe illness were substantially lower among participants who received a booster dose of the BNT162b2 vaccine than among those who did not.
More than 10.7 million undocumented immigrants and 8 million citizens with at least 1 undocumented family member live in the US. Evidence shows that immigrants are at increased risk for COVID-19 infection and have high levels of distrust in public systems. Contact tracing is an effective way to mitigate disease transmission but requires trust and cooperation among infected persons and their contacts. Using the Centers for Disease Control and Prevention sample contact tracing script as a framework, we describe undocumented immigrants’ attitudes about contact tracing and challenges that may be a factor in their ability to follow contact tracing and public health guidelines.
These findings suggest that health systems learned to adapt and were able to self-regulate, maintaining surgical procedure volume during the largest peak in volume of patients with COVID-19.
December 7, 2021
International risk of SARS-CoV-2 Omicron variant importations originating in South Africa
Omicron, a fast-spreading SARS-CoV-2 variant of concern reported to the World Health Organization on November 24, 2021, has raised international alarm. We estimated there is at least 50% chance that Omicron had been introduced by travelers from South Africa into all of the 30 countries studied by November 27, 2021.
A Randomized Clinical Trial
Among patients with severe COVID-19, treatment with high-flow oxygen therapy compared with conventional oxygen therapy reduced the likelihood of invasive mechanical ventilation and decreased time to clinical recovery.
December 6, 2021
S glycoprotein diversity of the Omicron variant
On the backdrop of ongoing Delta variant infection and vaccine-induced immunity, the emergence of the new Variant of Concern, the Omicron, has again fuelled the fears of COVID-19 around the world. Currently, very little information is available about the S glycoprotein mutations, transmissibility, severity, and immune evasion behaviour of the Omicron variant. In the present study, we have performed a comprehensive analysis of the S glycoprotein mutations of 309 strains of the Omicron variant and also discussed the probable effects of observed mutations on several aspects of virus biology based on known available knowledge of mutational effects on S glycoprotein structure, function, and immune evasion characteristics.
Omicron Has Reached the US—Here’s What Infectious Disease Experts Know About the Variant
On December 1, JAMA convened a panel of experts to discuss what’s known—and unknown—about Omicron, the newest SARS-CoV-2 variant of concern.
Intention to Vaccinate Children Against COVID-19 Among Vaccinated and Unvaccinated US Parents
In September 2021, one-fourth of the COVID-19 cases in the US were among children. Vaccinating children against COVID-19 is the most effective way to reduce disease burden and ensure safe return to in-person schooling and other social activities. National surveys show hesitancy among parents to vaccinate children, even when they are vaccinated themselves. We measured parental intention to vaccinate children and related sociodemographic factors in a national sample of US parents.
December 5, 2021
Ad26.COV2.S or BNT162b2 Boosting of BNT162b2 Vaccinated Individuals
Previous studies have reported that a third dose of the BNT162b2 (Pfizer) COVID-19 vaccine increased antibody titers and protective efficacy. Here we compare humoral and cellular immune responses in 65 individuals who were vaccinated with the BNT162b2 vaccine and were boosted after at least 6 months with either Ad26.COV2.S (Johnson & Johnson; N=41) or BNT162b2 (Pfizer; N=24).
December 3, 2021
COVID-19 outbreaks have been reported in homeless shelters across the United States. Many persons experiencing homelessness are older adults or persons with underlying medical conditions, placing them at increased risk for severe COVID-19–associated illness. The proportion of persons experiencing homelessness who are fully vaccinated against COVID-19 in the United States is currently unknown. Many persons experiencing homelessness express a willingness to receive the COVID-19 vaccine.
Immunogenicity of Extended mRNA SARS-CoV-2 Vaccine Dosing Intervals
Standard dosing intervals for BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines are 21 and 28 days, respectively.1 Data suggest improved effectiveness of ChAdOx1 adenoviral2 and other nonreplicating vaccines3 with increased dosing intervals, but little data exist for mRNA vaccines. This study investigated the immunogenicity of extended mRNA vaccine dosing intervals.
Data Emerge From the UK’s COVID-19 Vaccine Extended Dosing Interval
Late last year, UK health authorities announced that the second dose of authorized COVID-19 vaccines would be administered up to 12 weeks instead of 3 to 4 weeks after the first dose. The change was intended to free up initial doses for more people, but it also created an opportunity to investigate a vaccine schedule that hadn’t been tested in clinical trials.
December 2, 2021
Population-level evidence suggests that the Omicron variant is associated with substantial ability to evade immunity from prior infection. In contrast, there is no population-wide epidemiological evidence of immune escape associated with the Beta or Delta variants. This finding has important implications for public health planning, particularly in countries like South Africa with high rates of immunity from prior infection. Urgent questions remain regarding whether Omicron is also able to evade vaccine-induced immunity and the potential implications of reduced immunity to infection on protection against severe disease and death.
Tajima D test accurately forecasts Omicron / COVID-19 outbreak
On 26 November 2021, the World Health Organization designated the SARS-CoV-2 variant B.1.1.529, Omicron, a variant of concern. However, the phylogenetic and evolutionary dynamics of this variant remain unclear. An analysis of the 131 Omicron variant sequences from November 9 to November 28, 2021 reveals that variants have diverged into at least 6 major subgroups. 86.3% of the cases have an insertion at amino acid 214 (INS214EPE) of the spike protein.
US State-Level Legal Interventions Related to COVID-19 Vaccine Mandates
Mandates can increase vaccine uptake, but their effectiveness is associated with who is covered, penalties, and exemptions. The US federal government recently required federal employees to be vaccinated against SARS-CoV-2 and developed standards for large employers. However, individual states traditionally take the lead in regulating public health via vaccine mandates. Some states have attempted to introduce requirements to increase uptake of COVID-19 vaccines. However, others have attempted to impede COVID-19 vaccine mandates. Most efforts have been considered by legislatures; also, some governors and regulatory agencies have issued executive orders. We assessed state-level legal interventions to promote or impede COVID-19 vaccine mandates since the beginning of the pandemic.
December 1, 2021
Comparative Effectiveness of BNT162b2 and mRNA-1273 Vaccines in U.S. Veterans
The 24-week risk of Covid-19 outcomes was low after vaccination with mRNA-1273 or BNT162b2, although risks were lower with mRNA-1273 than with BNT162b2. This pattern was consistent across periods marked by alpha- and delta-variant predominance.
Covid-19 Vaccine Effectiveness in New York State
The effectiveness of the three vaccines against Covid-19 declined after the delta variant became predominant. The effectiveness against hospitalization remained high, with modest declines limited to BNT162b2 and mRNA-1273 recipients 65 years of age or older.
Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalised patients with COVID-19, with a safety profile similar to that of placebo. The added value of lenzilumab beyond other immunomodulators used to treat COVID-19 alongside steroids remains unknown.
SARS-CoV-2 reinfections were rare in older residents and younger staff. Protection from SARS-CoV-2 was sustained for longer than 9 months, including against the alpha variant. Reinfection was associated with no or low neutralising antibody before reinfection, but significant boosting occurred on reinfection.
In this cross-sectional study of 12 610 HCP at a major US academic hospital, two-thirds received a first dose within the first 4 months; 98% of those received 2 doses. Adjusted for age, sex, job position, and area-level social vulnerability, Black or African American and multiracial HCP were less likely to receive the vaccine compared with White HCP, with narrower disparities observed for nurses and no disparities found among physicians.
Assessment of Patient Preferences for Telehealth in Post–COVID-19 Pandemic Health Care
In this survey study of 2080 adults, most respondents were willing to use video visits in the future but, when presented with the choice between an in-person or a video visit for nonemergency care, most preferred in-person care. Willingness to pay for preferred visit modality was higher for those who preferred in-person care, and those who preferred video visits were more sensitive to out-of-pocket cost.
Stimulating severe COVID-19: the potential role of GM-CSF antagonism
Over the past 20 months of the COVID-19 pandemic, a great deal has been crystallised about the ideal therapeutic targets for infected patients. For very sick patients who require hospitalisation, we now know that targeting the dysregulated host response is of greater value than targeting the virus. Through steroids, interleukin(IL)-6 blockade, IL-1 blockade, tyrosine kinase inhibition, or Janus kinase inhibition, we have a breadth of clinical trials that show the possible mortality benefits of both broad and focused immunomodulation in severely ill patients with COVID-19. As the pandemic continues, there is a need to understand whether combinations or different agents that target alternative pathways would continue to improve clinical outcomes, or whether there are ways of identifying specific patients with a higher likelihood of benefit from specific therapies.
Covid-19 mRNA Vaccines — Six of One, Half a Dozen of the Other
In many countries, the availability of vaccines has marked a turning point in the Covid-19 pandemic. Although the vaccines are imperfect, breakthrough infections in fully vaccinated people remain quite rare, even with recently emerging variants. Countries with high vaccination rates have largely been able to reopen, and rates of severe illness and death have dropped dramatically. But this has not been a smooth process.
Viral Dynamics of SARS-CoV-2 Variants in Vaccinated and Unvaccinated Persons
Two opposing forces that are shaping the coronavirus disease 2019 (Covid-19) pandemic are the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern and the uptake of vaccines. Measurement of SARS-CoV-2 viral load over the course of acute infection can inform hypotheses about the mechanisms that underlie variation in transmissibility according to variant and vaccination status.
Therapeutic implications of ongoing alveolar viral replication in COVID-19
In patients with moderate-to-severe COVID-19 pneumonia, an aberrant post-viral alveolitis with excessive inflammatory responses and immunothrombosis underpins use of immunomodulatory therapy (eg, corticosteroids and interleukin-6 receptor antagonism). By contrast, immunosuppression in individuals with mild COVID-19 who do not require oxygen therapy or in those with critical disease undergoing prolonged ventilation is of no proven benefit.
COVID-19 wastewater epidemiology: a model to estimate infected populations
The SEIR model provides a robust method to estimate the total number of infected individuals in a sewershed on the basis of the mass rate of RNA copies released per day. This approach overcomes some of the limitations associated with individual testing campaigns and thereby provides an additional tool that can be used to inform policy decisions.
November 30, 2021
In this case-control study that included 306 710 Israeli adults 40 years and older, there was an estimated significant reduction in the odds of SARS-CoV-2 infection within a few weeks of receiving the booster compared with receiving just the 2 primary doses. Those receiving the booster also had lower odds of hospitalization.
November 29, 2021
In this randomized clinical trial of 487 patients with COVID-19 pneumonia and a partial pressure of arterial oxygen–to–fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg at enrollment, the rate of the primary clinical end point (need for mechanical ventilation, defined as Pao2/Fio2 ratio <150 mm Hg, or death) was not significantly different between the convalescent plasma group and the control group.
November 26, 2021
Analyses of patients have revealed marked dysregulation of the immune system in severe cases of human coronavirus infection, and there is ample evidence that aberrant immune responses to human coronaviruses are typified by impaired induction of interferons, exuberant inflammatory responses and delayed adaptive immune responses. In addition, various viral proteins have been shown to impair interferon induction and signalling and to induce inflammasome activation. This suggests that severe disease associated with human coronaviruses is mediated by both dysregulated host immune responses and active viral interference. Here we discuss our current understanding of the mechanisms involved in each of these scenarios.
Participation in a large, indoor, live gathering without physical distancing was not associated with increased SARS-CoV-2–transmission risk, provided a comprehensive preventive intervention was implemented.
November 25, 2021
The ChAdOx1 nCoV-19 vaccine remained effective against moderate-to-severe COVID-19, even during a surge that was dominated by the highly transmissible delta variant of SARS-CoV-2. Spike-specific T-cell responses were maintained against the delta variant. Such cellular immune protection might compensate for waning humoral immunity.
The emergence of powerful oral anti-COVID-19 drugs in the post-vaccine era
The quest for effective drugs to treat COVID-19 has been a priority since the outbreak of the disease. The clinical application of remdesivir has been greatly restricted by the need for intravenous administration, as well as unstable concentrations in plasma and variable antiviral activity in different organelles.
November 24, 2021
Severity of SARS-CoV-2 Reinfections as Compared with Primary Infections
Qatar had a first wave of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March through June 2020, after which approximately 40% of the population had detectable antibodies against SARS-CoV-2.
In this case series study, our findings were similar to those of the study by Alejo et al,5 in which a fourth dose of SARS-CoV-2 vaccine was associated with slightly improved humoral response among patients with a weak response after 3 doses and with no improvement among those with no response after 3 doses. Neutralizing antibody titers and cellular response were low in both groups.
Moral injury can result from chronic stressors in morally injurious environments; leadership must identify and address these stressors to effectively support health care professionals as COVID-19 continues to strain staff’s physical, mental, and emotional resources.
A Possible Role for Anti-idiotype Antibodies in SARS-CoV-2 Infection and Vaccination
he pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is incompletely understood, with its effects on multiple organ systems and the syndrome of “long Covid” occurring long after the resolution of infection. The development of multiple efficacious vaccines has been critical in the control of the pandemic, but their efficacy has been limited by the appearance of viral variants, and the vaccines can be associated with rare off-target or toxic effects, including allergic reactions, myocarditis, and immune-mediated thrombosis and thrombocytopenia in some healthy adults. Many of these phenomena are likely to be immune-mediated.
November 19, 2021
Among 1,249,634 delivery hospitalizations during March 2020–September 2021, U.S. women with COVID-19 were at increased risk for stillbirth compared with women without COVID-19 (adjusted relative risk [aRR] = 1.90; 95% CI = 1.69–2.15). The magnitude of association was higher during the period of SARS-CoV-2 B.1.617.2 (Delta) variant predominance than during the pre-Delta period. Implementing evidence-based COVID-19 prevention strategies, including vaccination before or during pregnancy, is critical to reduce the impact of COVID-19 on stillbirths.
Pregnant and recently pregnant women are at increased risk for severe illness and death from COVID-19 compared with women who are not pregnant or were not recently pregnant. CDC recommends COVID-19 vaccination for women who are pregnant, recently pregnant, trying to become pregnant, or might become pregnant in the future.
Among persons aged ≥12 years enrolled in a Pacific Northwest health plan, unvaccinated persons with SARS-CoV-2 infection were approximately twice as likely to receive ED care or to be hospitalized than were vaccinated persons with COVID-19. The findings in this report support CDC’s current recommendation that all persons aged ≥5 years should receive full COVID-19 vaccination, including additional and booster doses, to prevent illness and reduce transmission of SARS-CoV-2.
Among adults with diabetes, those aged 18–29 years reported the most disruption in access to and use of medical care and the least engagement in prevention of COVID-19, including vaccination intent. Efforts are warranted to enhance access to diabetes care during the COVID-19 pandemic, and to deliver public health messages emphasizing the importance of diabetes management and COVID-19 prevention, including vaccination, especially among younger adults with diabetes.
Overall, 56% of patients with a positive SARS-CoV-2 test result were notified by telephone call or digital notification within 24 hours of report in January 2021, compared with 15% during November 23–December 23, 2020. Differences in text notification by age, race, and ethnicity were observed. Automated digital notification can provide a more timely means for reaching persons with COVID-19 and can likely facilitate more rapid patient isolation and increase efficiency of case investigation.
The conditions of hospital strain during July 2020–July 2021, which included the presence of SARS-CoV-2 B.1.617.2 (Delta) variant, predicted that intensive care unit bed use at 75% capacity is associated with an estimated additional 12,000 excess deaths 2 weeks later. As hospitals exceed 100% ICU bed capacity, 80,000 excess deaths would be expected 2 weeks later.
November 18, 2021
Early Convalescent Plasma for High-Risk Outpatients with Covid-19
The administration of Covid-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of Covid-19 did not prevent disease progression.
The overall risk for severe COVID-19 among WRA remains low; however, symptomatic pregnant WRA remain at increased risk for severe outcomes compared with symptomatic nonpregnant WRA during Delta variant predominance. Compared with the pre-Delta period, pregnant and nonpregnant WRA are at increased risk for severe COVID-19 in the Delta period.
Population impact of SARS-CoV-2 variants with enhanced transmissibility and/or partial immune escape
SARS-CoV-2 variants of concern exhibit varying degrees of transmissibility and, in some cases, escape from acquired immunity. Much effort has been devoted to measuring these phenotypes, but understanding their impact on the course of the pandemic – especially that of immune escape – has remained a challenge. Here, we use a mathematical model to simulate the dynamics of wildtype and variant strains of SARS-CoV-2 in the context of vaccine rollout and nonpharmaceutical interventions. We show that variants with enhanced transmissibility frequently increase epidemic severity, whereas those with partial immune escape either fail to spread widely, or primarily cause reinfections and breakthrough infections. However, when these phenotypes are combined, a variant can continue spreading even as immunity builds up in the population, limiting the impact of vaccination and exacerbating the epidemic. These findings help explain the trajectories of past and present SARS-CoV-2 variants and may inform variant assessment and response in the future.
Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin
The struggle to control the COVID-19 pandemic is made challenging by the emergence of virulent SARS-CoV-2 variants. To gain insight into their replication dynamics, emergent Alpha (A), Beta (B) and Delta (D) SARS-CoV-2 variants were assessed for their infection performance in single variant- and co-infections. The effectiveness of thapsigargin (TG), a recently discovered broad-spectrum antiviral, against these variants was also examined. Of the 3 viruses, the D variant exhibited the highest replication rate and was most able to spread to in-contact cells; its replication rate at 24 h post-infection (hpi) based on progeny viral RNA production was over 4 times that of variant A and 9 times more than the B variant. In co-infections, the D variant boosted the replication of its co-infected partners at the expense of its own initial performance. Furthermore, co-infection with AD or AB combination conferred replication synergy where total progeny (RNA) output was greater than the sum of corresponding single-variant infections. All variants were highly sensitive to TG inhibition.
This systematic review and meta-analysis suggests that several personal protective and social measures, including handwashing, mask wearing, and physical distancing are associated with reductions in the incidence covid-19. Public health efforts to implement public health measures should consider community health and sociocultural needs, and future research is needed to better understand the effectiveness of public health measures in the context of covid-19 vaccination.
November 17, 2021
The analysis suggests that the relative protection of the booster shot against infection is likely to be significantly smaller than the initial estimates of 10-11-fold (over 90%) reported by the MOH, probably around 60% at best. This also implies that the absolute number of infected individuals in the Vaccinated group is likely to be at least as high as in the Unvaccinated, raising serious concerns that the new Green Pass is inefficient in preventing infection spread, and could expose high risk individuals to risk.
November 15, 2021
In a large, multicenter, retrospective cohort study of 83 584 patients with laboratory-confirmed COVID-19 who had an emergency department or urgent care visit or were admitted for observation or hospitalized across 87 health care centers in the US, Oskotsky et al observed an association between selective serotonin reuptake inhibitor (SSRI) administration and reduced mortality in 3401 patients with COVID-19 compared with 6802 matched control patients who were not given SSRIs but shared similar sociodemographic characteristics, medical comorbidities, and medication indication.
Long Covid after Breakthrough COVID-19: the post-acute sequelae of breakthrough COVID-19
Altogether, our findings show increased risks of death and post-acute sequalae in people with breakthrough COVID-19; the risks are evident among those who were not hospitalized during the acute phase of the disease. Our comparative approach provides context for understanding the risks in relation to COVID-19 without prior vaccination and seasonal influenza. The findings will inform the ongoing effort to optimize strategies for prevention of breakthrough SARS-CoV-2 infections and will guide development and optimization of post-acute care pathways for people with breakthrough COVID-19.
Maternal COVID-19 leaves a lasting immunological impression on the fetus
In summary, these new data show that fetal exposure to SARS-CoV-2 acutely increases the frequencies of fetal NK cell and γδ T cell immune effector cells, and also accelerates the maturation and non-specific activation of multiple fetal immune cell populations. Although the effect of these changes on neonatal immunity might not be known for many years, fetal exposure to a maternal SARS-CoV-2 infection — even in the absence of a congenital infection — can imprint the fetal immune system.
November 12, 2021
On November 2, 2021, after a systematic review of available data, the Advisory Committee on Immunization Practices made an interim recommendation for use of the Pfizer-BioNTech COVID-19 vaccine in children aged 5–11 years in the United States for prevention of COVID-19. The Pfizer-BioNTech COVID-19 vaccine has high efficacy (>90%) against COVID-19 in children aged 5–11 years, and benefits outweigh risks for vaccination. Vaccination is important to protect children against COVID-19 and reduce community transmission of SARS-CoV-2.
November 5, 2021
On November 2, 2021, after a systematic review of available data, the Advisory Committee on Immunization Practices made an interim recommendation for use of the Pfizer-BioNTech COVID-19 vaccine in children aged 5–11 years in the United States for prevention of COVID-19. The Pfizer-BioNTech COVID-19 vaccine has high efficacy (>90%) against COVID-19 in children aged 5–11 years, and benefits outweigh risks for vaccination. Vaccination is important to protect children against COVID-19 and reduce community transmission of SARS-CoV-2.
November 2, 2021
Effectiveness of mRNA vaccination against laboratory-confirmed COVID-19–associated hospitalization was lower (77%) among immunocompromised adults than among immunocompetent adults (90%). Vaccine effectiveness varied considerably among immunocompromised patient subgroups. Immunocompromised persons benefit from COVID-19 mRNA vaccination but are less protected from severe COVID-19 outcomes than are immunocompetent persons. Immunocompromised persons receiving mRNA COVID-19 vaccines should receive 3 doses and a booster, consistent with CDC recommendations, practice nonpharmaceutical interventions, and, if infected, be monitored closely and considered early for proven therapies that can prevent severe outcomes.
October 29, 2021
Among COVID-19–like illness hospitalizations among adults aged ≥18 years whose previous infection or vaccination occurred 90–179 days earlier, the adjusted odds of laboratory-confirmed COVID-19 among unvaccinated adults with previous SARS-CoV-2 infection were 5.49-fold higher than the odds among fully vaccinated recipients of an mRNA COVID-19 vaccine who had no previous documented infection (95% confidence interval = 2.75–10.99). All eligible persons should be vaccinated against COVID-19 as soon as possible, including unvaccinated persons previously infected with SARS-CoV-2.
The Advisory Committee on Immunization Practices issued recommendations for an additional primary mRNA COVID-19 vaccine dose for immunocompromised persons and a COVID-19 vaccine booster dose in eligible groups. Health care professionals play a critical role in COVID-19 vaccination efforts, including for primary, additional primary, and booster vaccination, particularly to protect patients who are at increased risk for severe illness and death.
Detection of SARS-CoV-2 by rapid antigen tests on saliva in hospitalized patients with COVID-19
Our study therefore supports saliva testing as an alternative diagnostic procedure to NPH testing, and that rapid antigen test on saliva provides a potential complement to PCR test to meet increasing screening demand.
Vaccination reduces the risk of delta variant infection and accelerates viral clearance. Nonetheless, fully vaccinated individuals with breakthrough infections have peak viral load similar to unvaccinated cases and can efficiently transmit infection in household settings, including to fully vaccinated contacts. Host–virus interactions early in infection may shape the entire viral trajectory.
October 27, 2021
Treatment with fluvoxamine (100 mg twice daily for 10 days) among high-risk outpatients with early diagnosed COVID-19 reduced the need for hospitalisation defined as retention in a COVID-19 emergency setting or transfer to a tertiary hospital.
Invincibility threatens vaccination intentions during a pandemic
Our results suggest that despite the prevalence of personal feelings of invincibility across cultures, the effects of perceived invincibility on prosocial beliefs and behaviors depend on the extent to which individuals maintain an interdependent self-construal and feel responsible for the wellbeing of their community members. In turn, health communications should encourage a collectivistic mindset so as to promote prosocial beliefs and behaviors, despite personal feelings of invincibility. In the context of COVID-19, this is especially important in less collectivistic or individualistic cultures such as the U.S., U.K., and France.
Our findings show that the risk of a large wave of COVID-19 hospital admissions resulting from lifting NPIs can be substantially mitigated if the timing of NPI relaxation is carefully balanced against vaccination coverage. However, with the delta variant, it might not be possible to fully lift NPIs without a third wave of hospital admissions and deaths, even if vaccination coverage is high. Variants of concern, their transmissibility, vaccine uptake, and vaccine effectiveness must be carefully monitored as countries relax pandemic control measures.
What COVID vaccines for young kids could mean for the pandemic
“It will save lives in that age group,” says Emma McBryde, an infectious-diseases modeller at the Australian Institute of Tropical Health and Medicine in Townsville. But it could also have a broader impact, given that many US children aged 5 to 11 have returned to school unvaccinated in the past few months, and the group now accounts for a significant portion of new COVID-19 cases, capable of transmitting the coronavirus SARS-CoV-2 to others. “For every child’s life you save, you may well save many, many more adult lives,” she says.
October 26, 2021
Aspergillosis Is Common Among COVID-19 Patients in the ICU
Damage to the lining of airways from severe SARS-CoV-2 infection allows Aspergillus fungi to invade the tissue, according to a recent consensus guidance from the European Confederation of Medical Mycology and the International Society for Human and Animal Mycology. These secondary fungal infections can worsen patient outcomes, and they’ve raised concern about emerging evidence of Aspergillus resistance to voriconazole and isavuconazole, the first-line therapies.
October 25, 2021
Our work provides the first in vivo evidence of SARS-CoV-2 infection in human adipose tissue and describes the associated inflammation.
The findings of this cross-sectional study suggest that social gatherings among unvaccinated students were associated with increased COVID-19 infections (in this scenario, slowing the previous downward trend and briefly increasing) in a university’s community beginning 8 days after the event, which corresponds with the 75th percentile of time to symptom onset. This study identifies an urgent gap in evidence on the risk of COVID-19 spread at social gatherings among university students, although the increase in transmission was brief. This increase in transmission may have been brief because of increases in the vaccination rate of university students during this time or because some students may have completed their semester before the end of the study period.
October 22, 2021
During December 2020–July 2021, COVID-19 vaccine recipients had lower rates of non–COVID-19 mortality than did unvaccinated persons after adjusting for age, sex, race and ethnicity, and study site. There is no increased risk for mortality among COVID-19 vaccine recipients. This finding reinforces the safety profile of currently approved COVID-19 vaccines in the United States. All persons aged ≥12 years should receive a COVID-19 vaccine.
Analysis of COVID-NET data from 14 states found no significant increases in the proportion of hospitalized COVID-19 patients with severe outcomes during the Delta period. The proportion of hospitalized unvaccinated COVID-19 patients aged 18–49 years significantly increased during the Delta period. Lower vaccination coverage in adults aged 18–49 years likely contributed to the increase in hospitalized patients during the Delta period. COVID-19 vaccination is critical for all eligible adults, including adults aged <50 years who have relatively low vaccination rates compared with older adults.
Assessment of Cognitive Function in Patients After COVID-19 Infection
The association of COVID-19 with executive functioning raises key questions regarding patients’ long-term treatment. Future studies are needed to identify the risk factors and mechanisms underlying cognitive dysfunction as well as options for rehabilitation.
October 21, 2021
In this randomized trial that included 1000 patients with COVID-19 and severe hypoxemia, treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone. This difference was not statistically significant. Compared with 6 mg of dexamethasone, 12 mg of dexamethasone did not statistically significantly reduce the number of days alive without life support at 28 days.
October 19, 2021
Pregnancy influences immune responses to SARS-CoV-2
Infections during pregnancy contribute to high rates of maternal and fetal morbidity and mortality. However, the study of maternal-fetal immune responses to such infections remains underwhelming. The studies by Atyeo et al. and Bordt et al. on the immune responses to SARS-CoV-2 vaccination and infection demonstrate the critical nature of investigating maternal-fetal immune responses during pregnancy, a highly unique biological state. The findings of these studies have direct clinical implications for the COVID-19 pandemic and future maternal-fetal vaccination strategies, as they reveal that pregnant and lactating women have distinct immune responses to immunization and natural infection. Furthermore, these studies echo the call to action to incorporate women at different stages of gestation into clinical trials, thereby increasing their representation in the development of vaccines.
October 8, 2021
During March 4–July 21, 2021, sequencing data from 6,798 SARS-CoV-2–positive specimens were linked to electronic health records among Kaiser Permanente Southern California members. The weekly percentage of all infections attributed to the Delta variant rapidly increased to 95% during this period. Infection with the Delta variant was more common among younger persons and among non-Hispanic Black persons. These findings reinforce the importance of continued monitoring of SARS-CoV-2 variants and implementing multicomponent COVID-19 prevention strategies, particularly during the current period in which Delta is the predominant circulating variant in the United States.
October 7, 2021
Pan-Sarbecovirus Neutralizing Antibodies in BNT162b2-Immunized SARS-CoV-1 Survivors
Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern pose a challenge to the effectiveness of current vaccines. A vaccine that could prevent infection caused by known and future variants of concern as well as infection with pre-emergent sarbecoviruses (i.e., those with potential to cause disease in humans in the future) would be ideal. Here we provide data showing that potent cross-clade pan-sarbecovirus neutralizing antibodies are induced in survivors of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) infection who have been immunized with the BNT162b2 messenger RNA (mRNA) vaccine. The antibodies are high-level and broad-spectrum, capable of neutralizing not only known variants of concern but also sarbecoviruses that have been identified in bats and pangolins and that have the potential to cause human infection. These findings show the feasibility of a pan-sarbecovirus vaccine strategy.
Effectiveness of Covid-19 Vaccines in Ambulatory and Inpatient Care Settings
Covid-19 vaccines in the United States were highly effective against SARS-CoV-2 infection requiring hospitalization, ICU admission, or an emergency department or urgent care clinic visit. This vaccine effectiveness extended to populations that are disproportionately affected by SARS-CoV-2 infection.
Bamlanivimab plus Etesevimab in Mild or Moderate Covid-19
Among high-risk ambulatory patients, bamlanivimab plus etesevimab led to a lower incidence of Covid-19–related hospitalization and death than did placebo and accelerated the decline in the SARS-CoV-2 viral load.
COVID-19-Associated Orphanhood and Caregiver Death in the United States
We report overall and US state-specific findings, disaggregated by race/ethnicity, for COVID-19-associated orphanhood and death of grandparent caregivers. High rates of orphanhood, marked disparities, and state-specific differences show the overlooked burden among children at greatest risk, in states most affected.
October 6, 2021
Myocarditis after Covid-19 Vaccination in a Large Health Care Organization
Among patients in a large Israeli health care system who had received at least one dose of the BNT162b2 mRNA vaccine, the estimated incidence of myocarditis was 2.13 cases per 100,000 persons; the highest incidence was among male patients between the ages of 16 and 29 years. Most cases of myocarditis were mild or moderate in severity.
Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel
The incidence of myocarditis, although low, increased after the receipt of the BNT162b2 vaccine, particularly after the second dose among young male recipients. The clinical presentation of myocarditis after vaccination was usually mild.
Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months
Six months after receipt of the second dose of the BNT162b2 vaccine, humoral response was substantially decreased, especially among men, among persons 65 years of age or older, and among persons with immunosuppression.
Waning of BNT162b2 Vaccine Protection against SARS-CoV-2 Infection in Qatar
BNT162b2-induced protection against SARS-COV-2 infection appeared to wane rapidly following its peak after the second dose, but protection against hospitalization and death persisted at a robust level for 6 months after the second dose.
Real-world data show that filters clean COVID-causing virus from air
Research at a hospital swamped by people with COVID-19 has confirmed that portable air filters effectively remove SARS-CoV-2 particles from the air — the first such evidence in a real-world setting. The results suggest that air filters could be used to reduce the risk of patients and medical staff contracting SARS-CoV-2 in hospitals, the study’s authors say.
Given the association between disability and mortality involving COVID-19, verification of these findings and consideration of recommendations for protective measures are now required.
Coverage and Estimated Effectiveness of mRNA COVID-19 Vaccines Among US Veterans
In this case-control study including 6 647 733 veterans, 23% of veterans received at least 1 COVID-19 vaccination during the first 3 months of vaccine rollout. VE against infection was estimated to be 95% for full vaccination; estimated VE against COVID-19-related hospitalization was 91%, and there were no COVID-19–related deaths among fully vaccinated veterans.
COVID-19 incidence and standardized mortality rates remained consistently higher among the prison population than the overall US population in the first year of the pandemic. While COVID-19 incidence and mortality rates peaked in late 2020 and early 2021 and have since declined, the cumulative toll of COVID-19 has been several times greater among the prison population than the overall US population.
October 5, 2021
Nationwide, average anxiety severity scores increased 13% from August to December 2020 and then decreased 26.8% from December 2020 to June 2021. Similar increases and decreases occurred in depression severity scores.
Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include protected elective surgical pathways and long-term investment in surge capacity for acute care during public health emergencies to protect elective staff and services.
October 4, 2021
Our results provide support for high effectiveness of BNT162b2 against hospital admissions up until around 6 months after being fully vaccinated, even in the face of widespread dissemination of the delta variant. Reduction in vaccine effectiveness against SARS-CoV-2 infections over time is probably primarily due to waning immunity with time rather than the delta variant escaping vaccine protection.
Immunological responses to SARS-CoV-2 vaccines in kidney transplant recipients
Although the immune correlates of protection from disease have yet to be defined, we show markedly diminished humoral and cellular immune responses to both vector and mRNA SARS-CoV-2 vaccines in kidney transplant recipients. The planning of intervention studies to optimise vaccine platform and dosing are urgently required in this group, and preliminary reports suggest encouraging responses to third vaccine doses. In the interim, strategic planning to protect this susceptible population is required. This planning could include, but is not limited to, educating patients to maintain physical distancing rules and immunising household members, including prioritisation of children older than 12 years.
Effect of Convalescent Plasma on Organ Support–Free Days in Critically Ill Patients With COVID-19
This international bayesian randomized clinical trial that included 2011 participants treated with 2 units of high-titer convalescent plasma, compared with no convalescent plasma, resulted in a posterior probability of futility of 99.4% for the primary outcome of organ support–free days up to day 21.
October 1, 2021
The durability of immunity against reinfection by SARS-CoV-2: a comparative evolutionary study
These data provided a means to estimate profiles of the typical antibody decline and probabilities of reinfection over time under endemic conditions. Reinfection by SARS-CoV-2 under endemic conditions would likely occur between 3 months and 5·1 years after peak antibody response, with a median of 16 months. This protection is less than half the duration revealed for the endemic coronaviruses circulating among humans (5–95% quantiles 15 months to 10 years for HCoV-OC43, 31 months to 12 years for HCoV-NL63, and 16 months to 12 years for HCoV-229E). For SARS-CoV, the 5–95% quantiles were 4 months to 6 years, whereas the 95% quantiles for MERS-CoV were inconsistent by dataset.
COVID-19 Outbreaks at Youth Summer Camps — Louisiana, June–July 2021
The increased number of outbreaks and cases observed in Louisiana youth summer camps in 2021 compared with the previous year coincided with the widespread circulation of the highly transmissible Delta variant. This period also coincided with apparent underutilization of preventive measures such as vaccination, masking, and physical distancing. Multicomponent prevention measures, including vaccination of all eligible adults and adolescents, wearing masks indoors, regular screening testing, physical distancing and cohorting, and increasing ventilation can help prevent transmission of SARS-CoV-2 in settings with youths who cannot be vaccinated.
Implementation of high vaccination coverage coupled with multiple prevention strategies is critical to averting COVID-19 outbreaks in congregate settings, including overnight camps. These findings highlight important guiding principles for school and youth-based COVID-19 prevention protocols.
Analysis of the National Immunization Survey Adult COVID Module found that, compared with adults without a disability, those with a disability had a lower likelihood of having received COVID-19 vaccination, despite being less likely to report hesitancy about getting vaccinated. Adults with a disability reported more difficulties obtaining a COVID-19 vaccine than did persons without a disability.
September 30, 2021
In this cohort study of 901 samples from 595 patients with hematooncological diseases and a control group of health care workers, anti–SARS-CoV-2 spike antibodies after full immunization could be detected, although antibody levels were lower in patients than in health care workers. However, specific subgroups, such as patients who received B-cell–targeting therapy, showed impaired seroconversion. The study findings suggest that lower SARS-CoV-2 antibody levels in patients with cancer after vaccination compared with vaccinated health care workers, and particularly weak seroconversion in specific subgroups, highlight the need for dedicated vaccination trials in patients with cancer.
In this qualitative study, 70 participants from racial and ethnic minority communities in Los Angeles County described a complex vaccination decision-making process influenced by misinformation and politicization, deep apprehension related to historical inequity and mistreatment, access barriers related to social disadvantage, and a need for community engagement and trusted messengers. This study suggests that COVID-19 vaccine equity will require multifaceted policies and programming that respect community concerns and the need for informed deliberation, invest in community-based engagement, improve accessibility and transparency of information, and reduce structural barriers in vaccination.
Assessment of Communication Strategies for Mitigating COVID-19 Vaccine-Specific Hesitancy in Canada
In a between-participants survey study of adult Canadian citizens, individuals who were provided information on the death prevention potential of less-preferred vaccines, such as AstraZeneca and Johnson & Johnson, reported more confidence in their effectiveness and a higher likelihood of taking these vaccines if offered compared with those who did not receive this information. Information on the overall effectiveness of these vaccines at preventing symptomatic COVID-19 showed the opposite result. These findings suggest that communication strategies that focus on the death prevention potential of less-preferred COVID-19 vaccines have the potential to improve their uptake, whereas focusing on such metrics as their comparatively less impressive overall effectiveness at preventing symptomatic COVID-19 could undermine these efforts.
Our most notable finding was no difference in adherence rates for patients without diabetes who had telemedicine encounters. This demonstrates the benefit of telemedicine in preventive care—comparable quality with lower cost. Similar to recent literature, during the pandemic, telemedicine met a care demand in our study; but moving forward, telemedicine may be a valuable care venue, especially in primary care.
September 29, 2021
REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19
REGEN-COV reduced the risk of Covid-19–related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo.
Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine
AZD1222 was safe and efficacious in preventing symptomatic and severe Covid-19 across diverse populations that included older adults.
COVID-19 hospitalisations and deaths were uncommon 14 days or more after the first vaccine dose in this national analysis in the context of a high background incidence of SARS-CoV-2 infection and with extensive social distancing measures in place. Sociodemographic and clinical features known to increase the risk of severe disease in unvaccinated populations were also associated with severe outcomes in people receiving their first dose of vaccine and could help inform case management and future vaccine policy formulation.
This study reported prolonged symptoms of COVID-19 and found that severe disease during hospitalization was a risk factor for more symptoms and higher chronic obstructive pulmonary disease assessment test scores.
September 28, 2021
During August 12–September 19, 2021, among 12,591 v-safe registrants who completed a health check-in survey after all 3 doses of an mRNA COVID-19 vaccine, 79.4% and 74.1% reported local or systemic reactions, respectively, after the third dose; 77.6% and 76.5% reported local or systemic reactions after the second dose, respectively. Voluntary reports to v-safe found no unexpected patterns of adverse reactions after an additional dose of COVID-19 vaccine. CDC will continue to monitor vaccine safety, including for additional COVID-19 doses.
Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity.
In this survey study of adults living in a large US city, consistent masking was associated with a decrease in SARS-CoV-2 acquisition; however, Hispanic individuals were at higher risk for infection, more often worked outside the home, and were less likely to have received economic aid through stimulus checks or unemployment benefits.
September 24, 2021
CDC Statement on ACIP Booster Recommendations
Today, CDC Director Rochelle P. Walensky, M.D., M.P.H., endorsed the CDC Advisory Committee on Immunization Practices’ (ACIP) recommendation for a booster shot of the Pfizer-BioNTech COVID-19 vaccine in certain populations and also recommended a booster dose for those in high risk occupational and institutional settings. The Food and Drug Administration’s (FDA) authorization and CDC’s guidance for use are important steps forward as we work to stay ahead of the virus and keep Americans safe.
In the crude analysis, the odds of a school-associated COVID-19 outbreak in schools with no mask requirement were 3.7 times higher than those in schools with an early mask requirement (odds ratio [OR] = 3.7; 95% CI = 2.2–6.5). After adjusting for potential described confounders, the odds of a school-associated COVID-19 outbreak in schools without a mask requirement were 3.5 times higher than those in schools with an early mask requirement (OR = 3.5; 95% CI = 1.8–6.9).
For the week ending September 17, 2021, HMM data were available for 73% of kindergarten through grade 12 public school students in 8,700 districts nationwide and varied by state (Supplementary Figure, https://stacks.cdc.gov/view/cdc/109969). Among these districts, 8,343 (96%) were offering full in-person learning, 322 (4%) were offering hybrid learning, and 35 (0.4%) were offering full remote learning. The largest number of districts with full remote learning (14) were in the West Census Region, followed by the South (11). Seven Midwest and two Northeast districts offered full remote learning. During August 2–September 17, 2021, systematic Internet searches identified announcements of 248 public districtwide closures and 384 individual school closures for ≥1 day attributable to COVID-19. Closures affected 1,801 schools (1.5% of all schools), 933,913 students, and 59,846 teachers in 44 states (Figure). The number of closures was highest in the South.
Counties without school mask requirements experienced larger increases in pediatric COVID-19 case rates after the start of school compared with counties that had school mask requirements (p<0.001) (Figure). The average change from week −1 (1–7 days before the start of school) to week 1 (7–13 days after the start of school) for counties with school mask requirements (16.32 cases per 100,000 children and adolescents aged <18 years per day) was 18.53 cases per 100,000 per day lower than the average change for counties without school mask requirements (34.85 per 100,000 per day) (p<0.001). Comparisons between pediatric COVID-19 case rates during the weeks before (weeks −3, −2, and −1) and after (weeks 0, 1, and 2) the start of school indicate that counties without school mask requirements experienced larger increases than those with school mask requirements (p<0.05). After controlling for covariates, school mask requirements remained associated with lower daily case rates of pediatric COVID-19 (β = −1.31; 95% confidence interval = −1.51 to −1.11) (p<0.001).
Vaccine hesitancy is waning, yet inequities in receipt remain. There is a clear public health opportunity to convert higher vaccine willingness into successfully delivered vaccinations.
Eligibility for Medicare at age 65 years, which has been associated with an immediate and substantial reduction in the uninsurance rate and improvements in measures of access to care, was not associated with mortality during the COVID-19 pandemic. These null findings may reflect the influence of state and federal policies that directed payments to hospitals for COVID-19 treatment and eliminated cost sharing for COVID-19 testing, both of which aimed to broaden access to COVID-19 testing and treatment.
September 23, 2021
In this study, the humoral response against SARS-CoV-2 at 1 month after vaccination was appropriate under treatment with cladribine and teriflunomide and diminished/absent under treatment with anti-CD20 therapies and S1P modulators. Delaying anti-CD20 infusions by 3 to 6 months before vaccination could, however, increase the probability of developing appropriate humoral responses, especially in selected clinically and radiologically stable patients. Limitations of the study include the short follow-up (only 1 month after vaccination), the relatively small sample size (especially of S1P modulators and cladribine groups), and the lack of data on additional DMTs. Future studies should aim at investigating antibody dynamics over time, if and how T cell–mediated responses after vaccination are influenced by DMTs, and whether these biological measures actually reflect vaccine efficacy in terms of preventing severe SARS-CoV-2 infection.
Ways That Mental Health Professionals Can Encourage COVID-19 Vaccination
Uptake of COVID-19 and other vaccines is low among younger adults, the age at onset for any mental health problems. Uptake is also lower in communities disproportionately affected by COVID-19. Creating opportunities for equitable access to COVID-19 vaccination has helped US efforts reach disproportionately affected communities to increase vaccine uptake. Engaging new approaches for increasing adult vaccination is a national priority. Although mental health is not the first thing that comes to mind when thinking about vaccination, strategic use of mental health professionals’ expertise could provide new opportunities to encourage COVID-19 vaccination. A better understanding of how mental health affects receipt of COVID-19 vaccines and better defining how mental health professionals can help, particularly for disproportionately affected communities, is fundamentally important now and could strengthen vaccination efforts. Engagement by mental health professionals’ organizations, and possibly trainings for their members, could be another important step.
September 22, 2021
Effectiveness of mRNA Covid-19 Vaccine among U.S. Health Care Personnel
The BNT162b2 and mRNA-1273 vaccines were highly effective under real-world conditions in preventing symptomatic Covid-19 in health care personnel, including those at risk for severe Covid-19 and those in racial and ethnic groups that have been disproportionately affected by the pandemic.
Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase
The mRNA-1273 vaccine continued to be efficacious in preventing Covid-19 illness and severe disease at more than 5 months, with an acceptable safety profile, and protection against asymptomatic infection was observed.
Clinical Characteristics of Multisystem Inflammatory Syndrome in Adults
These findings suggest that MIS-A is a serious hyperinflammatory condition that presents approximately 4 weeks after onset of acute COVID-19 with extrapulmonary multiorgan dysfunction.
September 17, 2021
Among U.S. adults without immunocompromising conditions, vaccine effectiveness against COVID-19 hospitalization during March 11–August 15, 2021, was higher for the Moderna vaccine (93%) than the Pfizer-BioNTech vaccine (88%) and the Janssen vaccine (71%). Although these real-world data suggest some variation in levels of protection by vaccine, all FDA-approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization.
Disaggregating race data can aid in identifying racial disparities among specific subpopulations and highlights the importance of partnering with communities to develop culturally responsive outreach teams and tailored public health interventions and vaccination campaigns to more effectively address health disparities.
In a random sample of recovered COVID-19 patients in Long Beach, California, one third of participants reported post-acute sequelae 2 months after their positive test result, with higher rates reported among persons aged ≥40 years, females, persons with preexisting conditions, and Black persons.
Among a cohort of 432,302 persons aged 2–19 years, the rate of body mass index (BMI) increase approximately doubled during the pandemic compared to a prepandemic period. Persons with prepandemic overweight or obesity and younger school-aged children experienced the largest increases.
This report has been corrected and republished. Below is the republished report. Please click here to view the detailed changes to the report.
During May 3–July 25, 2021, the overall age-adjusted vaccine effectiveness against hospitalization in New York was relatively stable 89.5%–95.1%). The overall age-adjusted vaccine effectiveness against infection for all New York adults declined from 91.8% to 75.0%.
September 16, 2021
Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting
Preapproval trials showed that messenger RNA (mRNA)–based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a good safety profile, yet these trials were subject to size and patient-mix limitations. An evaluation of the safety of the BNT162b2 mRNA vaccine with respect to a broad range of potential adverse events is needed.
Effectiveness of the Single-Dose Ad26.COV2.S COVID Vaccine
These non-randomized data across U.S. clinical practices show high and stable vaccine effectiveness of Ad26.COV2.S over time before the Delta variant emerged to when the Delta variant was dominant.
The Importance of Context in Covid-19 Vaccine Safety
Vaccine safety is critical for the successful implementation of any vaccination program, especially during a pandemic. In February 1976, the Centers for Disease Control and Prevention confirmed a cluster of cases of severe influenza-like illness among Army recruits at Fort Dix, New Jersey.
September 15, 2021
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine through 6 Months
BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine encoding a prefusion-stabilized, membrane-anchored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) full-length spike protein. BNT162b2 is highly efficacious against coronavirus disease 2019 (Covid-19) and is currently approved, conditionally approved, or authorized for emergency use worldwide. At the time of initial authorization, data beyond 2 months after vaccination were unavailable.
Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel
In this study involving participants who were 60 years of age or older and had received two doses of the BNT162b2 vaccine at least 5 months earlier, we found that the rates of confirmed Covid-19 and severe illness were substantially lower among those who received a booster (third) dose of the BNT162b2 vaccine.
Vaccine-Induced Thrombocytopenia with Severe Headache
Vaccine-induced immune thrombotic thrombocytopenia (VITT), a serious adverse event after vaccination with ChAdOx1 nCoV-19 (AstraZeneca) or Ad26.COV2.S (Johnson & Johnson–Janssen), is caused by platelet factor 4 (PF4)–dependent, platelet-activating antibodies. High-dose immune globulins and anticoagulation are the main treatments. In this report, we present evidence that vaccine-induced thrombocytopenia (VIT) without associated cerebral venous sinus thrombosis (CVST) or other thromboses and with severe headache as the heraldic symptom may precede VITT (“pre-VITT syndrome”).
SARS-CoV-2 Neutralization with BNT162b2 Vaccine Dose 3
We conducted a global, randomized, placebo-controlled, phase 1–2–3 pivotal trial in which two 30-μg doses of BNT162b2 (Pfizer–BioNTech) were administered 21 days apart (ClinicalTrials.gov number, NCT04368728. opens in new tab). These doses of vaccine had mainly low-grade side effects and provided 95% efficacy against coronavirus disease 2019 (Covid-19) from 7 days to approximately 2 months after dose 2. Efficacy waned to 84% between 4 and approximately 6 months after dose 2. Since vaccine authorization, viral variants have replaced the original strain, with the highly transmissible B.1.617.2 (delta) variant currently dominant. Although the effectiveness of the vaccine against severe disease, hospitalization, and death remains high, waning immunity and viral diversification create a possible need for a third vaccine dose.
The inactivated COVID-19 vaccine BBIBP-CorV is safe and well tolerated at all tested dose levels in participants aged 3–17 years. BBIBP-CorV also elicited robust humoral responses against SARS-CoV-2 infection after two doses. Our findings support the use of a 4 μg dose and two-shot regimen BBIBP-CorV in phase 3 trials in the population younger than 18 years to further ascertain its safety and protection efficacy against COVID-19.
September 14, 2021
Daily contact testing of school-based contacts was non-inferior to self-isolation for control of COVID-19 transmission, with similar rates of symptomatic infections among students and staff with both approaches. Infection rates in school-based contacts were low, with very few school contacts testing positive. Daily contact testing should be considered for implementation as a safe alternative to home isolation following school-based exposures.
September 13, 2021
Considerations in boosting COVID-19 vaccine immune responses
A new wave of COVID-19 cases caused by the highly transmissible delta variant is exacerbating the worldwide public health crisis, and has led to consideration of the potential need for, and optimal timing of, booster doses for vaccinated populations.1 Although the idea of further reducing the number of COVID-19 cases by enhancing immunity in vaccinated people is appealing, any decision to do so should be evidence-based and consider the benefits and risks for individuals and society.
September 10, 2021
HLA-B*15:01 is associated with asymptomatic SARS-CoV-2 infection
HLA-B*15:01 is strongly associated with asymptomatic infection with SARS-CoV-2 and is likely to be involved in the mechanism underlying early viral clearance.
Across 13 U.S. jurisdictions, incidence rate ratios for hospitalization and death changed relatively little after the SARS-CoV-2 B.1.617.2 (Delta) variant reached predominance, suggesting high, continued vaccine effectiveness against severe COVID-19. Case IRRs decreased, suggesting reduced vaccine effectiveness for prevention of SARS-CoV-2 infections.
Data on COVID-19 vaccine effectiveness (VE) since the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating strain in the United States are limited. CDC used the VISION Network* to examine medical encounters (32,867) from 187 hospitals and 221 emergency departments (EDs) and urgent care (UC) clinics across nine states during June–August 2021, beginning on the date the Delta variant accounted for >50% of sequenced isolates in each medical facility’s state. VISION Network methods have been published.
During February 1–August 6, 2021, vaccine effectiveness among U.S. veterans hospitalized at five Veterans Affairs Medical Centers was 87%. mRNA COVID-19 vaccines remain highly effective, including during periods of widespread circulation of the SARS-CoV-2 B.1.617.2 (Delta) variant. Vaccine effectiveness in preventing COVID-19–related hospitalization was 80% among adults aged ≥65 years compared with 95% among adults aged 18–64 years.
Long-Term Symptoms Among Adults Tested for SARS-CoV-2 — United States, January 2020–April 2021
In a nonprobability-based sample of U.S. adults tested for SARS-CoV-2, symptoms often associated with SARS-CoV-2 infection were common; 65.9% of respondents whose SARS-CoV-2 test results were positive reported symptoms lasting >4 weeks compared with 42.9% of those whose test results were negative. More persons who received positive test results (76.2%) reported persistence (>4 weeks) of at least one initially occurring symptom compared with those whose test results were negative (69.6%).
Using Wastewater Surveillance Data to Support the COVID-19 Response — United States, 2020–2021
Wastewater surveillance data have been used to deploy clinical testing resources, investigate possible irregularities in traditional surveillance, refine health messaging, and forecast clinical resource needs.
Compared with only masked exposure, close contacts with any unmasked exposure had higher adjusted odds of a positive test result. Each additional exposure was associated with a 40% increase in odds of a positive test.
Probenecid inhibits SARS-CoV-2 replication in vivo and in vitro
Effective vaccines are slowing the COVID-19 pandemic, but SARS-CoV-2 will likely remain an issue in the future making it important to have therapeutics to treat patients. There are few options for treating patients with COVID-19. We show probenecid potently blocks SARS-CoV-2 replication in mammalian cells and virus replication in a hamster model. Furthermore, we demonstrate that plasma concentrations up to 50-fold higher than the protein binding adjusted IC90 value are achievable for 24 h following a single oral dose. These data support the potential clinical utility of probenecid to control SARS-CoV-2 infection in humans.
September 9, 2021
Face masks for COVID pass their largest test yet
Face masks protect against COVID-19. That’s the conclusion of a gold-standard clinical trial in Bangladesh, which backs up the findings of hundreds of previous observational and laboratory studies.
The Spike (S) protein of SARS-CoV-2 binds ACE2 to direct fusion with host cells. S comprises a large external domain, a transmembrane domain, and a short cytoplasmic tail. Understanding the intracellular trafficking of S is relevant to SARS-CoV-2 infection, and to vaccines expressing full-length S from mRNA or adenovirus vectors. Here we report a proteomic screen for cellular factors that interact with the cytoplasmic tail of S. We confirm interactions with the COPI and COPII vesicle coats, ERM family actin regulators, and the WIPI3 autophagy component. The COPII binding site promotes exit from the endoplasmic reticulum, and although binding to COPI should retain S in the early Golgi where viral budding occurs, there is a suboptimal histidine residue in the recognition motif. As a result, S leaks to the surface where it accumulates and can direct the formation of multinucleate syncytia. Thus, the trafficking signals in the tail of S indicate that syncytia play a role in the SARS-CoV-2 lifecycle.
As the COVID-19 infection continues to ravage the world, the advent of an efficient as well as the economization of the existing RT-PCR based detection assay essentially can become a blessing in these testing times and significantly help in the management of the pandemic. This study demonstrated an innovative and rapid corroboration of COVID-19 test based on innovative multiplex PCR. An assessment of optimal PCR conditions to simultaneously amplify the SARS-CoV-2 genes E, S and RdRp has been made by fast-conventional and HRM coupled multiplex real-time PCR using the same sets of primers. All variables of practical value were studied by amplifying known target-sequences from ten-fold dilutions of archived positive samples of COVID-19 disease. The multiplexing with newly designed E, S and RdRp primers have shown an efficient amplification of the target region of SARS-CoV-2. A distinct amplification was observed in 37 min using thermal cycler while it took 96 min in HRM coupled real time detection using SYBR green over a wide range of template concentrations. Our findings revealed decent concordance with other commercially available detection kits. This fast HRM coupled multiplex real-time PCR with SYBR green approach offers rapid and sensitive detection of SARS-CoV-2 in a cost-effective manner apart from the added advantage of primer compatibility for use in conventional multiplex PCR. The highly reproducible novel approach can propel extended applicability for developing sustainable commercial product besides providing relief to a resource limited setting.
September 8, 2021
Effectiveness of Covid-19 Vaccines in Ambulatory and Inpatient Care Settings
There are limited data on the effectiveness of the vaccines against symptomatic coronavirus disease 2019 (Covid-19) currently authorized in the United States with respect to hospitalization, admission to an intensive care unit (ICU), or ambulatory care in an emergency department or urgent care clinic.
Covid-19 Vaccine Effectiveness and the Test-Negative Design
Observational studies are emerging as fundamental sources of information about vaccine effectiveness outside the controlled environment of randomized trials, and they are being used to generate evidence of effectiveness against outcomes that are underpowered in trials, such as hospitalization or intensive care unit (ICU) admission, or for narrow subgroups. These studies can monitor the waning of vaccine effectiveness or measure the performance of vaccines against novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants when large randomized, controlled trials are not feasible.
Decline in Pathogenic Antibodies over Time in VITT
Vaccine-induced immune thrombotic thrombocytopenia (VITT) has been described after vaccination with the adenoviral vector vaccines ChAdOx1 nCoV-19 (Oxford–AstraZeneca) and Ad26.COV2.S (Johnson & Johnson–Janssen). VITT is caused by platelet-activating anti–platelet factor 4 (PF4) IgG antibodies, the presence of which can be confirmed by anti–PF4–heparin IgG enzyme-linked immunosorbent assay (ELISA) in combination with PF4-enhanced washed-platelet–activation assays. Clinical and in vitro characteristics of acute VITT closely resemble (autoimmune) heparin-induced thrombocytopenia. A hallmark of heparin-induced thrombocytopenia is the transience of anti-PF4 antibodies. The persistence of pathogenic anti-PF4 antibodies in VITT is not well understood.
Effect of Vaccination on Transmission of SARS-CoV-2
Whether vaccination of individual persons for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protects members of their households is unclear. We investigated the effect of vaccination of health care workers in Scotland (who were among the earliest groups to be vaccinated worldwide) on the risk of coronavirus disease 2019 (Covid-19) among members of their households.
September 7, 2021
The rapid identification and isolation of infected individuals remains a key strategy for controlling the spread of SARS-CoV-2. Frequent testing of populations to detect infection early in asymptomatic or presymptomatic individuals can be a powerful tool for intercepting transmission, especially when the viral prevalence is low. However, RT-PCR testing—the gold standard of SARS-CoV-2 diagnosis—is expensive, making regular testing of every individual unfeasible. Sample pooling is one approach to lowering costs. By combining samples and testing them in groups the number of tests required is reduced, substantially lowering costs. Here we report on the implementation of pooling strategies using 3-d and 4-d hypercubes to test a professional sports team in South Africa. We have shown that infected samples can be reliably detected in groups of 27 and 81, with minimal loss of assay sensitivity for samples with individual Ct values of up to 32. We report on the automation of sample pooling, using a liquid-handling robot and an automated web interface to identify positive samples. We conclude that hypercube pooling allows for the reliable RT-PCR detection of SARS-CoV-2 infection, at significantly lower costs than lateral flow antigen (LFA) tests.
September 6, 2021
SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion
The SARS-CoV-2 B.1.617.2 (Delta) variant was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is 6-fold less sensitive to serum neutralising antibodies from recovered individuals, and 8-fold less sensitive to vaccine-elicited antibodies as compared to wild type (WT) Wuhan-1 bearing D614G. Serum neutralising titres against B.1.617.2 were lower in ChAdOx-1 versus BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies against the receptor binding domain (RBD) and N- terminal domain (NTD). B.1.617.2 demonstrated higher replication efficiency in both airway organoid and human airway epithelial systems compared to B.1.1.7, associated with B.1.617.2 spike in a predominantly cleaved state compared to B.1.1.7. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralising antibody as compared to WT spike. Additionally we observed that B.1.617.2 had higher replication and spike mediated entry as compared to B.1.617.1, potentially explaining B.1.617.2 dominance. In an analysis of over 130 SARS-CoV-2 infected healthcare workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx-1 vaccine effectiveness against B.1.617.2 relative to non- B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.
The efficacy of non-invasive ventilation (NIV) in acute respiratory failure secondary to SARS-CoV-2 infection remains controversial. Current literature mainly examined efficacy, safety and potential predictors of NIV failure provided out of the intensive care unit (ICU). On the contrary, the outcomes of ICU patients, intubated after NIV failure, remain to be explored. The aims of the present study are: (1) investigating in-hospital mortality in coronavirus disease 2019 (COVID-19) ICU patients receiving endotracheal intubation after NIV failure and (2) assessing whether the length of NIV application affects patient survival. This observational multicenter study included all consecutive COVID-19 adult patients, admitted into the twenty-five ICUs of the COVID-19 VENETO ICU network (February–April 2020), who underwent endotracheal intubation after NIV failure. Among the 704 patients admitted to ICU during the study period, 280 (40%) presented the inclusion criteria and were enrolled. The median age was 69 [60–76] years; 219 patients (78%) were male. In-hospital mortality was 43%. Only the length of NIV application before ICU admission (OR 2.03 (95% CI 1.06–4.98), p = 0.03) and age (OR 1.18 (95% CI 1.04–1.33), p < 0.01) were identified as independent risk factors of in-hospital mortality; whilst the length of NIV after ICU admission did not affect patient outcome. In-hospital mortality of ICU patients intubated after NIV failure was 43%. Days on NIV before ICU admission and age were assessed to be potential risk factors of greater in-hospital mortality.
September 3, 2021
After spring break 2021, COVID-19 cases increased rapidly at a Chicago university despite mitigation measures. Interviews indicated that the majority of cases occurred in unvaccinated persons with a history of recent travel. Sequencing corroborated multiple introductions to campus and demonstrated that even a single importation can result in many cases.
In 2020, adolescent coverage with Tdap and the first dose of MenACWY remained high and continued to improve for HPV vaccines, with some disparities. Adolescents living outside a metropolitan statistical area (MSA) had lower vaccination coverage compared with adolescents living in MSA principal cities.
Targeted screening identified 48 cases of COVID-19 during September–November 2020, 18 (38%) of which were in asymptomatic persons. This population of infected students was demographically different from those identified through other testing programs, more risk-tolerant, and less willing to participate in public health prevention activities.
COVID-19 cases, emergency department visits, and hospital admissions increased from June to August 2021 among persons aged 0-17 years. Emergency department visits and hospital admissions in a 2-week period in August 2021 were higher in states with lower population vaccination coverage and lower in states with higher vaccination coverage.
Weekly COVID-19–associated hospitalization rates among children and adolescents rose nearly five-fold during late June–mid-August 2021, coinciding with increased circulation of the highly transmissible SARS-CoV-2 Delta variant. The proportions of hospitalized children and adolescents with severe disease were similar before and during the period of Delta predominance. Hospitalization rates were 10 times higher among unvaccinated than among fully vaccinated adolescents.
Development of ACE2 autoantibodies after SARS-CoV-2 infection
Many patients with a history of SARS-CoV-2 infection have antibodies specific for ACE2. Patients with ACE2 antibodies have lower activity of soluble ACE2 in plasma. Plasma from these patients also inhibits exogenous ACE2 activity. These findings are consistent with the hypothesis that ACE2 antibodies develop after SARS-CoV-2 infection and decrease ACE2 activity. This could lead to an increase in the abundance of Ang II, which causes a proinflammatory state that triggers symptoms of PASC.
September 2, 2021
Effectiveness of an Inactivated SARS-CoV-2 Vaccine in Chile
Our results suggest that the inactivated SARS-CoV-2 vaccine effectively prevented Covid-19, including severe disease and death, a finding that is consistent with results of phase 2 trials of the vaccine. (Funded by Agencia Nacional de Investigación y Desarrollo and others.)
Covid-Induced Changes in Health Care Delivery — Can They Last?
COVID-19 shook the U.S. health care system. The immediate-term fallout was predictable: in-person utilization plummeted and many adults deferred routine care. Health care professionals, hospitals, and patients had to — and did — adapt rapidly to this unprecedented crisis, quickly flexing to increase the use of delivery modes such as telemedicine and home-based care.
September 1, 2021
Resurgence of SARS-CoV-2 Infection in a Highly Vaccinated Health System Workforce
In December 2020, the University of California San Diego Health (UCSDH) workforce experienced a dramatic increase in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Vaccination with mRNA vaccines began in mid-December 2020; by March, 76% of the workforce had been fully vaccinated, and by July, the percentage had risen to 87%. Infections had decreased dramatically by early February 2021.
Public Health Law after Covid-19
COVID-19 has spurred an outbreak of a different kind: litigation. To combat the pandemic, officials imposed extensive community-level mitigation measures using their broad but largely untested emergency powers. In response, more than 1000 suits challenged orders shuttering businesses, banning indoor worship services, restricting travel, and mandating mask wearing.1 As with other social aspects of the pandemic, this litigation will have lasting effects.
August 31, 2021
Neither COVID-19 vaccination nor COVID-19 testing was required before either event. Among 122 primary cases, 104 (85%) were in persons who were not fully vaccinated, and 18 (15%) were in fully vaccinated persons. Eight of 38 (21%) close contacts of the 18 fully vaccinated persons subsequently became infected with SARS-CoV-2. No vaccinated persons with COVID-19 were hospitalized.
During March 2020–January 2021, patients with COVID-19 had nearly 16 times the risk for myocarditis compared with patients who did not have COVID-19, and risk varied by sex and age.
In conclusion, through the use of an isothermal, reverse transcription-free (RTF) amplification method, RTF-EXPAR, involving a DNA-selective restriction endonuclease, we have demonstrated the successful detection of SARS-CoV-2 RNA in a total assay time of less than 10 min. In comparison to existing molecular tests, RTF-EXPAR holds a number of advantages.
August 27, 2021
During May 23–June 12, 2021, 26 laboratory-confirmed COVID-19 cases occurred among Marin County, California, elementary school students and their contacts following exposure to an unvaccinated infected teacher. The attack rate in one affected classroom was 50%; risk correlated with seating proximity to the teacher.
As of July 31, 2021, coverage with ≥1 dose of COVID-19 vaccine among adolescents aged 12–17 years was 42%, and 32% had completed the series. Series completion rates varied widely by state, ranging from 11% to 60%, and was 25% for adolescents aged 12–13 years, 30% for those aged 14–15 years, and 40% for those aged 16–17 years.
During September 1, 2020–March 31, 2021, a total of 463 school-associated cases were reported among students attending public TK–12 schools in person and 3,927 among staff members working on-site. During the same period, 105,577 cases among children and adolescents aged 5–17 years and 771,409 cases among adults aged 18–79 years were reported in LAC. School-associated case rates remained low among students, ranging from 110 per 100,000 in September to 859 in December 2020 (Figure). Case rates among all children and adolescents aged 5–17 years in the county were higher during most of the period, ranging from 167 per 100,000 in September to 2,938 in December 2020. School-associated case rates among staff members were lowest in September 2020 (125 per 100,000), peaked in December 2020 (4,109), and fell sharply through March 2021 (188).
August 24, 2021
During December 14, 2020–April 10, 2021, data from the HEROES-RECOVER Cohorts,* a network of prospective cohorts among frontline workers, showed that the Pfizer-BioNTech and Moderna mRNA COVID-19 vaccines were approximately 90% effective in preventing symptomatic and asymptomatic infection with SARS-CoV-2, the virus that causes COVID-19, in real-world conditions. This report updates vaccine effectiveness (VE) estimates including all COVID-19 vaccines available through August 14, 2021, and examines whether VE differs for adults with increasing time since completion of all recommended vaccine doses. VE before and during SARS-CoV-2 B.1.617. (Delta) variant predominance, which coincided with an increase in reported COVID-19 vaccine breakthrough infections, were compared.
During May 1–July 25, 2021, among 43,127 SARS-CoV-2 infections in residents of Los Angeles County, California, 10,895 (25.3%) were in fully vaccinated persons, 1,431 (3.3%) were in partially vaccinated persons, and 30,801 (71.4%) were in unvaccinated persons. On July 25, infection and hospitalization rates among unvaccinated persons were 4.9 and 29.2 times, respectively, those in fully vaccinated persons. In July, when the Delta variant was predominant, cycle threshold values were similar for unvaccinated, partially vaccinated, and vaccinated persons.
August 20, 2021
Rapid point-of-care antigen testing shortens the turn-around time and might be a valuable tool in reducing transmission of SARS-CoV-2 in rural communities by facilitating rapid isolation and quarantine.
Disparities in Excess Mortality Associated with COVID-19 — United States, 2020
These findings could help guide targeted public health messaging and mitigation efforts to reduce disparities in COVID-19–associated mortality in the United States, by identifying the racial/ethnic and age groups with the highest excess mortality rates.
August 19, 2021
Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK
The effectiveness of BNT162b2, ChAdOx1, and mRNA-1273 vaccines against new SARS-CoV-2 infections requires continuous re-evaluation, given the increasingly dominant Delta variant. We investigated theeffectiveness of the vaccines in a large community-based survey of randomly selected households across the UK. We found that the effectiveness of BNT162b2 and ChAd0x1 against any infections (new PCR positives) and infections with symptoms or high viral burden is reduced with the Delta variant. A single dose of the mRNA-1273 vaccine had similar or greater effectiveness compared to a single dose of BNT162b2 or ChAdOx1. Effectiveness of two doses remains at least as great as protection afforded by prior natural infection. The dynamics of immunity following second doses differed significantly between BNT162b2 and ChAdOx1, with greater initial effectiveness against new PCR-positives but faster declines in protection against high viral burden and symptomatic infection with BNT162b2. There was no evidence that effectiveness varied by dosing interval, but protection was higher among those vaccinated following a prior infection and younger adults. With Delta, infections occurring following two vaccinations had similar peak viral burden to those in unvaccinated individuals. SARS-CoV-2 vaccination still reduces new infections, but effectiveness and attenuation of peak viral burden are reduced with Delta.
The Covid-19 Infodemic — Applying the Epidemiologic Model to Counter Misinformation
hroughout the world, including the United States, medical professionals and patients are facing both a pandemic and an infodemic — the first caused by SARS-CoV-2 and the second by misinformation and disinformation. The Annenberg Public Policy Center’s tracking of social and legacy media has found that millions of people have been exposed to deceptive material alleging that SARS-CoV-2 is a hoax or that experts are exaggerating its severity and the extent of its spread, that masks are ineffective or increase infection risk, or that Covid-19 vaccines cause the disease, alter the recipient’s DNA, or include tracking devices. Believing such claims is associated with a lower likelihood of engaging in preventive behavior and a lower willingness to be vaccinated.
August 18, 2021
Joint Statement from HHS Public Health and Medical Experts on COVID-19 Booster Shots
Today, public health and medical experts from the U.S. Department of Health and Human Services (HHS) released the following statement on the Administration’s plan for COVID-19 booster shots for the American people.
These findings support the implementation of multicomponent approach to controlling the pandemic, centered on vaccination, as well as other prevention strategies such as masking and physical distancing.
mRNA vaccine effectiveness against COVID-19–associated hospitalizations was sustained over 24 weeks; ongoing monitoring is needed as new SARS-CoV-2 variants emerge. To reduce hospitalization, all eligible persons should be offered COVID-19 vaccination.
Multicomponent COVID-19 prevention strategies, including vaccination of nursing home staff members, residents, and visitors, are critical. An additional dose of COVID-19 vaccine might be considered for nursing home and long-term care facility residents to optimize a protective immune response.
Early Convalescent Plasma for High-Risk Outpatients with Covid-19
The administration of Covid-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of Covid-19 did not prevent disease progression.
Pan-Sarbecovirus Neutralizing Antibodies in BNT162b2-Immunized SARS-CoV-1 Survivors
Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern pose a challenge to the effectiveness of current vaccines. A vaccine that could prevent infection caused by known and future variants of concern as well as infection with pre-emergent sarbecoviruses (i.e., those with potential to cause disease in humans in the future) would be ideal. Here we provide data showing that potent cross-clade pan-sarbecovirus neutralizing antibodies are induced in survivors of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) infection who have been immunized with the BNT162b2 messenger RNA (mRNA) vaccine. The antibodies are high-level and broad-spectrum, capable of neutralizing not only known variants of concern but also sarbecoviruses that have been identified in bats and pangolins and that have the potential to cause human infection. These findings show the feasibility of a pan-sarbecovirus vaccine strategy.
Breakthrough Infections in BNT162b2-Vaccinated Health Care Workers
Vaccinated health care workers can be infected with variants of concern transmitted from unvaccinated household contacts and may transmit SARS-CoV-2 in the hospital if not screened early enough. Finally, variants of concern may not only be more transmissible than the original SARS-CoV-2 but may also escape vaccine protection more frequently.
Myocarditis after Covid-19 mRNA Vaccination
In these two adult cases of histologically confirmed, fulminant myocarditis that had developed within 2 weeks after Covid-19 vaccination, a direct causal relationship cannot be definitively established because we did not perform testing for viral genomes or autoantibodies in the tissue specimens. However, no other causes were identified by PCR assay or serologic examination.
August 17, 2021
This large prospective cohort study found that COVID-19 vaccines were well-tolerated among individuals who were pregnant, lactating, or planning pregnancy. A strength of this study was the ability to compare vaccine reactions and perceptions in pregnant and lactating individuals vs individuals of similar age and fertility intentions who were neither pregnant nor lactating. Vaccination reactions for day 1 were similar among groups and comparable with findings among pregnant individuals previously reported.6 All groups reported increased reactions following dose 2 of BNT162b2 and mRNA-1273 vaccines.
A vaccine-induced public antibody protects against SARS-CoV-2 and emerging variants
Of five monoclonal antibodies that potently neutralized the WA1/2020 D614G strain, all retained neutralizing capacity against the B.1.617.2 variant, four also neutralized the B.1.1.7 variant, and only one, 2C08, also neutralized the B.1.351 and B.1.1.28 variants. 2C08 reduced lung viral load and morbidity in hamsters challenged with the WA1/2020 D614G, B.1.351, or B.1.617.2 strains. Clonal analysis identified 2C08-like public clonotypes among B cells responding to SARS-CoV-2 infection or vaccination in 41 out of 181 individuals. Thus, 2C08-like antibodies can be induced by SARS-CoV-2 vaccines and mitigate resistance by circulating variants of concern.
Intranasal vaccination induces the nasal IgA antibody which is protective against respiratory viruses, such as influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, understanding how mucosal immune responses are elicited following viral infection is important for developing better vaccines. Here, we focused on the role of nasal commensal bacteria in the induction of immune responses following influenza virus infection. To deplete nasal bacteria, we intranasally administered antibiotics to mice before influenza virus infection and found that antibiotic-induced disruption of nasal bacteria could release bacterial components which stimulate the virus-specific antibody responses. Since commensal bacteria in nasal mucosa were significantly lower than those in the oral cavity, intranasal administration of split virus vaccine alone was insufficient to induce the vaccine-specific antibody response. However, intranasal supplementation of cultured oral bacteria from a healthy human volunteer enhanced antibody responses to the intranasally administered vaccine. Therefore, both integrity and amounts of nasal bacteria may be critical for an effective intranasal vaccine.
SARS-CoV-2 delta variant neutralisation after heterologous ChAdOx1-S/BNT162b2 vaccination
Safety considerations associated with the Oxford–AstraZeneca COVID-19 ChAdOx1-S vaccine (AZD1222) have led many public health agencies to recommend a heterologous boost with an mRNA vaccine after prime vaccination with ChAdOx1-S instead of a homologous boost. The first results of a phase 2 trial from Spain and additional reports from observational studies suggest robust immune responses accompanied by acceptable reactogenicity after ChAdOx1-S prime and BNT162b2.
ChAdOx1 nCoV-19 was well tolerated, showing favourable safety and immunogenicity in people with HIV, including heightened immunogenicity in SARS-CoV-2 baseline-seropositive participants. People with HIV showed cross-reactive binding antibodies to the beta variant and Asp614Gly wild-type, and high responders retained neutralisation against beta.
People with psychiatric disorders, especially severe mental illness, have increased morbidity and mortality from COVID-19 infection; therefore, vaccination against COVID-19 should be prioritised for this vulnerable group, which has been done in several countries (eg, Denmark, Germany, The Netherlands, and the UK).
August 16, 2021
Association of Age and Pediatric Household Transmission of SARS-CoV-2 Infection
Younger children may have greater risk of transmitting SARS-CoV-2 to caregivers and siblings in the household than older children.
Regardless of symptoms, the vast majority of participants (953 of 954, greater than 99.9%) developed spike IgG antibodies 14 or more days following dose 2; 1 participant who was taking immunosuppressant medication did not develop IgG antibodies (Figure). Reporting clinically significant symptoms, age younger than 60 years, female sex, receipt of Moderna vaccine, and prior SARS-CoV-2 exposure were independently associated with higher median IgG measurements, after adjusting for time after dose 2.
Our findings suggest an overall increased risk of Bell's palsy after CoronaVac vaccination. However, the beneficial and protective effects of the inactivated COVID-19 vaccine far outweigh the risk of this generally self-limiting adverse event. Additional studies are needed in other regions to confirm our findings.
Perceiving a Pandemic: Global–Local Incompatibility and COVID-19 Superspreading Events
Supporting our theory, we find that localized county-level infection rates of COVID-19 are unreliable predictors of national infection rates. However, they explain a significant proportion of variance in judgments of national infection rates, contributing to judgment errors. These results support our theoretical approach for modeling this unique judgment context as an incompatibility between global and local information, providing a framework to predict how citizens will react to novel large-scale (global) risks. Our results also help explain the extreme polarization witnessed in the U.S. regarding perceptions of the risks of the COVID-19 pandemic. Accounting for the variability of local experiences with a pandemic can help future generations prepare for how to respond to similar threats more effectively.
August 15, 2021
Immune Correlates Analysis of the mRNA-1273 COVID-19 Vaccine Efficacy Trial
Binding and neutralizing antibodies correlated with COVID-19 risk and vaccine efficacy and likely have utility in predicting mRNA-1273 vaccine efficacy against COVID-19.
August 13, 2021
In a large-scale SARS-CoV-2 surveillance programme in Madurai, India, we identified equal risk of asymptomatic infection among children, teenagers, and working-age adults, and increasing risk of infection and death associated with older age and comorbidities. Establishing whether surveillance practices or differences in infection severity account for gaps between observed and expected mortality is of crucial importance to establishing the burden of COVID-19 in India.
Rapid genome sequencing in hospitals to identify potential vaccine-escape SARS-CoV-2 variants
SARS-CoV-2 genome sequencing is embedded in academic and public health laboratories, but whether there are benefits to rapid sequencing in front-line hospital laboratories is unclear. We did rapid genome sequencing of SARS-CoV-2-positive nose and throat swabs from patients admitted to our hospital since July 7, 2021, to identify potential SARS-CoV-2 vaccine-escape variants for infection control and public health purposes.
Change in Saliva RT-PCR Sensitivity Over the Course of SARS-CoV-2 Infection
Saliva was sensitive for detecting SARS-CoV-2 in symptomatic individuals during initial weeks of infection, but sensitivity in asymptomatic SARS-CoV-2 carriers was less than 60% at all time points. As COVID-19 testing strategies in workplaces, schools, and other shared spaces are optimized, low saliva sensitivity in asymptomatic infections must be considered.5 This study suggests saliva-based RT-PCR should not be used for asymptomatic COVID-19 screening.
In this study of a diverse group of midcareer medical school faculty, the experience of working during the pandemic appeared to have had important positive impacts on physician investigators and PhD scientists, contributing to their vitality and professional dedication that were associated with intrinsic motivators.
New section on considerations for use of an additional dose of COVID-19 vaccine following a primary vaccine series
New section on considerations for use of an additional mRNA COVID-19 vaccine dose after an initial 2-dose primary mRNA COVID-19 vaccine series for immunocompromised people
These findings suggest that the COVID-19 pandemic affected insurance coverage and the ability of low-income people to access health care, but it appears that the presence of Medicaid expansion was protective for Black and Latinx individuals.
CRISPR-inspired systems have been extensively developed for applications in genome editing and nucleic acid detection. Here, we introduce a CRISPR-based peptide display technology to facilitate customized, high-throughput in vitro protein interaction studies. We show that bespoke peptide libraries fused to catalytically inactive Cas9 (dCas9) and barcoded with unique single guide RNA (sgRNA) molecules self-assemble from a single mixed pool to programmable positions on a DNA microarray surface for rapid, multiplexed binding assays. We develop dCas9-displayed saturation mutagenesis libraries to characterize antibody-epitope binding for a commercial anti-FLAG monoclonal antibody and human serum antibodies. We also show that our platform can be used for viral epitope mapping and exhibits promise as a multiplexed diagnostics tool. Our CRISPR-based peptide display platform and the principles of complex library self-assembly using dCas9 could be adapted for rapid interrogation of varied customized protein libraries or biological materials assembly using DNA scaffolding.
August 12, 2021
Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant
Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations.
Heterologous ChAdOx1-nCoV19–BNT162b2 vaccination provides superior immunogenicity against COVID-19
At the height of the COVID-19 vaccination campaign, supply and local availability issues for the approved vaccines—together with worries about rare side-effects (thrombotic thrombocytopenia)—necessitated the switch to heterologous vaccination schedules, commonly known as mixing vaccines. Several studies have now been completed addressing the efficacy and safety of this practice during the battle for immunisation against SARS-CoV-2 and its variants.
SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses on healthy SARS-CoV-2 naïve and recovered individuals prior to and following mRNA prime and boost vaccination. Vaccination induced rapid antigen-specific CD4+ T cell responses in naïve subjects after the first dose, whereas CD8+ T cell responses developed gradually and were variable in magnitude. Vaccine-induced Th1 and Tfh cell responses following the first dose correlated with post-boost CD8+ T cell and neutralizing antibody, respectively. Integrated analysis revealed coordinated immune responses with distinct trajectories in SARS-CoV-2 naïve and recovered individuals. Lastly, whereas booster vaccination improved T cell responses in SARS-CoV-2 naïve subjects, the second dose had little effect in SARS-CoV-2 recovered individuals. These findings highlight the role of rapidly primed CD4+ T cells in coordinating responses to the second vaccine dose in SARS-CoV-2 naïve individuals.
Confronting Our Next National Health Disaster — Long-Haul Covid
Now that more than half of U.S. adults have been vaccinated against SARS-CoV-2, masking and distancing mandates have been relaxed, and Covid-19 cases and deaths are on the decline, there is a palpable sense that life can return to normal. Though most Americans may be able to do so, restoration of normality does not apply to the 10% to 30% of those who are still experiencing debilitating symptoms months after being infected with Covid-19.
The COVID States Project #60: COVID-19 vaccine misinformation: From uncertainty to resistance
In mid-July 2021, President Biden emphatically claimed that social media platforms were “killing people” by facilitating the spread of vaccine misinformation. Not long after, Senate Republican leader Mitch McConnell similarly declared that misinformation was to be blamed for the low vaccination rates of Americans. The public debate that followed brought to the forefront a series of important questions. How prevalent is the public’s belief in vaccine misinformation? Is that belief associated with vaccine resistance? Are some social groups more susceptible to it than others? Are social media companies responsible for the higher levels of vaccine resistance among some of their users?
This report focuses on the first three questions, exploring misinformation beliefs across social groups and their connection with vaccine attitudes. We address the last question in our previous report and in a post published by the Washington Post’s Monkey Cage blog.
Hospital-acquired SARS-CoV-2 infection in the UK's first COVID-19 pandemic wave
Prevention of hospital-acquired infections is a critical aspect of clinical management of COVID-19 as hospital-acquired infections have been a common feature of previous novel coronavirus outbreaks.1 The number of COVID-19 patients in UK hospitals reached high levels during the first pandemic wave of 2020, and higher levels still in the subsequent winter wave. We assessed the magnitude of nosocomial COVID-19 in acute and long-term National Health Service (NHS) hospital facilities in the UK during the first pandmic wave.
The heterologous ChAdOx1 nCov-19–BNT162b2 immunisation with 10–12-week interval, recommended in Germany, is well tolerated and improves immunogenicity compared with homologous ChAdOx1 nCov-19 vaccination with 10–12-week interval and BNT162b2 vaccination with 3-week interval. Heterologous prime-boost immunisation strategies for COVID-19 might be generally applicable.
COVID-19 vaccine equity and booster doses
The debate on COVID-19 vaccine equity has been long-running, and we have previously weighed in on the topic. However, the facts that (1) by Aug 9, only 12·6 million of the 4·46 billion doses administered globally were in low-income countries, (2) 3·65 billion have been administered in high-income (HICs) and upper-middle-income countries, and (3) WHO Director-General Tedros Adhanom Ghebreyesus actually had to issue a plea for a moratorium on third-dose boosters in HICs on Aug 4, mean that we, again, need to add our voice to the demand for equitable access to vaccines.
August 11, 2021
Evaluation of mRNA-1273 SARS-CoV-2 Vaccine in Adolescents
The mRNA-1273 vaccine had an acceptable safety profile in adolescents. The immune response was similar to that in young adults, and the vaccine was efficacious in preventing Covid-19.
Clinical Features of Vaccine-Induced Immune Thrombocytopenia and Thrombosis
The high mortality associated with VITT was highest among patients with a low platelet count and intracranial hemorrhage. Treatment remains uncertain, but identification of prognostic markers may help guide effective management.
Randomized Trial of a Third Dose of mRNA-1273 Vaccine in Transplant Recipients
In organ-transplant recipients, the standard two-dose vaccination strategy for coronavirus disease 2019 (Covid-19) has suboptimal immunogenicity.1 Both patients and health care providers have questioned whether a third-dose booster in transplant recipients would be safe and enhance immune response.
This cohort study examines 869 079 adult women, including 18 715 women with COVID-19, who underwent childbirth at 499 US medical centers between March 1, 2020, and February 28, 2021. Women with COVID-19 had increased mortality, need for intubation and ventilation, and intensive care unit admission. These findings suggest that COVID-19 was associated with increased risk of morbidity and mortality for women giving birth.
Our results suggest that breast milk from women vaccinated with the novel mRNA-based Pfizer-BioNTech vaccine contains specific anti–SARS-CoV-2 IgG(S1) antibodies. Furthermore, we found that after the second dose, breast milk IgG(S1) levels increased and were positively associated with corresponding serum levels.
Single doses of either BNT162b2 or ChAdOx1 nCoV-19 in older people induces humoral immunity in most participants, and is markedly enhanced by previous infection. Cellular responses were weaker, but showed enhancement after the ChAdOx1 nCoV-19 vaccine at the 5–6 week timepoint.
Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis
Molnupiravir is an orally available antiviral drug candidate currently in phase III trials for the treatment of patients with COVID-19. Molnupiravir increases the frequency of viral RNA mutations and impairs SARS-CoV-2 replication in animal models and in humans. Here, we establish the molecular mechanisms underlying molnupiravir-induced RNA mutagenesis by the viral RNA-dependent RNA polymerase (RdRp). Biochemical assays show that the RdRp uses the active form of molnupiravir, β-d-N4-hydroxycytidine (NHC) triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate. When the RdRp uses the resulting RNA as a template, NHC directs incorporation of either G or A, leading to mutated RNA products. Structural analysis of RdRp–RNA complexes that contain mutagenesis products shows that NHC can form stable base pairs with either G or A in the RdRp active center, explaining how the polymerase escapes proofreading and synthesizes mutated RNA. This two-step mutagenesis mechanism probably applies to various viral polymerases and can explain the broad-spectrum antiviral activity of molnupiravir.
August 10, 2021
Persistent Endotheliopathy in the Pathogenesis of Long COVID Syndrome
Collectively, our findings demonstrate that sustained endotheliopathy is common in convalescent COVID-19 and raise the intriguing possibility that this may contribute to Long COVID pathogenesis.
August 10, 2021
On July 22, 2021, the Advisory Committee on Immunization Practices reviewed updated benefit-risk analyses after Janssen and mRNA COVID-19 vaccination and concluded that the benefits outweigh the risks for rare serious adverse events after COVID-19 vaccination.
Emphasize personal health benefits to boost COVID-19 vaccination rates
Based on a nationally quota representative sample of 3,048 adults in the United States, our findings suggest that several forms of public messages can increase vaccine intentions, but messaging that emphasizes personal health benefits had the largest impact.
Inhaled budesonide improves time to recovery, with a chance of also reducing hospital admissions or deaths (although our results did not meet the superiority threshold), in people with COVID-19 in the community who are at higher risk of complications.
Gradual relaxation of PHSMs should be carefully planned during the roll-out of vaccination programmes, and easing of travel restrictions weighed against risk of reintroducing outbreaks, to avoid overwhelming health systems and minimise deaths related to COVID-19.
August 9, 2021
In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). Our observational study highlights that while both mRNA COVID-19 vaccines strongly protect against infection and severe disease, further evaluation of mechanisms underlying differences in their effectiveness such as dosing regimens and vaccine composition are warranted.
Ethnic minorities exhibit higher multimorbidity despite younger age structures and disproportionate exposure to unscored risk factors including obesity and deprivation. Household overcrowding, air pollution, housing quality and adult skills deprivation are associated with multilobar pneumonia on presentation and ICU admission which are mortality risk factors. Risk tools need to reflect risks predominantly affecting ethnic minorities.
Sensitive extraction-free SARS-CoV-2 RNA virus detection using a chelating resin
Current conventional detection of SARS-CoV-2 involves collection of a patient sample with a nasopharyngeal swab, storage of the swab during transport in a viral transport medium, extraction of RNA, and quantitative reverse transcription PCR (RT-qPCR). We developed a simplified preparation method using a chelating resin, Chelex, that obviates RNA extraction during viral testing. Direct detection RT-qPCR and digital-droplet PCR was compared to the current conventional method with RNA extraction for simulated samples and patient specimens. The heat-treatment in the presence of Chelex markedly improved detection sensitivity as compared to heat alone, and lack of RNA extraction shortens the overall diagnostic workflow. Furthermore, the initial sample heating step inactivates SARS-CoV-2 infectivity, thus improving workflow safety. This fast RNA preparation and detection method is versatile for a variety of samples, safe for testing personnel, and suitable for standard clinical collection and testing on high throughput platforms.
August 6, 2021
Broad betacoronavirus neutralization by a stem helix–specific human antibody
The spillovers of betacoronaviruses in humans and the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants highlight the need for broad coronavirus countermeasures. We describe five monoclonal antibodies (mAbs) cross-reacting with the stem helix of multiple betacoronavirus spike glycoproteins isolated from COVID-19 convalescent individuals. Using structural and functional studies, we show that the mAb with the greatest breadth (S2P6) neutralizes pseudotyped viruses from three different subgenera through the inhibition of membrane fusion, and we delineate the molecular basis for its cross-reactivity. S2P6 reduces viral burden in hamsters challenged with SARS-CoV-2 through viral neutralization and Fc-mediated effector functions. Stem helix antibodies are rare, oftentimes of narrow specificity, and can acquire neutralization breadth through somatic mutations. These data provide a framework for structure-guided design of pan-betacoronavirus vaccines eliciting broad protection.
Reduced Risk of Reinfection with SARS-CoV-2 After COVID-19 Vaccination — Kentucky, May–June 2021
Among Kentucky residents infected with SARS-CoV-2 in 2020, vaccination status of those reinfected during May–June 2021 was compared with that of residents who were not reinfected. In this case-control study, being unvaccinated was associated with 2.34 times the odds of reinfection compared with being fully vaccinated. To reduce their likelihood for future infection, all eligible persons should be offered COVID-19 vaccine, even those with previous SARS-CoV-2 infection.
Among adults aged 65–74 years, effectiveness of full vaccination for preventing hospitalization was 96% for Pfizer-BioNTech, 96% for Moderna, and 84% for Janssen COVID-19 vaccines; among adults aged ≥75 years, effectiveness of full vaccination for preventing hospitalization was 91% for Pfizer-BioNTech, 96% for Moderna, and 85% for Janssen COVID-19 vaccines. Efforts to increase vaccination coverage are critical to reducing the risk for COVID-19–related hospitalization, particularly in older adults.
During April–June 2021, COVID-19 cases caused by the Delta variant increased rapidly in Mesa County, Colorado. Compared with that in other Colorado counties, incidence, intensive care unit admissions, COVID-19 case fatality ratios, and the proportion of cases in fully vaccinated persons were significantly higher in Mesa County. Crude vaccine effectiveness against symptomatic infection was estimated to be 78% for Mesa County and 89% for other Colorado counties. Vaccination is critical for preventing infection, serious illness, and death associated with SARS-CoV-2 infection (including the Delta variant). Multicomponent prevention strategies, such as masking in indoor settings irrespective of vaccination status as well as optimal surveillance testing and infection prevention and control, should be considered in areas of high incidence.
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has caused a significant number of fatalities and worldwide disruption. To identify drugs to repurpose to treat SARS-CoV-2 infections, we established a screen to measure the dimerization of angiotensin-converting enzyme 2 (ACE2), the primary receptor for the virus. This screen identified fenofibric acid, the active metabolite of fenofibrate. Fenofibric acid also destabilized the receptor-binding domain (RBD) of the viral spike protein and inhibited RBD binding to ACE2 in enzyme-linked immunosorbent assay (ELISA) and whole cell-binding assays. Fenofibrate and fenofibric acid were tested by two independent laboratories measuring infection of cultured Vero cells using two different SARS-CoV-2 isolates. In both settings at drug concentrations, which are clinically achievable, fenofibrate and fenofibric acid reduced viral infection by up to 70%. Together with its extensive history of clinical use and its relatively good safety profile, this study identifies fenofibrate as a potential therapeutic agent requiring an urgent clinical evaluation to treat SARS-CoV-2 infection.
August 5, 2021
Contact Tracing for Covid-19 — A Digital Inoculation against Future Pandemics
Outbreaks of coronavirus disease 2019 (Covid-19) emerged in the United States and in European countries in February 2020. Urgent action was called for, since experts estimated that 30 to 70% of people in these Western countries could become infected — a frightening projection at a time when the Covid-19 mortality rate was estimated to be substantially higher than we now know it to be.
SARS-CoV-2 Variants in Patients with Immunosuppression
Patients with immunosuppression are at risk for prolonged infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In several case reports, investigators have indicated that multimutational SARS-CoV-2 variants can arise during the course of such persistent cases of coronavirus disease 2019 (Covid-19).
August 4, 2021
Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19
Subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. Among the participants who became infected, REGEN-COV reduced the duration of symptomatic disease and the duration of a high viral load.
Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19
In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis.
Surviving Covid-19 with Heparin?
Patients who are admitted to the hospital with coronavirus disease 2019 (Covid-19) are at high risk for thrombosis, particularly venous thromboembolism (VTE). In a meta-analysis of 66 studies, the overall prevalence of VTE among patients with Covid-19 was 14.1%, with the highest incidence (22.7%) among those admitted to intensive care units (ICUs).
Myocarditis and Pericarditis After Vaccination for COVID-19
Some vaccines are associated with myocarditis, including mRNA vaccines, and the Centers for Disease Control and Prevention recently reported a possible association between COVID-19 mRNA vaccines and myocarditis, primarily in younger male individuals within a few days after the second vaccination, at an incidence of about 4.8 cases per 1 million. This study shows a similar pattern, although at higher incidence, suggesting vaccine adverse event underreporting. Additionally, pericarditis may be more common than myocarditis among older patients.
Conflicting evidence surrounding SARS-CoV-2 transmission, particularly airborne transmission, may have contributed to heterogeneous recommendations for respiratory protection across countries and organizations.1 Variability among guidelines may generate confusion, anxiety, and mistrust among health care professionals (HCPs) regarding the ability of respiratory protection to prevent SARS-CoV-2 transmission. We assessed variation in international and national guidelines on respiratory protection for HCPs in hospital settings during the first year of the COVID-19 pandemic.
Is oropharyngeal sampling a reliable test to detect SARS-CoV-2?
The authors concluded that, compared with a nasopharyngeal swab, a pooled nasal and oropharyngeal swab offered the best alternative sampling approach to diagnose SARS-CoV-2 infection, followed by saliva and nasal swabs. Oropharyngeal swabs were not recommended for diagnosis because of low sensitivity and positive predictive value.
Post-acute sequelae of COVID-19 in a non-hospitalized cohort: Results from the Arizona CoVHORT
There were 303 non-hospitalized individuals with a positive lab-confirmed COVID-19 test who were followed for a median of 61 days (range 30–250). COVID-19 positive participants were mostly female (70%), non-Hispanic white (68%), and on average 44 years old. Prevalence of PASC at 30 days post-infection was 68.7% (95% confidence interval: 63.4, 73.9). The most common symptoms were fatigue (37.5%), shortness-of-breath (37.5%), brain fog (30.8%), and stress/anxiety (30.8%). The median number of symptoms was 3 (range 1–20). Amongst 157 participants with longer follow-up (≥60 days), PASC prevalence was 77.1%.
Mucormycosis after COVID-19 in a patient with diabetes
A 44-year-old man attended our hospital reporting reduced vision in his left eye. 10 days earlier he had been started on treatment with supplemental oxygen, intravenous antibiotics, and corticosteroids because of a moderately severe pneumonia caused by SARS-CoV-2. The patient explained that a blackish patch—extending from just below his left eye to the left side of his face to the level of his mouth—had also developed 2 days earlier.
Although most countries and healthcare systems worldwide have been affected by the COVID-19 pandemic, some groups of the population may be more vulnerable to detrimental effects of the pandemic on mental health than others. The aim of this systematic review was to synthesise evidence currently available from systematic reviews on the impact of COVID-19 and other coronavirus outbreaks on mental health for groups of the population thought to be at increased risk of detrimental mental health impacts.
August 3, 2021
Estimating SARS-CoV-2 infections from deaths, confirmed cases, tests, and random surveys
The novel coronavirus SARS-CoV-2 has infected over 33 million people in the United States. Nationwide, over 600,000 have died in the COVID-19 pandemic, which has necessitated shutdowns of schools and sectors of the economy. The extent of the virus’ spread remains uncertain due to biases in test data. We combine multiple data sources to estimate the true number of infections in all US states. These data include representative random testing surveys from Indiana and Ohio, which provide potentially unbiased prevalence estimates. We find that approximately 60% of infections have gone unreported. Even so, only about 20% of the United States had been infected as of early March 2021, suggesting that the country was far from herd immunity at that point.
New Federal Guidance Says COVID-19’s Long-term Effects Can Qualify as a Disability
People in the US who experience persistent, recurring, or new symptoms after infection with COVID-19—a condition known as long COVID—can qualify as having a disability under federal civil rights laws and receive appropriate accommodations and services, the Biden-Harris administration announced last week.
Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2
Although COVID-19 in children is usually of short duration with low symptom burden, some children with COVID-19 experience prolonged illness duration. Reassuringly, symptom burden in these children did not increase with time, and most recovered by day 56. Some children who tested negative for SARS-CoV-2 also had persistent and burdensome illness. A holistic approach for all children with persistent illness during the pandemic is appropriate.
Endomembrane targeting of human OAS1 p46 augments antiviral activity
Many host RNA sensors are positioned in the cytosol to detect viral RNA during infection. However, most positive-strand RNA viruses replicate within a modified organelle co-opted from intracellular membranes of the endomembrane system, which shields viral products from cellular innate immune sensors. Targeting innate RNA sensors to the endomembrane system may enhance their ability to sense RNA generated by viruses that use these compartments for replication. Here, we reveal that an isoform of oligoadenylate synthetase 1, OAS1 p46, is prenylated and targeted to the endomembrane system. Membrane localization of OAS1 p46 confers enhanced access to viral replication sites and results in increased antiviral activity against a subset of RNA viruses including flaviviruses, picornaviruses, and SARS-CoV-2. Finally, our human genetic analysis shows that the OAS1 splice-site SNP responsible for production of the OAS1 p46 isoform correlates with protection from severe COVID-19. This study highlights the importance of endomembrane targeting for the antiviral specificity of OAS1 and suggests that early control of SARS-CoV-2 replication through OAS1 p46 is an important determinant of COVID-19 severity.
August 2, 2021
Unless new drinking habits are formed during the pandemic, decreases in alcohol use among college students are unlikely to be sustained as social distancing measures are removed. Colleges may want to target interventions to students who have responded to stress with increased alcohol use, partly by addressing difficulties with distance learning.
Setting Priorities to Address Research Gaps in Long-term COVID-19 Outcomes in Children
Increasing numbers of people with prolonged symptoms after recovery from COVID-19 infection (long COVID) have been reported, prompting calls for research. Symptoms of long COVID are poorly characterized, with several phenotypes described, and the causes, treatments, and outcomes are unknown. Calls for research fail to address long COVID in children and adolescents. Given the demand for appropriate care for patients with this condition, agencies have published guidelines on treatment. However, these guidelines inappropriately combine research requirements and services for the children and older adults.
Flawed ivermectin preprint highlights challenges of COVID drug studies
Throughout the pandemic, the anti-parasite drug ivermectin has attracted much attention, particularly in Latin America, as a potential way to treat COVID-19. But scientists say that recent, shocking revelations of widespread flaws in the data of a preprint study reporting that the medication greatly reduces COVID-19 deaths dampens ivermectin’s promise — and highlights the challenges of investigating drug efficacy during a pandemic.
Ivermectin (Still) Lacks Scientific Support as a COVID-19 Drug
The available scientific evidence does not support the use of ivermectin, an antiparastic drug, for the treatment or prevention of COVID-19 outside the context of clinical trials, according to a new report from Cochrane, an international organization that reviews medical research and provides guidance about clinical practice.
July 30, 2021
In a large population-based study, COVID-19 diagnosis increased the risk of VPTB, PTB, and early term birth, particularly among people with medical comorbidities. Considering increased circulation of COVID-19 variants, preventative measures, including vaccination, should be prioritized for birthing persons.
Jurisdictions might consider expanded prevention strategies, including universal masking in indoor public settings, particularly for large public gatherings that include travelers from many areas with differing levels of SARS-CoV-2 transmission.
Statement from CDC Director Rochelle P. Walensky, MD, MPH on Today’s MMWR
Today, some of those data were published in CDC’s Morbidity and Mortality Weekly Report (MMWR), demonstrating that Delta infection resulted in similarly high SARS-CoV-2 viral loads in vaccinated and unvaccinated people. High viral loads suggest an increased risk of transmission and raised concern that, unlike with other variants, vaccinated people infected with Delta can transmit the virus. This finding is concerning and was a pivotal discovery leading to CDC’s updated mask recommendation. The masking recommendation was updated to ensure the vaccinated public would not unknowingly transmit virus to others, including their unvaccinated or immunocompromised loved ones.
Mild local and systemic reactions are common among adolescents following Pfizer-BioNTech vaccine, and serious adverse events are rare. The Advisory Committee on Immunization Practices conducted a risk-benefit assessment and continues to recommend the Pfizer-BioNTech COVID-19 vaccine for all persons aged ≥12 years.
During March 2021, 300 LTCFs reported COVID-19 vaccination coverage for their HCP. COVID-19 vaccination coverage was highest among physicians (75.1%) and lowest among aides (45.6%). Vaccination coverage among aides was lower in facilities located in zip code areas with higher levels of social vulnerability.
Weekly SARS-CoV-2 antigen screening tests required of all employees returning for in-school instruction in the School District of Philadelphia found a 95% lower percentage of positive test results among persons who reported receipt of 2 doses of COVID-19 mRNA vaccine (0.09%) than among those who were unvaccinated (1.77%).
CoronaVac, an inactivated SARS-CoV-2 vaccine, has been approved for emergency use in several countries. However, its immunogenicity in immunocompromised individuals has not been well established. We initiated a prospective phase 4 controlled trial (no. NCT04754698, CoronavRheum) in 910 adults with autoimmune rheumatic diseases (ARD) and 182 age- and sex-frequency-matched healthy adults (control group, CG), who received two doses of CoronaVac. The primary outcomes were reduction of ≥15% in both anti-SARS-CoV-2 IgG seroconversion (SC) and neutralizing antibody (NAb) positivity 6 weeks (day 69 (D69)) after the second dose in the ARD group compared with that in the CG. Secondary outcomes were IgG SC and NAb positivity at D28, IgG titers and neutralizing activity at D28 and D69 and vaccine safety. Prespecified endpoints were met, with lower anti-SARS-Cov-2 IgG SC (70.4 versus 95.5%, P < 0.001) and NAb positivity (56.3 versus 79.3%, P < 0.001) at D69 in the ARD group than in the CG. Moreover, IgG titers (12.1 versus 29.7, P < 0.001) and median neutralization activity (58.7 versus 64.5%, P = 0.013) were also lower at D69 in patients with ARD. At D28, patients with ARD presented with lower IgG frequency (18.7 versus 34.6%, P < 0.001) and NAb positivity (20.6 versus 36.3%, P < 0.001) than that of the CG. There were no moderate/severe adverse events. These data support the use of CoronaVac in patients with ARD, suggesting reduced but acceptable short-term immunogenicity. The trial is still ongoing to evaluate the long-term effectiveness/immunogenicity.
July 29, 2021
Tofacitinib in Patients Hospitalized with Covid-19 Pneumonia
Among patients hospitalized with Covid-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than placebo.
BNT162b2-Elicited Neutralization against New SARS-CoV-2 Spike Variants
Because these data show that the newly emerged B.1.526, B.1.429, and B.1.1.7+E484K variants remain susceptible to an important vaccine-elicited immune effector (neutralizing antibody), they confirm the importance of mass immunization with current, highly effective, authorized vaccines as a central strategy to end the Covid-19 pandemic.
July 28, 2021
Covid-19 Breakthrough Infections in Vaccinated Health Care Workers
Among fully vaccinated health care workers, the occurrence of breakthrough infections with SARS-CoV-2 was correlated with neutralizing antibody titers during the peri-infection period. Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur.
In this cohort study of 801 hospital health care workers (HCWs), the risk of getting infected with SARS-CoV-2 was nearly 4-fold higher among HCWs on COVID-19 wards compared with HCWs not in patient care. Combined phylogenetic and epidemiological analyses found no patient-to-HCW transmission but several occurrences of HCW-to-HCW transmission.
Association Between Mood Disorders and Risk of COVID-19 Infection, Hospitalization, and Death
In this systematic review and meta-analysis of more than 91 million people, individuals with preexisting mood disorders, compared with those without mood disorders, had significantly higher pooled odds ratios for COVID-19 hospitalization and death. There were no associations between preexisting mood disorders and risk of COVID-19 infection or severe events.
During the 3-day study period, an individual email nudge caused more than twice as many HCWs to register for a COVID-19 vaccination compared with HCWs in the control condition, with no significant difference between the 2 emails. A limitation of this trial is that due to the imminent closure of employee-only vaccination clinics, we could only delay the intervention in the control group by 3 days. Moreover, by choosing to compare 2 behaviorally informed emails, we are unable to exclude the possibility that a plain reminder might have had the same effect. Furthermore, we could not measure actual vaccination, as appointment slots were unexpectedly unavailable for many who registered for one.
Aberrant glycosylation of anti-SARS-CoV-2 IgG is a pro-thrombotic stimulus for platelets
Aberrant glycosylation of anti-SARS-CoV-2 IgG immune complexes increases platelet thrombus formation on vWF
Inhibition of syk, btk, P2Y12 or FcγRIIA reverses enhancement of thrombus formation mediated by anti-SARS-CoV-2 immune complexes
SARS-CoV-2 Lambda variant exhibits higher infectivity and immune resistance
SARS-CoV-2 Lambda, a new variant of interest, is now spreading in some South American countries; however, its virological features and evolutionary trait remain unknown. Here we reveal that the spike protein of the Lambda variant is more infectious and it is attributed to the T76I and L452Q mutations. The RSYLTPGD246-253N mutation, a unique 7-amino-acid deletion mutation in the N-terminal domain of the Lambda spike protein, is responsible for evasion from neutralizing antibodies.
Reproducible Breath Metabolite Changes in Children with SARS-CoV-2 Infection
SARS-CoV-2 infection is diagnosed through detection of specific viral nucleic acid or antigens from respiratory samples. These techniques are relatively expensive, slow, and susceptible to false-negative results. A rapid noninvasive method to detect infection would be highly advantageous. Compelling evidence from canine biosensors and studies of adults with COVID-19 suggests that infection reproducibly alters human volatile organic compound (VOC) profiles. To determine whether pediatric infection is associated with VOC changes, we enrolled SARS-CoV-2 infected and uninfected children admitted to a major pediatric academic medical center. Breath samples were collected from children and analyzed through state-of-the-art GCxGC-ToFMS. Isolated features included 84 targeted VOCs. Candidate biomarkers that were correlated with infection status were subsequently validated in a second, independent cohort of children. We thus find that six volatile organic compounds are significantly and reproducibly increased in the breath of SARS-CoV-2 infected children. Three aldehydes (octanal, nonanal, and heptanal) drew special attention, as aldehydes are also elevated in the breath of adults with COVID-19. Together, these biomarkers demonstrate high accuracy for distinguishing pediatric SARS-CoV-2 infection and support the ongoing development of novel breath-based diagnostics.
Ivermectin for preventing and treating COVID‐19
Based on the current very low‐ to low‐certainty evidence, we are uncertain about the efficacy and safety of ivermectin used to treat or prevent COVID‐19. The completed studies are small and few are considered high quality. Several studies are underway that may produce clearer answers in review updates. Overall, the reliable evidence available does not support the use of ivermectin for treatment or prevention of COVID‐19 outside of well‐designed randomized trials.
July 27, 2021
Given the spread of the highly transmissible Delta variant, local decision-makers should assess the following factors to inform the need for layered prevention strategies across a range of settings: level of SARS-CoV-2 community transmission, health system capacity, vaccination coverage, capacity for early detection of increases in COVID-19 cases, and populations at risk for severe outcomes from COVID-19.
Lower serum 25(OH)D levels associated with higher risk of COVID-19 infection in U.S. Black women
The present results suggest that U.S. Black women with lower levels of 25(OH)D are at increased risk of infection with COVID-19. Further work is needed to confirm these findings and determine the optimal level of 25(OH)D for a beneficial effect.
In this systematic review and meta-analysis of 16 observational studies in 7 countries with 19 086 patients, mental health disorders were associated with increased COVID-19 mortality according to both pooled crude and adjusted odds ratios. Patients with severe mental health disorders had the highest odds ratios.
July 26, 2021
Corneal confocal microscopy identifies corneal small nerve fibre loss and increased DCs in patients with long COVID, especially those with neurological symptoms. CCM could be used to objectively identify patients with long COVID.
A ‘mix and match’ approach to SARS-CoV-2 vaccination
Heterologous dosing with the adenovirus-based ChAdOx1 (AstraZeneca) vaccine followed by an mRNA vaccine induced stronger immune responses than did the homologous ChAdOx1 vaccine series, according to recent immunogenicity studies.
Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination
Recipients of both the homologous vector regimen and the heterologous vector/mRNA combination reported greater reactogenicity following the priming vector vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA boosting. Taken together, heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles.
Because the Janssen vaccine received emergency use authorization, the US Centers for Disease Control and Prevention recommended that individuals with an immediate and potentially allergic reaction to the first dose of the Pfizer-BioNTech or Moderna mRNA COVID-19 vaccine could receive a Janssen single dose subsequently. However, our data suggest that most patients with immediate and potentially allergic reactions to mRNA COVID-19 vaccines tolerate a second dose. Therefore, it may not be necessary to consider this, to our knowledge, largely unstudied alternative mixed series approach. Although earlier work provided a shared framework for the clinical approach, our pooled study was limited by its retrospective study design, referral bias, and lack of a shared evaluation protocol among participating institutions.
Corneal confocal microscopy identifies corneal small nerve fibre loss and increased DCs in patients with long COVID, especially those with neurological symptoms. CCM could be used to objectively identify patients with long COVID.
July 24, 2021
Tocilizumab in COVID-19 therapy: who benefits, and how?
There is clinical evidence to suggest tocilizumab therapy in patients with COVID-19 may be associated with thrombotic events. To better analyse the efficacy and safety of tocilizumab, the RECOVERY Collaborative Group should specify the number of thrombotic or thromboembolic events observed in their study and specifically detail the proportion of patients receiving therapeutic anticoagulation in both groups. These results will better inform clinical practice on the use of tocilizumab for patients with COVID-19.
Tocilizumab in COVID-19 therapy: who benefits, and how?
In conclusion, clinical trials of IL-6 antagonist therapy, such as RECOVERY and sarilumab COVID-19 global studies, should consider reanalysis of their results as a function of IL-6 baseline concentrations. More generally, clinical trials of personalised precision medicine, based on cytokine profiling, are needed for optimisation of COVID-19 therapy.
Tocilizumab in COVID-19 therapy: who benefits, and how? – Authors' reply
These data do not, therefore, support the hypothesis of restricting treatment with tocilizumab to those patients with the highest levels of CRP or other biomarkers of inflammation. On the contrary, these data raise the question of whether even more COVID-19 patients could benefit from IL-6 inhibition if a lower threshold (CRP <75 mg/L) were used to initiate treatment.
July 23, 2021
Memory B Cell Repertoire for Recognition of Evolving SARS-CoV-2 Spike
Although emerging SARS-CoV-2 variants of concern escaped binding by many members of the groups associated with the most potent neutralizing activity, some antibodies in each of those groups retained affinity—suggesting that otherwise redundant components of a primary immune response are important for durable protection from evolving pathogens. Our results furnish a global atlas of S-specific memory B cell repertoires and illustrate properties driving viral escape and conferring robustness against emerging variants.
Strategies for disseminating guidance to dentists during the COVID-19 pandemic
This presentation summarizes and evaluates the clinical guidance and other evidence-based resources developed for dentists and patients by the American Dental Association (ADA) during the COVID-19 pandemic.
Weekly SARS-CoV-2 antigen screening tests required of all employees returning for in-school instruction in the School District of Philadelphia found a 95% lower percentage of positive test results among persons who reported receipt of 2 doses of COVID-19 mRNA vaccine (0.09%) than among those who were unvaccinated (1.77%).
The highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects the respiratory tract and is transmitted, in part, by respiratory droplets and aerosols. Consequently, unvaccinated people are encouraged to wear masks in public, self-quarantine if symptomatic, and practice social distancing. Despite these precautions, millions are dying. As the pandemic takes its toll, vaccines are once again headline news, notably for the speed of their development and the success of messenger RNA (mRNA) vaccines. Given the respiratory tropism of the virus, however, it seems surprising that only seven of the nearly 100 SARS-CoV-2 vaccines currently in clinical trials are delivered intranasally. Advantages of intranasal vaccines include needle-free administration, delivery of antigen to the site of infection, and the elicitation of mucosal immunity in the respiratory tract.
Influenza viruses and human metapneumovirus circulated at historic lows through May 2021. In April 2021, respiratory syncytial virus activity increased. Common human coronaviruses, parainfluenza viruses, and respiratory adenoviruses have been increasing since January or February 2021. Rhinoviruses and enteroviruses began to increase in June 2020.
Coronavirus Disease 2019 as a Possible Cause of Severe Orbital Cellulitis
Infection by severe respiratory syndrome coronavirus 2 (coronavirus disease 2019) has been the most important public health event of the last 100 years. The number of cases and deaths caused by this disease, its potential to rapidly spread and the search for a vaccine have been the center of discussion all over the world for over 1 year. In addition to the number of cases and all social, economic, and public health consequences of the pandemic, the variety of symptoms and clinical signs presented by infected patients has been subject of several studies and case reports.
July 22, 2021
Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19
SARS-CoV-2 infection can cause severe respiratory COVID-19. However, many individuals present with isolated upper respiratory symptoms, suggesting potential to constrain viral pathology to the nasopharynx. Which cells SARS-CoV-2 primarily targets and how infection influences the respiratory epithelium remains incompletely understood. We performed scRNA-seq on nasopharyngeal swabs from 58 healthy and COVID-19 participants. During COVID-19, we observe expansion of secretory, loss of ciliated, and epithelial cell repopulation via deuterosomal expansion. In mild/moderate COVID-19, epithelial cells express anti-viral/interferon-responsive genes, while cells in severe COVID-19 have muted anti-viral responses despite equivalent viral loads. SARS-CoV-2 RNA+ host-target cells are highly heterogenous, including developing ciliated, interferon-responsive ciliated, AZGP1high goblet, and KRT13+ “hillock”-like cells, and we identify genes associated with susceptibility, resistance, or infection response. Our study defines protective and detrimental responses to SARS-CoV-2, the direct viral targets of infection, and suggests that failed nasal epithelial anti-viral immunity may underlie and precede severe COVID-19.
This study identified several work environment factors that have significantly affected health care workers' well-being and resilience during the COVID-19 pandemic. This knowledge has practical relevance for health care leaders who aim to better understand and address the well-being and resilience of the health care workforce during this pandemic and beyond.
Spatiotemporal invasion dynamics of SARS-CoV-2 lineage B.1.1.7 emergence
We identify a multi-stage spatial invasion process in which early B.1.1.7 growth rates were associated with mobility and asymmetric lineage export from a dominant source location, enhancing the effects of B.1.1.7’s increased intrinsic transmissibility. We further explore how B.1.1.7 spread was shaped by non-pharmaceutical interventions and spatial variation in previous attack rates. Our findings show that careful accounting of the behavioral and epidemiological context within which variants of concern emerge is necessary to interpret correctly their observed relative growth rates.
Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines
Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infection when administered in real-world conditions, and the vaccines attenuated the viral RNA load, risk of febrile symptoms, and duration of illness among those who had breakthrough infection despite vaccination. (Funded by the National Center for Immunization and Respiratory Diseases and the Centers for Disease Control and Prevention.)
July 21, 2021
Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant
Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant (30.7%; 95% confidence interval [CI], 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant.
Vaccine Effectiveness Studies in the Field
The original trials of vaccines against infection with severe acute respiratory disease coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), have clearly shown vaccine efficacy. However, questions crucial to vaccination policy remain, at best, only partially answered. These include the effect of new virus variants, the timing between vaccine doses, the effect of vaccines on asymptomatic infection in contrast to severe disease, the waning of vaccine immunity, and the potentially enhanced effectiveness of mix-and-match strategies that might be used with booster shots.
Household Transmission of SARS-CoV-2 from Children and Adolescents
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is often asymptomatic or results in only mild disease. Data on the extent of transmission of SARS-CoV-2 from children and adolescents in the household setting, including transmission to older persons who are at increased risk for severe disease, are limited. After an outbreak of coronavirus disease 2019 (Covid-19) at an overnight camp, we conducted a retrospective cohort study involving camp attendees and their household contacts to assess secondary transmission and factors associated with household transmission.
SARS-CoV-2 Human Challenge Studies — Establishing the Model during an Evolving Pandemic
Human challenge studies (also called controlled human infection models), in which researchers intentionally administer an infectious agent to volunteers, have played major roles in vaccine and treatment development and in elucidation of pathogenesis and immunity. Such studies are not normally undertaken during a pandemic, however, and the potential risks and benefits of such research with SARS-CoV-2 in this setting have triggered widespread debate. While other commentators have made theoretical arguments for and against SARS-CoV-2 challenge studies, a consortium of academics, industry collaborators, and the British government (through the Human Challenge Programme of the U.K. Vaccines Taskforce) has now proceeded to address the technical and ethical considerations to enable such studies. The consortium’s practical application of ethical principles against a backdrop of rapidly emerging evidence carries lessons for future outbreaks.
July 20, 2021
More Genetic Clues to COVID-19 Susceptibility and Severity
Many factors influence our risk of illness from SARS-CoV-2, the coronavirus responsible for COVID-19. That includes being careful to limit our possible exposures to the virus, as well as whether we have acquired immunity from a vaccine or an earlier infection. But once a person is infected, a host of other biological factors, including age and pre-existing medical conditions, will influence one’s risk of becoming severely ill.
July 19, 2021
Abelacimab for Prevention of Venous Thromboembolism
This trial showed that factor XI is important for the development of postoperative venous thromboembolism. Factor XI inhibition with a single intravenous dose of abelacimab after total knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding.
Inhibitors of VPS34 and fatty-acid metabolism suppress SARS-CoV-2 replication
Mechanistic studies with compounds targeting multiple steps up- and downstream of fatty acid synthase (FASN) identify the importance of triacylglycerol production and protein palmitoylation as requirements for efficient viral RNA synthesis and infectious virus production. Further, FASN knockout results in significantly impaired SARS-CoV-2 replication that can be rescued with fatty acid supplementation. Together, these studies clarify roles for VPS34 and fatty acid metabolism in SARS-CoV-2 replication and identify promising avenues for the development of countermeasures against SARS-CoV-2.
July 16, 2021
Among persons vaccinated during March 29–April 6, 2021, compared with December 14, 2020–January 3, 2021, in North Carolina, the proportion who were Black nearly doubled, and the share of vaccine doses administered to Hispanic persons doubled during this period, approaching the proportion of the state population for these groups aged ≥16 years.
July 15, 2021
Pre-existing mental disorders, in particular psychotic and mood disorders, and exposure to antipsychotics and anxiolytics were associated with COVID-19 mortality in both crude and adjusted models. Although further research is required to determine the underlying mechanisms, our findings highlight the need for targeted approaches to manage and prevent COVID-19 in at-risk patient groups identified in this study.
July 14, 2021
Covid-19: Regional policies and local infection risk: Evidence from Italy with a modelling study
Even within the same region, Italy’s provinces differ in exposure to covid-19 infection risk due to local characteristics. Regional policies did not eliminate these differences, but may have dampened them. Our evidence can be relevant for policy-makers who need to design non-pharmaceutical interventions. It also provides a methodological suggestion for researchers who attempt to estimate their causal effects.
July 13, 2021
Antibody response after second BNT162b2 dose in allogeneic HSCT recipients
In this first evaluation of immunogenicity in allogeneic HSCT recipients after two vaccine doses, we observed overall frequent and high levels of humoral responses, which contrasts with recent observations in solid organ transplant recipients who are receiving very long-term pharmacological immunosuppression.4 We identified lymphocyte count as well as recent pharmacological immunosuppression, rather than the sole timing of vaccination after HSCT, as determinants of humoral response. Our findings support the large scale vaccination of allogeneic HSCT recipients, although additional multicentre and long-term studies are needed to specify the level of immunological protection against infection, also taking into account the effect of a third vaccine dose in non-responding patients.
mRNA Vaccines May Pack More Persistent Punch Against COVID-19 Than Thought
Many people, including me, have experienced a sense of gratitude and relief after receiving the new COVID-19 mRNA vaccines. But all of us are also wondering how long the vaccines will remain protective against SARS-CoV-2, the coronavirus responsible for COVID-19.
July 9, 2021
Disrupted Resolution Mechanisms Favor Altered Phagocyte Responses in Covid-19
The present findings suggest that downregulation of systemic SPM concentrations is linked with both increased disease severity and dysregulated phagocyte function. They also identify the upregulation of these mediators by dexamethasone as a potential mechanism in host protective activities elicited by this drug in COVID-19 patients. Taken together, our findings elucidate a role for altered resolution mechanisms in the disruption of phagocyte responses and the propagation of systemic inflammation in COVID-19.
July 8, 2021
The quest to find genes that drive severe COVID
Since last March, research teams around the world have scoured the genomes of more than 100,000 people with COVID-19, hoping to find genetic clues to who will be hit hardest by an infection with the virus SARS-CoV-2. What’s emerged from this effort is a dozen or so genetic variants that have a strong statistical association with a person’s chances of developing COVID-19 and becoming gravely ill with the disease, the teams report in a summary analysis published on 8 July in Nature.
Mapping the human genetic architecture of COVID-19
The identification of novel host genetic factors associated with COVID-19, with unprecedented speed, was made possible by the community of human genetic researchers coming together to prioritize sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization
Variant Delta was resistant to neutralization by some anti-NTD and anti-RBD mAbs including Bamlanivimab, which were impaired in binding to the Spike. Sera from convalescent patients collected up to 12 months post symptoms were 4 fold less potent against variant Delta, relative to variant Alpha (B.1.1.7). Sera from individuals having received one dose of Pfizer or AstraZeneca vaccines barely inhibited variant Delta. Administration of two doses generated a neutralizing response in 95% of individuals, with titers 3 to 5 fold lower against Delta than Alpha. Thus, variant Delta spread is associated with an escape to antibodies targeting non-RBD and RBD Spike epitopes.
July 7, 2021
Effectiveness of an Inactivated SARS-CoV-2 Vaccine in Chile
Our results suggest that the inactivated SARS-CoV-2 vaccine effectively prevented Covid-19, including severe disease and death, a finding that is consistent with results of phase 2 trials of the vaccine.
Therapeutic Plasma Exchange in Vaccine-Induced Immune Thrombotic Thrombocytopenia
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is characterized by thrombosis and thrombocytopenia that occurs 5 to 30 days after ChAdOx1 nCoV-19 vaccination and is associated with heparin-independent platelet factor 4 (PF4) antibodies.
Infection and Vaccine-Induced Neutralizing-Antibody Responses to the SARS-CoV-2 B.1.617 Variants
A second wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in India is leading to the emergence of SARS-CoV-2 variants. The B.1.617.1 (or kappa) and B.1.617.2 (or delta) variants were first identified in India and have rapidly spread to several countries throughout the world. These variants contain mutations within the spike protein located in antigenic sites recognized by antibodies with potent neutralizing activity.
Because of the risk of a sudden worsening of patients conditions and myocarditis association with considerable mortality and morbidity, a knowledge of this cardiac complication of Covid-19 disease is crucial for healthcare professionals.
Drugs repurposed for COVID-19 by virtual screening of 6,218 drugs and cell-based assay
To tackle the challenges, we report advanced virtual screening with pre- and postdocking pharmacophore filtering of 6,218 drugs for COVID-19. Notably, 7 out of 38 compounds showed efficacies in inhibiting SARS-CoV-2 in Vero cells. Three of these were also found to inhibit SARS-CoV-2 in human Calu-3 cells. Furthermore, three drug combinations showed strong synergistic effects in SARS-CoV-2 inhibition at their clinically achievable concentrations.
Deaths and Hospitalizations Averted by Rapid U.S. Vaccination Rollout
The COVID-19 pandemic has unleashed devastating health and economic crises worldwide, causing more than 3.9 million deaths and 183 million reported infections globally.
Antibody epitopes in vaccine-induced immune thrombotic thrombocytopenia
Our data indicates VITT antibodies can mimic the effect of heparin by binding to a similar site on PF4, allowing PF4 tetramers to cluster and form immune complexes, which in turn cause FcγRIIa-dependent platelet activation. These results provide an explanation for VITT antibody-induced platelet activation that could contribute to thrombosis.
We show herein that the SARS-CoV-2 Nsp3 protein also contains a SUD domain that interacts with G4s. Indeed, interactions between SUD proteins and both DNA and RNA G4s were evidenced by G4 pull-down, Surface Plasmon Resonance and Homogenous Time Resolved Fluorescence. These interactions can be disrupted by mutations that prevent oligonucleotides from folding into G4 structures and, interestingly, by molecules known as specific ligands of these G4s. Structural models for these interactions are proposed and reveal significant differences with the crystallographic and modeled 3D structures of the SARS-CoV SUD-NM/G4 interaction. Altogether, our results pave the way for further studies on the role of SUD/G4 interactions during SARS-CoV-2 replication and the use of inhibitors of these interactions as potential antiviral compounds.
July 6, 2021
On June 23, 2021, the Advisory Committee on Immunization Practices concluded that the benefits of COVID-19 vaccination to individual persons and at the population level clearly outweighed the risks of myocarditis after vaccination.
SARS-CoV-2 neutralizing antibodies: Longevity, breadth, and evasion by emerging viral variants
A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization, was associated with COVID-19 severity. A subgroup of “high responders” maintained high neutralizing responses over time, representing ideal convalescent plasma donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants and VOC. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal responders and vaccine monitoring and design.
July 5, 2021
Nationwide, firearm purchasing and firearm violence increased substantially during the first months of the coronavirus pandemic. At the state level, the magnitude of the increase in purchasing was not associated with the magnitude of the increase in firearm violence. Increases in purchasing may have contributed to additional firearm injuries from domestic violence in April and May. Results suggest much of the rise in firearm violence during our study period was attributable to other factors, indicating a need for additional research.
July 2, 2021
A simulated infected meeting participant who was exhaling aerosols was placed in a room with two simulated uninfected participants and a simulated uninfected speaker. Using two HEPA air cleaners close to the aerosol source reduced the aerosol exposure of the uninfected participants and speaker by up to 65%. A combination of HEPA air cleaners and universal masking reduced exposure by up to 90%.
July 1, 2021
The 1 case attributed to a COVID-19 patient encounter occurred within an at-risk period and involved an AGP. We observed a very low risk for COVID-19 infection attributable to patient encounters among EMS first responders, supporting clinical strategies that maintain established practices for treating patients in emergency conditions.
June 29, 2021
Although access to in-person, hybrid, and virtual learning modes varied throughout the school year, during January–April 2021, access to full-time in-person learning for non-Hispanic White students increased by 36.6 percentage points, 31.1 percentage points for non-Hispanic Black students, 22.0 percentage points for Hispanic students, and 26.6 percentage points for students of other race/ethnicities.
June 25, 2021
Among 26,174 surveyed state, tribal, local, and territorial public health workers, 53.0% reported symptoms of at least one mental health condition in the past 2 weeks. Symptoms were more prevalent among those who were unable to take time off or worked ≥41 hours per week.
June 24, 2021
New Metric Identifies Coronavirus Hotspots in Real Time
During the pandemic, it’s been critical to track in real time where the coronavirus is spreading at home and abroad. But it’s often hard for public health officials to know whether changes in the reported number of COVID-19 cases over time truly reflect the spread of the virus or whether they are confounded by changes in testing levels or lags in the reporting of results.
In summary, we show that the Delta VOC in Scotland was found mainly in younger, more affluent groups. Risk of COVID-19 hospital admission was approximately doubled in those with the Delta VOC when compared to the Alpha VOC, with risk of admission particularly increased in those with five or more relevant comorbidities. Both the Oxford–AstraZeneca and Pfizer–BioNTech COVID-19 vaccines were effective in reducing the risk of SARS-CoV-2 infection and COVID-19 hospitalisation in people with the Delta VOC, but these effects on infection appeared to be diminished when compared to those with the Alpha VOC. We had insufficient numbers of hospital admissions to compare between vaccines in this respect. The Oxford–AstraZeneca vaccine appeared less effective than the Pfizer–BioNTech vaccine in preventing SARS-CoV-2 infection in those with the Delta VOC. Given the observational nature of these data, estimates of vaccine effectiveness need to be interpreted with caution.
June 21, 2021
COVID-19 Vaccination Coverage Among Adults — United States, December 14, 2020–May 22, 2021
By May 22, 2021, 57.0% of U.S. adults aged ≥18 years had received ≥1 vaccine dose; coverage was lower and increased more slowly over time among younger adults. If the current rate of vaccination continues through August, coverage among young adults will remain substantially lower than among older adults.
Overall, 34% of adults aged 18–39 years reported having received a COVID-19 vaccine. Adults aged 18–24 years, as well as non-Hispanic Black adults and those with less education, no insurance, and lower household incomes, had the lowest reported vaccination coverage and intent to get vaccinated. Concerns about vaccine safety and effectiveness were commonly cited barriers to vaccination.
Assessing the Association Between Social Gatherings and COVID-19 Risk Using Birthdays
This study suggests that events that lead to small and informal social gatherings, such as birthdays, and in particular, children’s birthdays, are a potentially important source in SARS-CoV-2 transmission.
June 18, 2021
In this study of people with HIV, ChAdOx1 nCoV-19 was safe and immunogenic, supporting vaccination for those well controlled on ART.
June 17, 2021
mRNA Covid-19 Vaccines in Pregnant Women
After Emergency Use Authorization was granted for the messenger RNA (mRNA) vaccines BNT162b2 (Pfizer–BioNTech) and mRNA-1273 (Moderna), persons at the highest risk for coronavirus disease 2019 (Covid-19)–related illness and death were prioritized for vaccination.
June 16, 2021
Tofacitinib in Patients Hospitalized with Covid-19 Pneumonia
Among patients hospitalized with Covid-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than placebo.
Multisystem Inflammatory Syndrome in Children — Initial Therapy and Outcomes
Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone.
Treatment of Multisystem Inflammatory Syndrome in Children
We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue.
Immunotherapy for MIS-C — IVIG, Glucocorticoids, and Biologics
Since the sudden emergence of multisystem inflammatory disease in children (MIS-C) in April 2020 as a novel and severe presentation of coronavirus disease 2019 (Covid-19), nearly 4000 cases of MIS-C and 35 deaths have been reported in the United States and many more internationally.
We found that the lipid mediators, elovanoid (ELV)-N32 or Resolvin D6-isomer (RvD6i) decreased the expression of the ACE2 receptor, furin, and integrins in damaged corneas or IFNγ-stimulated HCEC. There was also a concomitant decrease in the binding of Spike RBD with the lipid treatments. Using RNA-seq analysis, we uncovered that the lipid mediators also attenuated the expression of pro-inflammatoy cytokines participating in hyper-inflammation and senescence programming. Thus, the bioactivity of these lipid mediators will contribute to open therapeutic avenues to counteract virus attachment and entrance to the body.
An ACE2 Triple Decoy that neutralizes SARS-CoV-2 shows enhanced affinity for virus variants
The ACE2 Triple Decoy maintains high affinity for mutated S RBD, displays enhanced affinity for S RBD N501Y or L452R, and has the highest affinity for S RBD with both E484K and N501Y mutations, making it a viable therapeutic option for the prevention or treatment of SARS-CoV-2 infection with a high likelihood of efficacy against variants.
June 15, 2021
As of May 8, 2021, 16.3% of pregnant women identified in CDC’s Vaccine Safety Datalink had received ≥1 dose of a COVID-19 vaccine during pregnancy in the United States. Vaccination was lowest among Hispanic (11.9%) and non-Hispanic Black women (6.0%) and women aged 18–24 years (5.5%) and highest among non-Hispanic Asian women (24.7%) and women aged 35–49 years (22.7%).
June 14, 2021
Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection
Vaccination increases all components of the humoral response and, as expected, results in serum neutralizing activities against variants of concern similar to or greater than the neutralizing activity against the original Wuhan Hu-1 strain achieved by vaccination of naive individuals. The mechanism underlying these broad-based responses involves ongoing antibody somatic mutation, memory B cell clonal turnover and development of monoclonal antibodies that are exceptionally resistant to SARS-CoV-2 RBD mutations, including those found in the variants of concern4,9. In addition, B cell clones expressing broad and potent antibodies are selectively retained in the repertoire over time and expand markedly after vaccination. The data suggest that immunity in convalescent individuals will be very long lasting and that convalescent individuals who receive available mRNA vaccines will produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants.
June 10, 2021
The pro-homeostatic lipid mediators elovanoids (ELVs) attenuate cell binding and entrance of the SARS-CoV-2 receptor-binding domain (RBD) as well as of the SARS-CoV-2 virus in human primary alveoli cells in culture. We uncovered that very-long-chain polyunsaturated fatty acid precursors (VLC-PUFA, n-3) activate ELV biosynthesis in lung cells. Both ELVs and their precursors reduce the binding to RBD.
June 9, 2021
All patients achieved complete remission. The median [IQR] time to resolution of major symptoms was 18 [14–23] days in the ‘recommended schedule' cohort and 14 [7–30] days in the matched ‘control’ cohort (p = 0·033). Other symptoms persisted in a lower percentage of patients in the ‘recommended’ than in the ‘control’ cohort (23·3% versus 73·3%, respectively, p<0·0001) and for a shorter period (p = 0·0107). Two patients in the ‘recommended’ cohort were hospitalised compared to 13 (14·4%) controls (p = 0·0103). The prevention algorithm reduced the days and cumulative costs of hospitalisation by >90%.
June 8, 2021
Breathing, speaking, coughing or sneezing: What drives transmission of SARS-CoV-2?
The abundance of this speech-generated aerosol, combined with its high viral load in pre- and asymptomatic individuals, strongly implicates airborne transmission of SARS-CoV-2 through speech as the primary contributor to its rapid spread.
Our findings show MIS-C is distinguishable from Kawasaki disease primarily by elevated CXCL9 concentrations. The stratification of patients with MIS-C by high or low CXCL9 concentrations provides support for MAS-like pathophysiology in patients with severe MIS-C, suggesting new approaches for diagnosis and management.
How COVID-19 Can Lead to Diabetes
Along with the pneumonia, blood clots, and other serious health concerns caused by SARS-CoV-2, the COVID-19 virus, some studies have also identified another troubling connection. Some people can develop diabetes after an acute COVID-19 infection.
By May 1, 2021, 82%, 63%, and 42% of adults aged ≥65, 50–64, and 18–49 years, respectively, had received ≥1 vaccine dose. From November 29–December 12, 2020 to April 18–May 1, 2021, the rate ratios of COVID-19 incidence, emergency department visits, hospital admissions, and deaths among adults aged ≥65 years (≥70 years for hospitalizations) to adults aged 18–49 years declined 40%, 59%, 65%, and 66%, respectively.
The presence of CNS hyperintense lesions or leptomeningeal enhancement on neuroimaging from patients with COVID-19 is associated with increased likelihood of a positive CSF SARS-CoV-2 PCR. However, a positive CSF SARS-CoV-2 PCR is uncommon in patients with these neuroimaging findings, suggesting they are often related to other etiologies, such as inflammation, hypoxia, or ischemia.
A versatile reverse genetics platform for SARS-CoV-2 and other positive-strand RNA viruses
Transfection of the circular cDNA into mammalian cells results in the recovery of infectious SARS-CoV-2 virus that exhibits properties comparable to the parental virus in vitro and in vivo. CPER is also used to generate insect-specific Casuarina virus with ~20 kb genome and the human pathogens Ross River virus (Alphavirus) and Norovirus (Calicivirus), with the latter from a clinical sample. Additionally, reporter and mutant viruses are generated and employed to study virus replication and virus-receptor interactions.
SARS-CoV-2 emerging variants in Africa: view from Gabon
Since SARS-CoV-2 appeared in late 2019 in Wuhan, China, variants have emerged around the world. The general concern is that these variants appear to cause more severe disease, spread more easily between humans, and might change the effectiveness of current treatment and vaccines.
Senolytics reduce coronavirus-related mortality in old mice
Old mice acutely infected with pathogens that included a SARS-CoV-2-related mouse β-coronavirus experienced increased senescence and inflammation with nearly 100% mortality. Targeting SnCs using senolytic drugs before or after pathogen exposure significantly reduced mortality, cellular senescence, and inflammatory markers and increased anti-viral antibodies. Thus, reducing the SnC burden in diseased or aged individuals should enhance resilience and reduce mortality following viral infection, including SARS-CoV-2.
At initial presentation, when it is unclear whether a patient with excessive hyperferritinaemic inflammation has primary HLH, infection-associated secondary HLH, or MAS, high serum concentrations of S100A12 indicate an initial differential diagnosis of systemic JIA-MAS, thus helping to guide subsequent treatment decisions. We therefore suggest the inclusion of serum S100A12 and IL-18 in the diagnostic investigations for hyperferritinaemic syndromes; however, the definition and introduction of universially applicable cutoff values are still required.
Application of intravenous umbilical cord mesenchymal stromal cell infusion as an adjuvant treatment for critically ill patients with COVID-19 increases the survival rate by modulating the immune system toward an anti-inflammatory state.
Mitigating airborne transmission of SARS-CoV-2
Ventilation is a key mitigation measure against airborne transmission, and recommendations and funding should be provided to business and schools for assessments and upgrades.
Portal vein thrombosis associated with ChAdOx1 nCov-19 vaccination
A 41-year-old man with an unremarkable medical history presented to the emergency department with a headache that woke him and persisted despite painkillers. He had no neurological symptoms. The initial evaluation revealed severe thrombocytopenia (64 000 per μL) and increased D-dimer (42 028 μg/L). Cranial CT identified no findings of haematoma or ischaemia, and there was no sign of dural venous thrombosis on CT angiography.
Epidemiology, not geopolitics, should guide COVID-19 vaccine donations
With COVID-19 vaccine supplies shifting from scarcity to abundance in high-income settings, such as Canada, the EU, the USA, and the UK, the June 11–13, 2021, Group of Seven (G7) summit in Cornwall, UK, is the time when leaders from those countries should act on their promises to send surplus COVID-19 vaccine supplies to the many other countries where doses remain scarce.
Contextualising evidence-based recommendations for the second wave of the COVID-19 pandemic in India
During the second wave of the COVID-19 pandemic in India, which began in March, 2021, demand on the health-care system has far exceeded capacity. Despite crippling shortages, patients are prescribed a battery of ineffective therapeutic interventions.1 Ivermectin, hydroxychloroquine, and herbal cocktails continue to receive state patronage.
Deciphering the cytokine fingerprint of macrophage activation syndrome
Combatting cytokine storm syndromes is an increasingly frequent challenge faced by paediatric rheumatologists. The rising rate of encounters with these conditions is due in part to heightened awareness of paediatric hyperinflammatory syndromes coupled with an expanding armamentarium of anticytokine therapies that practitioners in our field can wield effectively.
June 5, 2021
Necessity of COVID-19 vaccination in previously infected individuals
Individuals who have had SARS-CoV-2 infection are unlikely to benefit from COVID-19 vaccination, and vaccines can be safely prioritized to those who have not been infected before.
June 4, 2021
COVID-19 adolescent hospitalization rates from COVID-NET peaked at 2.1 per 100,000 in early January 2021, declined to 0.6 in mid-March, and rose to 1.3 in April. Among hospitalized adolescents, nearly one third required intensive care unit admission, and 5% required invasive mechanical ventilation; no associated deaths occurred.
June 3, 2021
Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination
Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.)
Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination
We report findings in five patients who presented with venous thrombosis and thrombocytopenia 7 to 10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against coronavirus disease 2019 (Covid-19). The patients were health care workers who were 32 to 54 years of age. All the patients had high levels of antibodies to platelet factor 4–polyanion complexes; however, they had had no previous exposure to heparin. Because the five cases occurred in a population of more than 130,000 vaccinated persons, we propose that they represent a rare vaccine-related variant of spontaneous heparin-induced thrombocytopenia that we refer to as vaccine-induced immune thrombotic thrombocytopenia.
This randomized phase 3 clinical trial included 966 participants who were residents and staff at US skilled nursing and assisted living facilities with at least 1 confirmed SARS-CoV-2 index case and who were negative at baseline for SARS-CoV-2 infection and serology, enrolled from August to November 2020. The incidence of COVID-19 infection among those treated with bamlanivimab vs placebo was 8.5% vs 15.2%, respectively, a difference that was statistically significant.
Bamlanivimab for Prevention of COVID-19
Passive immunotherapy has played an essential role in the prevention and treatment of infectious diseases since Emil von Behring’s Nobel Prize–winning work in the 1890s on the use of antiserum raised in horses to treat diphtheria. This work paved the way for use of antiserum to treat tetanus and prevent rabies, and for Rufus Cole’s development of type-specific immune serum to treat pneumococcal pneumonia, published in 1913.
Could Statins Do More Than Lower Cholesterol in Patients With COVID-19?
Practically every day this spring, New York University cardiologist Aakriti Gupta, MD, MS, has received a phone call from friends or relatives in India who have COVID-19.
June 2, 2021
In contrast to the initial COVID-19 surge during March to April 2020 in the US and to recent data from the UK, no significant declines in AMI hospitalization or stroke alerts were observed during the largest and most recent surge during October 2020 to January 2021 in KPNC. A modest decline was observed for stroke alerts during the summer COVID-19 surge but quickly rebounded. Study limitations include an inability to delineate specific reasons for observed declines in AMI and stroke alerts and potential lack of generalizability to other regions or systems. These patterns may reflect changing patient attitudes during the COVID-19 pandemic or the success of health system and public health campaigns to reassure patients about the safety of seeking emergency care when needed.
June 1, 2021
Studies Confirm COVID-19 mRNA Vaccines Safe, Effective for Pregnant Women
Clinical trials have shown that COVID-19 vaccines are remarkably effective in protecting those age 12 and up against infection by the coronavirus SARS-CoV-2. The expectation was that they would work just as well to protect pregnant women. But because pregnant women were excluded from the initial clinical trials, hard data on their safety and efficacy in this important group has been limited.
May 28, 2021
Early Covid-19 Treatment With SARS-CoV-2 Neutralizing Antibody Sotrovimab
Sotrovimab reduced progression of Covid-19 in patients with mild/moderate disease, was well tolerated, and no safety signals were identified.
Disparities in county-level vaccination coverage by social vulnerability have increased as vaccine eligibility has expanded, especially in large fringe metropolitan (areas surrounding large cities, e.g., suburban) and nonmetropolitan counties. By May 1, 2021, vaccination coverage among adults was lower among those living in counties with lower socioeconomic status and with higher percentages of households with children, single parents, and persons with disabilities.
In most cases, patients who presented for medical care have responded well to medications and rest and had prompt improvement of symptoms. Reported cases have occurred predominantly in male adolescents and young adults 16 years of age and older. Onset was typically within several days after mRNA COVID-19 vaccination, and cases have occurred more often after the second dose than the first dose. CDC and its partners are investigating these reports of myocarditis and pericarditis following mRNA COVID-19 vaccination.
KFF COVID-19 Vaccine Monitor: May 2021
The latest KFF COVID-19 Vaccine Monitor shows continued steady progress in vaccine uptake, with 62% of U.S. adults saying they’ve gotten at least one dose of a vaccine (up from 56% in April) and the share saying they will “wait and see” down slightly from 15% to 12%. This leaves few remaining eager to get vaccinated, while the shares saying they will get vaccinated “only if required” (7%) or will “definitely not” get a vaccine (13%) essentially unchanged over the last several months. Yet findings also suggest the overall adult vaccination rates could reach 70% over the next several months, with 4% saying they want the vaccine as soon as possible and about a third of the “wait and see group” (or 4% of all adults) saying they have already scheduled an appointment or plan to get the vaccine in the next 3 months.
May 27, 2021
Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents
Until very recently, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had not been authorized for emergency use in persons younger than 16 years of age. Safe, effective vaccines are needed to protect this population, facilitate in-person learning and socialization, and contribute to herd immunity.
In community-treated patients including those without a mandatory diagnostic test, the effect of colchicine on COVID-19-related clinical events was not statistically significant. Among patients with PCR-confirmed COVID-19, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Given the absence of orally administered therapies to prevent COVID-19 complications in community-treated patients and the benefit of colchicine in patients with PCR-proven COVID-19, this safe and inexpensive anti-inflammatory agent could be considered for use in those at risk of complications. Notwithstanding these considerations, replication in other studies of PCR-positive community-treated patients is recommended.
The SARS-CoV-2 B.1.617 lineage emerged in October 2020 in India. It has since then become dominant in some indian regions and further spread to many countries. The lineage includes three main subtypes (B1.617.1, B.1617.2 and B.1.617.3), which harbour diverse Spike mutations in the Nterminal domain (NTD) and the receptor binding domain (RBD) which may increase their immune evasion potential. B.1.617.2 is believed to spread faster than the other versions. Here, we isolated infectious B.1.617.2 from a traveller returning from India. We examined itssensitivity to monoclonal antibodies (mAbs) and to antibodies present in sera from COVID-19 convalescent individuals or vaccine recipients, in comparison to other viral lineages. B.1.617.2 was resistant to neutralization by some anti-NTD and anti-RBD mAbs, including Bamlanivimab, which were impaired in binding to the B.1.617.2 Spike.
May 26, 2021
Incentives for Immunity — Strategies for Increasing Covid-19 Vaccine Uptake
The once-promising pace of Covid-19 vaccination in the United States has slowed, from a peak of 3.38 million shots on April 13, 2021, to fewer than 2 million doses per day in May. Until recently, Americans were competing for limited vaccination slots — a situation that raised equity concerns — but now supply exceeds demand in much of the country, and mass vaccination clinics are closing.
Longitudinal immune dynamics of mild COVID-19 define signatures of recovery and persistence
We characterized signals associated with recovery and convalescence to define a new signature of inflammatory cytokines, gene expression, and chromatin accessibility that persists in individuals with post-acute sequelae of SARS-CoV-2 infection (PASC).
Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults
This prespecified interim analysis of a randomized clinical trial included 40 382 participants who received at least 1 dose of a 2-dose inactivated vaccine series developed from either SARS-CoV-2 WIV04 (5 µg/dose) or HB02 (4 µg/dose) strains or an aluminum hydroxide–only control, with a primary end point of the incidence of symptomatic COVID-19 at least 14 days after the second injection. The efficacy for the 2 vaccines, compared with an aluminum hydroxide–only control, was 72.8% in the WIV04 group and 78.1% in the HB02 group; both comparisons were statistically significant.
May 25, 2021
This study suggests that bitter taste receptor allelic variants are associated with innate immune fitness toward SARS-CoV-2 and can be used to correlate with clinical course and prognosis of COVID-19.
COVID-19 Vaccine Breakthrough Infections Reported to CDC — United States, January 1–April 30, 2021
As of April 30, 2021, approximately 101 million persons in the United States had been fully vaccinated against COVID-19. However, during the surveillance period, SARS-CoV-2 transmission continued at high levels in many parts of the country, with approximately 355,000 COVID-19 cases reported nationally during the week of April 24–30, 2021. Even though FDA-authorized vaccines are highly effective, breakthrough cases are expected, especially before population immunity reaches sufficient levels to further decrease transmission. However, vaccine breakthrough infections occur in only a small fraction of all vaccinated persons and account for a small percentage of all COVID-19 cases. The number of COVID-19 cases, hospitalizations, and deaths that will be prevented among vaccinated persons will far exceed the number of vaccine breakthrough cases. To date, the age and sex distribution of reported vaccine breakthrough infections reflects the fully vaccinated U.S. population. The proportion of reported vaccine breakthrough infections attributed to variants of concern has also been similar to the proportion of these variants circulating throughout the United States. During March 28–April 10, 2021, the aforementioned variants of concern accounted for 70% of the weighted estimates of SARS-CoV-2 lineages submitted to CDC’s national genomic surveillance.
Patients with rheumatic and musculoskeletal diseases (RMDs) are at increased risk for SARS-CoV-2 infection because of both the immunomodulatory effects of their underlying diseases and treatment with immunosuppressive agents.
May 21, 2021
COVID-19 incidence was 37% lower in schools that required teachers and staff members to use masks and 39% lower in schools that improved ventilation. Ventilation strategies associated with lower school incidence included dilution methods alone (35% lower incidence) or in combination with filtration methods (48% lower incidence).
Utah implemented two high school COVID-19 testing programs to sustain in-person instruction and extracurricular activities. During November 30, 2020–March 20, 2021, among 59,552 students who received testing, 1,886 (3.2%) had a positive result. These programs facilitated the completion of approximately 95% of high school extracurricular competition events and saved an estimated 109,752 in-person instruction student-days.
May 20, 2021
Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant
A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant.
Increased axillary lymph node or ipsilateral deltoid uptake is occasionally observed on FDG or 11C-choline PET performed after Pfizer-BioNTech or Moderna COVID-19 vaccination.
May 19, 2021
Quantitative RT-PCR (RT-qPCR) of nasopharyngeal swab (NPS) samples for SARS-CoV-2 detection requires medical personnel and is time consuming, and thus is poorly suited to mass screening. In June, 2020, a chemiluminescent enzyme immunoassay (CLEIA; Lumipulse G SARS-CoV-2 Ag kit, Fujirebio, Tokyo, Japan) was developed that can detect SARS-CoV-2 nucleoproteins in NPS or saliva samples within 35 min. In this study, we assessed the utility of CLEIA in mass SARS-CoV-2 screening.
PF4 Immunoassays in Vaccine-Induced Thrombotic Thrombocytopenia
Our results provide further support to show that rapid immunoassays should be avoided in the detection of PF4-specific antibodies in patients with suspected VITT. Therefore, the use of a sensitive, quantitative, immunologic test is strongly recommended, because according to the recently proposed algorithm, nonheparin anticoagulants should be preferred when clinically significant levels of anti-PF4 antibodies are detected.
Incident SARS-CoV-2 Infection among mRNA-Vaccinated and Unvaccinated Nursing Home Residents
Across all the study groups, most infections were asymptomatic, and the incidence of both asymptomatic and symptomatic infections decreased. Nursing homes that were located in counties with the highest incidence of SARS-CoV-2 infection had the most incident cases but still had large decreases. We observed inconsistent patterns in the incidence of infection among residents relative to rates of vaccination among staff members.
Diverse Functional Autoantibodies in Patients with COVID-19
Analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics and disease severity. In summary, these findings implicate a pathological role for exoproteome-directed autoantibodies in COVID-19 with diverse impacts on immune functionality and associations with clinical outcomes.
The goal of this cohort study was to describe the spectrum of MIS-A presentation after SARS-CoV-2 infection. We identified cases of MIS-A among all adults with laboratory-proven subacute or convalescent SARS-CoV-2 infection at a single tertiary care medical center and described their clinical characteristics and outcomes.
The COVID-19 pandemic has upended our societal status quo. SARS-CoV-2, the virus responsible for COVID-19, has led to a myriad of clinical presentations, many of which were different from the diseases caused by other respiratory viral infections. Among the manifestations were olfactory dysfunction and so-called COVID toes, leading to a constant change of what we understood as the spectrum of illness caused by SARS-CoV-2. To help understand this complex clinical picture, a framework for the spectrum of SARS-CoV-2 infection has been proposed. Now, more than a year after the initial discovery of COVID-19, that complete clinical picture continues to be evasive as new features of SARS-CoV-2 are described.
In this cohort study of 18 148 individuals whose vitamin D levels were measured before the COVID-19 pandemic, low levels of vitamin D were associated with SARS-CoV-2 seropositivity in unadjusted univariable analysis. However, after adjusting for potentially confounding factors, including age, sex, race/ethnicity, education, body mass index, blood pressure, smoking status, and geographical location, vitamin D level was not associated with SARS-CoV-2 seropositivity.
Consumer Views on Using Digital Data for COVID-19 Control in the United States
In this cross-sectional survey study of 6284 US adults, approval was generally low for use of consumer digital data for activities such as case identification, digital contact tracing, policy setting, and enforcing quarantines. Political ideology and race/ethnicity were associated with approval for scenarios in which digital data were used, whereas local COVID-19 incidence and family experience with COVID were not.
May 18, 2021
Pharmacological activation of STING blocks SARS-CoV-2 infection
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic, resulting millions of infections and deaths with few effective interventions available. Here, we demonstrate that SARS-CoV-2 evades interferon (IFN) activation in respiratory epithelial cells, resulting in a delayed response in bystander cells. Since pretreatment with IFNs can block viral infection, we reasoned that pharmacological activation of innate immune pathways could control SARS-CoV-2 infection.
These data indicate that in the first year since the start of community transmission, seropositivity levels in metropolitan in Stockholm had reached approximately one in five persons, providing important baseline seroprevalence information prior to the start of vaccination.
COVID-19 vaccination coverage was lower in rural counties (38.9%) than in urban counties (45.7%); disparities persisted among age groups and by sex.
Rare PEG Allergy Triggered Postvaccination Anaphylaxis
Researchers in the UK have linked anaphylaxis in a patient who received the Pfizer-BioNTech COVID-19 vaccine with her allergy to polyethylene glycol (PEG), which stabilizes lipid nanoparticles that deliver mRNA in the vaccine to cells in the body.
May 17, 2021
Our carefully tracked interval data indicate that a group of school-aged children, most of whom had ASD and/or ADHD, were capable of face covering across activities. Our findings are consistent with recent reports of face covering in school-aged children6 but included direct observation and extended to children with greater special education needs. Limitations include a small sample size, a high staff to child ratio, no data on prior masking behavior, and no interrater reliability. As policy makers and school personnel consider plans for in-person activities, face covering can be used as part of a constellation of practices to reduce the transmission of SARS-CoV-2 in pediatric settings.
In this cohort study of 478 US hospitals with 324 013 patients with IS, substantial decreases in the number of patients discharged with IS were observed at the beginning of the pandemic in February 2020, but these rates returned to prepandemic levels by July 2020. Compared with patients with IS in 2019, those with IS and comorbid COVID-19 in 2020 were less likely to have conventional vascular risk factors or stroke at hospital admission and were more likely to be Black or Hispanic and to experience medical complications and in-hospital death.
May 14, 2021
The first U.S. multisite test-negative design vaccine effectiveness study among HCP found a single dose of Pfizer-BioNTech or Moderna COVID-19 vaccines to be 82% effective against symptomatic COVID-19 and 2 doses to be 94% effective.
On May 12, 2021, after a systematic review of all available data, the Advisory Committee on Immunization Practices made an interim recommendation for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12–15 years for the prevention of COVID-19.
By combining predicted affinities and available antibody escape data, we show that fast-spreading viral variants exploit combinatorial mutations possessing both enhanced affinity and antibody resistance, including S477N/E484K, E484K/N501Y and K417T/E484K/N501Y. Thus, three-dimensional modeling of the Spike/hACE2 complex predicts changes in structure and binding affinity that correlate with transmissibility and therefore can help inform future intervention strategies.
This qualitative study evaluated 82 submissions to a university open call for creative solutions from students, faculty, and staff to inform safety in the fall 2020 semester. Solutions were shared with university leadership, and several are being further developed.
The rocky road to universal COVID-19 vaccination
As of May 9, 2021, the COVID-19 pandemic has caused 3 277 272 deaths and disrupted the lives of billions of people. Global equitable access to COVID-19 vaccines is the only way to mitigate the public health and economic impact of the pandemic. That is why 1 year ago the COVAX scheme, co-led by the Coalition for Epidemic Preparedness Innovations, Gavi, the Vaccine Alliance, and WHO, was set up to try to ensure fair access to vaccines, by guaranteeing that each country would receive vaccine doses for at least 20% of its population.
May 13, 2021
Interim Results of a Phase 1–2a Trial of Ad26.COV2.S Covid-19 Vaccine
The safety and immunogenicity profiles of Ad26.COV2.S support further development of this vaccine candidate.
Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women
In this cohort study involving 103 women who received a COVID-19 mRNA vaccine, 30 of whom were pregnant and 16 of whom were lactating, immunogenicity was demonstrated in all, and vaccine-elicited antibodies were found in infant cord blood and breast milk. Pregnant and nonpregnant vaccinated women developed cross-reactive immune responses against SARS-CoV-2 variants of concern.
May 12, 2021
BNT162b2-Elicited Neutralization against New SARS-CoV-2 Spike Variants
Because these data show that the newly emerged B.1.526, B.1.429, and B.1.1.7+E484K variants remain susceptible to an important vaccine-elicited immune effector (neutralizing antibody), they confirm the importance of mass immunization with current, highly effective, authorized vaccines as a central strategy to end the Covid-19 pandemic.
Perinatal Outcomes During the COVID-19 Pandemic in Ontario, Canada
Public health measures to control the COVID-19 pandemic may be associated with reduced risk of preterm birth (PTB).1,2 Conversely, avoidance of health care may be associated with increased risk of stillbirth.3 We evaluated rates of PTB and stillbirth during the first 6 months of the pandemic because previous studies conducted early in the pandemic have had inconsistent results.
Delayed Localized Hypersensitivity Reactions to the Moderna COVID-19 Vaccine
The Moderna COVID-19 vaccine may cause a delayed localized hypersensitivity reaction with a median latency to onset of 7 days after vaccine administration. This pruritic and variably tender reaction has a median duration of 5 days, but may persist for up to 21 days, and may occur again and sooner after the second vaccine dose; no serious adverse events were observed in association with this cutaneous reaction to the Moderna COVID-19 vaccine.
The Covid-19 Infodemic — Applying the Epidemiologic Model to Counter Misinformation
Throughout the world, including the United States, medical professionals and patients are facing both a pandemic and an infodemic — the first caused by SARS-CoV-2 and the second by misinformation and disinformation.
May 11, 2021
Reversed-engineered human alveolar lung-on-a-chip model
This work reports the development of a physiologically relevant human alveolar lung-on-a-chip model, composed of a three-dimensional (3D) porous hydrogel made of gelatin methacryloyl (GelMA) featuring an inverse opal structure, bonded to a compartmentalized chip device that provides air–liquid interface and cyclic breathing motions. Significantly, this GelMA structure has a high similarity to native human alveolar sacs in that they both possess sac-like pores and interconnecting windows between the sacs, in addition to a stiffness similar to the native human distal lung. We showed through multiscale analyses that our 3D GelMA inverse opal structure was better able to maintain the functions of primary human alveolar epithelial cells in a more in vivo-like manner compared with planar models.
May 8, 2021
COVID-19 has completely changed our daily clinical practice as well as our social relations. Many organs and biological systems are involved in SARS-Cov-2 infection, either due to direct virus-induced damage or to indirect effects that can have systemic consequences. Endocrine system is not only an exception but its involvement in COVID-19 is so relevant that an “endocrine phenotype” of COVID-19 has progressively acquired clinical relevance.
May 7, 2021
In a multistate network of U.S. hospitals during January–March 2021, receipt of Pfizer-BioNTech or Moderna COVID-19 vaccines was 94% effective against COVID-19 hospitalization among fully vaccinated adults and 64% effective among partially vaccinated adults aged ≥65 years.
May 6, 2021
In this retrospective cohort study conducted in Tel Aviv, Israel, that included 6710 health care workers who underwent periodic testing for SARS-CoV-2 infection, vaccination with the BNT162b2 vaccine was associated with an adjusted incidence rate ratio of 0.03 for symptomatic infection and 0.14 for asymptomatic infection more than 7 days after the second dose. Both incidence rate ratios were statistically significant.
The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity
Some similarities exist between COVID-19 and respiratory failure of other origins, but evidence for many distinctive mechanistic features indicates that COVID-19 constitutes a new disease entity, with emerging data suggesting involvement of an endotheliopathy-centred pathophysiology. Further research, combining basic and clinical studies, is needed to advance understanding of pathophysiological mechanisms and to characterise immuno-inflammatory derangements across the range of phenotypes to enable optimum care for patients with COVID-19.
May 5, 2021
Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens progress toward control of the coronavirus disease 2019 (Covid-19) pandemic. In a phase 1–2 trial involving healthy adults, the NVX-CoV2373 nanoparticle vaccine had an acceptable safety profile and was associated with strong neutralizing-antibody and antigen-specific polyfunctional CD4+ T-cell responses. Evaluation of vaccine efficacy was needed in a setting of ongoing SARS-CoV-2 transmission.
Interplay between Emerging SARS-CoV-2 Variants and Pandemic Control
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of a diverse family of enveloped, nonsegmented RNA viruses. The coronavirus genomic RNA is unusually large, the RNA polymerase is error-prone, and mutations accumulate with increasing frequency during infections. With continued uncontrolled transmission and viral replication, mutations that give the virus a fitness advantage will emerge. A SARS-CoV-2 variant of concern has one or more mutations that confer worrisome epidemiologic, immunologic, or pathogenic properties.
Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants
The messenger RNA vaccine BNT162b2 (Pfizer–BioNTech) has 95% efficacy against coronavirus disease 2019 (Covid-19).1 Qatar launched a mass immunization campaign with this vaccine on December 21, 2020. As of March 31, 2021, a total of 385,853 persons had received at least one vaccine dose and 265,410 had completed the two doses.
Two doses of BNT162b2 are highly effective across all age groups (≥16 years, including older adults aged ≥85 years) in preventing symptomatic and asymptomatic SARS-CoV-2 infections and COVID-19-related hospitalisations, severe disease, and death, including those caused by the B.1.1.7 SARS-CoV-2 variant. There were marked and sustained declines in SARS-CoV-2 incidence corresponding to increasing vaccine coverage. These findings suggest that COVID-19 vaccination can help to control the pandemic.
Missing the Point — How Primary Care Can Overcome Covid-19 Vaccine “Hesitancy”
By the end of April 2021, the United States had fully vaccinated just under a third of its population against Covid-19. Initial federal and state vaccination strategies focused on hospitals, mass-vaccination centers, and retail pharmacies, quickly vaccinating health care workers and residents of long-term care facilities who were at high risk for Covid-19.
The NYC Department of Health and Mental Hygiene analyzed laboratory and epidemiologic data to characterize cases of B.1.526 infection and the associated potential for breakthrough infection and reinfection. Preliminary evidence suggests that, to date, B.1.526 does not lead to more severe disease or increased risk for infection after vaccination.
The B.1.427 and B.1.429 variants of SARS-CoV-2, the virus that causes COVID-19, were first described in Southern California on January 20, 2021 (1); on March 16 they were designated variants of concern* (2). Data on these variants are limited, but initial reports suggest that, compared with other lineages, they might be more infectious (1,2), cause more severe illness (2), and be less susceptible to neutralizing monoclonal antibody products such as bamlanivimab, an investigational treatment for mild-to-moderate COVID-19 (1–3). On January 24, the Colorado Department of Public Health and Environment (CDPHE) identified the first Colorado case of COVID-19 attributed to these variants. B.1.427 and B.1.429 were considered a single variant described as CAL.20C or B.1.427/B.1.429 in the 20C clade (1,3); in this report “B.1.427/B.1.429” refers to B.1.427 or B.1.429 lineage, including those reported as B.1.427/B.1.429 without further differentiation.
Data from six models indicate that with high vaccination coverage and moderate NPI adherence, hospitalizations and deaths will likely remain low nationally, with a sharp decline in cases projected by July 2021. Lower NPI adherence could lead to substantial increases in severe COVID-19 outcomes, even with improved vaccination coverage.
Researchers Tie Severe Immunosuppression to Chronic COVID-19 and Virus Variants
Last summer, a UK man in his 70s was admitted to Addenbrooke’s Hospital in Cambridge with COVID-19 pneumonia. He hadn’t been able to shake his illness since testing positive for SARS-CoV-2 more than a month earlier. Despite interventions including multiple rounds of the antiviral remdesivir and convalescent plasma, he died in the hospital’s intensive care unit about 9 weeks after his arrival.
May 3, 2021
The rapid repurposing of antivirals is particularly pressing during pandemics. However, rapid assays for assessing candidate drugs typically involve in vitro screens and cell lines that do not recapitulate human physiology at the tissue and organ levels. Here we show that a microfluidic bronchial-airway-on-a-chip lined by highly differentiated human bronchial-airway epithelium and pulmonary endothelium can model viral infection, strain-dependent virulence, cytokine production and the recruitment of circulating immune cells.
In this cohort study, generally low rates of coronavirus testing were observed in 2679 participants reporting new onset of febrile illness. Although testing rates improved somewhat during the study period, timely coronavirus test results were sought and received by only 25.9% of newly febrile persons at the end of the study analysis period in late October 2020.
In this cross-sectional study of 397 children and youths with COVID-19 in the first 3 waves of outbreaks in Hong Kong, in 2020, the largest group had no recent international travel, and nearly all individuals were reported to have other family members with COVID-19. Three students studying in the same school contracted COVID-19, and few children or youths with no recent international travel reported unknown contact histories.
In this cohort study of 20 736 patients, in-hospital mortality rates decreased in the US between March and November 2020, even after accounting for the changing mix in patient age, sex, comorbidities, and disease severity at the time of admission. Hospital and intensive care unit length of stay and use of mechanical ventilation decreased over time, whereas the use of glucocorticoids and remdesivir increased.
Association Between Income Inequality and County-Level COVID-19 Cases and Deaths in the US
This ecological cohort study found that there was a positive correlation between Gini coefficients and county-level COVID-19 cases and deaths during the study period. The association between income inequality and COVID-19 cases and deaths varied over time and was strongest in the summer months of 2020.
May 1, 2021
In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids.
April 30, 2021
Five mass vaccination sites reported 64 anxiety-related events, including 17 events of syncope (fainting) after receipt of Janssen COVID-19 vaccine. The reporting rates of syncope to VAERS after Janssen COVID-19 and influenza vaccines (2019–20) were 8.2 and 0.05 per 100,000 doses, respectively.
By April 21, nearly 8 million doses of the Janssen COVID-19 vaccine had been administered. Review of safety monitoring data found that 97% of reported reactions after vaccine receipt were nonserious, consistent with preauthorization clinical trials data. Seventeen thrombotic events with thrombocytopenia have been reported, including three non-CVST events.
Linked Clusters of SARS-CoV-2 Variant B.1.351 — Maryland, January–February 2021
Investigation identified two linked clusters of SARS-CoV-2 infection, comprising 17 total patients (two were hospitalized and one died) who did not report recent travel. Four patients’ specimens were sequenced; all were the B.1.351 variant.
In this case series of 12 patients, all were women, younger than 60 years, and had symptom onset ranging from 6 to 15 days after vaccination requiring hospitalization. Of 11 patients with heparin-platelet factor 4 enzyme-linked immunosorbent assay (ELISA) heparin-induced thrombocytopenia (HIT) antibody test results, all were positive. At last follow-up, outcomes were death (n = 3), intensive care unit (ICU) care (n = 3), non-ICU hospitalization (n = 2), and discharge to home (n = 4).
Some minority ethnic populations in England have excess risks of testing positive for SARS-CoV-2 and of adverse COVID-19 outcomes compared with the White population, even after accounting for differences in sociodemographic, clinical, and household characteristics. Causes are likely to be multifactorial, and delineating the exact mechanisms is crucial. Tackling ethnic inequalities will require action across many fronts, including reducing structural inequalities, addressing barriers to equitable care, and improving uptake of testing and vaccination.
COVID-19 and disparities affecting ethnic minorities
Longstanding health disparities affecting ethnic minorities in the UK have been made acutely visible by the COVID-19 pandemic. The disproportionate effects of COVID-19 among minority ethnic groups were present from the beginning, with Black and Asian patients in the UK being over-represented among those with COVID-19 receiving advanced respiratory support.
COVID research updates: One vaccine dose can nearly halve transmission risk
Nature wades through the literature on the coronavirus — and summarizes key papers as they appear.
April 29, 2021
Association of Maternal SARS-CoV-2 Infection in Pregnancy With Neonatal Outcomes
Maternal SARS-CoV-2 infection in pregnancy was significantly associated with small increases in the absolute risk of respiratory disorders and some other neonatal morbidities.
Leveraging Open Science to Accelerate Research
The United States has mobilized the full force of its clinical research enterprise to address the Covid-19 pandemic, allocating billions of dollars to support timely research.
Choices in a Crisis — Individual Preferences among SARS-CoV-2 Vaccines
The extraordinarily swift development of effective vaccines against SARS-CoV-2 offers new optimism about combating the Covid-19 pandemic. So far, vaccine demand far exceeds supply, and people generally cannot choose which vaccine they receive. In the United States, this lack of choice has generated little debate given the similar mechanism of action, number of required doses, safety profile, and efficacy of the two vaccines approved in December 2020, both based on mRNA technology.
Respiratory infections, including SARS-CoV-2, are spread via inhalation or ingestion of airborne pathogens. Airborne transmission is difficult to control, particularly indoors. Manufacturers of high efficiency particulate air (HEPA) filters claim they remove almost all small particles including airborne bacteria and viruses. This study investigates whether modern portable, commercially available air filters reduce the incidence of respiratory infections and/or remove bacteria and viruses from indoor air.
A molecular single-cell lung atlas of lethal COVID-19
Respiratory failure is the leading cause of death in patients with severe SARS-CoV-2 infection, yet the host response at the lung tissue-level is poorly understood. Here, we performed single-nucleus RNA-sequencing of ~116,000 nuclei of lungs from 19 COVID-19 decedents who underwent rapid autopsy and 7 control lungs.
Cerebral venous sinus thrombosis (CVST) is a rare manifestation of cerebrovascular disease. Recent reports from the Centers of Disease Control and the U.S. Food and Drug Administration identified six cases of CVST associated with thrombocytopenia in U.S. patients who had received the Ad26.COV2.S (Janssen) Coronavirus disease 2019 (COVID-19) vaccine.
April 28, 2021
In a multistate network of U.S. hospitals during January–March 2021, receipt of Pfizer-BioNTech or Moderna COVID-19 vaccines was 94% effective against COVID-19 hospitalization among fully vaccinated adults and 64% effective among partially vaccinated adults aged ≥65 years.
Assessment of Length and Readability of Informed Consent Documents for COVID-19 Vaccine Trials
These findings suggest that informed consent documents may fail to succinctly explain the studies to participants of all reading levels and that it is possible to improve these documents to increase participant accessibility.
Beyond the First Dose — Covid-19 Vaccine Follow-through and Continued Protective Measures
In December 2020, the United States began an ambitious vaccination program to inoculate Americans against Covid-19. Just a year after the first known Covid case in the United States, more than 40 million Americans had received the first dose of a vaccine developed by Pfizer and BioNTech or one by Moderna. The herculean effort has grappled with immense technological and logistic challenges in developing, producing, and distributing vaccines at unprecedented scale and speed. Its ultimate success, however, hinges on the public’s behavior.
April 27, 2021
On April 23, the Advisory Committee on Immunization Practices concluded that the benefits of resuming Janssen COVID-19 vaccination among persons aged ≥18 years outweighed the risks and reaffirmed its interim recommendation under FDA’s Emergency Use Authorization, which includes a new warning for rare clotting events among women aged 18–49 years.
Reasons for Admissions to US Children’s Hospitals During the COVID-19 Pandemic
Measures to mitigate the COVID-19 pandemic affected children’s access to health services and their physical and mental health. Reductions in hospitalizations for children occurred in 2020 compared with prior years.1 Little is known about the reasons for the decline and whether it varied by patient characteristics.
April 26, 2021
These findings suggest that SARS-CoV-2 clade assignment is an important factor that may aid in estimating patient outcomes.
April 24, 2021
Since the outset of 2020, the COVID-19 pandemic has caused widespread havoc to the lives of millions around the world disrupting families, education, and the employment sector. As of March 26, 2021, the CDC reports over 100 million cases and 2 million deaths worldwide.
April 23, 2021
In this simulation modeling study, identifying 10% to 20% of silent infections among children within 3 days after infection would bring attack rates below 5% if only adults were vaccinated. If silent infections among children remained undetected, achieving the same attack rate would require an unrealistically high vaccination coverage (≥81%) of this age group, in addition to vaccination of adults.
In this cohort study of 255 neonates born to women with positive SARS-CoV-2 test results within 2 weeks before and 72 hours after delivery, 88.2% of newborns were tested for the virus during the birth hospitalization and 2.2% had positive results. A main risk factor for neonatal test result positivity was maternal social vulnerability, and the burden of SARS-CoV-2 exposure on newborn health was associated with preterm delivery, which was prompted by worsening maternal COVID-19 illness.
In this cohort study of 965 patients with and without COVID-19 infection, multivariable modeling showed that COVID-19 positivity was associated with significant mean QTc prolongation from baseline during a 5-day observation period compared with no significant mean QTc change in patients without COVID-19. A greater proportion of patients with COVID-19 infection had incidence of QTc of 500 milliseconds or greater compared with patients without COVID-19 infection.
Among 3,171 nonhospitalized adult COVID-19 patients, 69% had one or more outpatient visits 28–180 days after the diagnosis. Two thirds had a visit for a new primary diagnosis, and approximately one third had a new specialist visit. Symptoms potentially related to COVID-19 were common new visit diagnoses. Visits for these symptoms decreased after 60 days but for some patients continued through 120–180 days.
Airport Traveler Testing Program for SARS-CoV-2 — Alaska, June–November 2020
SARS-CoV-2 testing on arrival in Alaska airports identified 951 SARS-CoV-2 infections, or one per 406 arriving travelers, and might have contributed to Alaska’s low incidence during the summer by reducing opportunities for community transmission at travelers’ destination locations.
One million coronavirus sequences: popular genome site hits mega milestone
GISAID’s impressive effort to understand the spread of COVID-19 has seen scientists upload sequences from most nations on Earth.
April 22, 2021
In this trial that included 685 patients, rates of COVID-19–associated hospitalization in patients treated with hydroxychloroquine or lopinavir-ritonavir were not significantly different compared with those who received placebo.
These findings indicate that human‐to‐cat transmission of SARS‐CoV‐2 occurred during the COVID‐19 pandemic in the UK, with the infected cats developing mild or severe respiratory disease. Given the ability of the new coronavirus to infect different species, it will be important to monitor for human‐to‐cat, cat‐to‐cat and cat‐to‐human transmission.
April 21, 2021
Vaccine Breakthrough Infections with SARS-CoV-2 Variants
Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of clinical concern. In a cohort of 417 persons who had received the second dose of BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna) vaccine at least 2 weeks previously, we identified 2 women with vaccine breakthrough infection. Despite evidence of vaccine efficacy in both women, symptoms of coronavirus disease 2019 developed, and they tested positive for SARS-CoV-2 by polymerase-chain-reaction testing. Viral sequencing revealed variants of likely clinical importance, including E484K in 1 woman and three mutations (T95I, del142–144, and D614G) in both. These observations indicate a potential risk of illness after successful vaccination and subsequent infection with variant virus, and they provide support for continued efforts to prevent and diagnose infection and to characterize variants in vaccinated persons. (Funded by the National Institutes of Health and others.)
Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19
A single dose of Ad26.COV2.S protected against symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection and was effective against severe–critical disease, including hospitalization and death. Safety appeared to be similar to that in other phase 3 trials of Covid-19 vaccines.
Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons
Preliminary findings did not show obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines. However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.
Twenty-two possible breakthrough SARS-CoV-2 infections occurred among fully vaccinated persons ≥14 days after their second dose of COVID-19 vaccine. Two thirds of persons were asymptomatic. A minority of persons with breakthrough infection experienced mild to moderate COVID-19–like symptoms; two COVID-19–related hospitalizations and one death occurred. No facility-associated secondary transmission was identified.
In a COVID-19 outbreak at a Kentucky SNF involving a newly introduced variant to the region, unvaccinated residents and health care personnel (HCP) had 3.0 and 4.1 times the risk of infection as did vaccinated residents and HCP. Vaccine was 86.5% protective against symptomatic illness among residents and 87.1% protective among HCP.
April 20, 2021
Serum biomarker profiles clearly separate COVID‐19 from MAS or sHLH, which questions the significance of systemic hyperinflammation following SARS‐CoV‐2 infection as well as the efficacy of drugs targeting key molecules and pathways specifically associated with systemic cytokine storm conditions in the treatment of COVID‐19.
International student mobilities in a contagion: (Im)mobilising higher education?
Remaking international higher education via digital infrastructure and remote learning can only be successful if it addresses the centrality of embodied and experiential dimensions of learning. Travel restrictions and health concerns may lead to increasing regionalisation of international student mobilities. The rapid digitalisation of universities during the COVID‐19 pandemic may accelerate their further commercialisation and privatisation. Institutions and governments seeking to rebuild international higher education through and after the COVID‐19 pandemic need address social justice and sustainability challenges.
Asymptomatic and symptomatic SARS-CoV-2 infections elicit polyfunctional antibodies.
Antibody functions are correlated, regardless of disease severity. Longitudinal samplings show that antibody functions follow similar kinetics of induction and contraction. Overall, asymptomatic SARS-CoV-2 infection elicits polyfunctional antibodies neutralizing the virus and targeting infected cells.
The three‐dimensional structure of the N‐terminal domain of SARS‐CoV SUD (“macrodomain II”, Mac2) in complex with the middle domain of Paip1, determined by X‐ray crystallography and small‐angle X‐ray scattering, provides insights into the structural determinants of the complex formation. In cellulo, SUD enhances synthesis of viral but not host proteins via binding to Paip1 in pBAC‐SARS‐CoV replicon‐transfected cells. We propose a possible mechanism for stimulation of viral translation by the SUD of SARS‐CoV and SARS‐CoV‐2.
COVID-19 is associated with a decrease in circulating adaptive immune cells expressing the key gut homing marker α4β7 suggesting that these cells are preferentially recruited to extra-intestinal tissues independently of α4β7 or that the systemic immune response against SARS-CoV-2 is at least numerically dominated by extraintestinal, particularly pulmonary, immune cell priming.
April 19, 2021
Our data suggest that recent βCoV infections potentially limit the severity of SARS-CoV-2 infections through mechanisms that do not involve cross-reactive antibodies. Our data are consistent with the emerging hypothesis that cellular immune responses elicited by recent common βCoV infections transiently reduce disease severity following SARS-CoV-2 infections.
Current guidelines recommend continuing biologic therapy in dermatologic patients who have not tested positive for or exhibited signs/symptoms of COVID‐19 and postponing biologic therapy in patients who have tested positive for or exhibited signs/symptoms of COVID‐19.
COVID‐19 vaccine acceptance in pregnant women
The present study reported low acceptance of COVID‐19 vaccination in a sample of pregnant women. Concern about vaccine safety was the major hesitancy reason. Identifying attitudes among priority groups will be useful to create vaccination strategies in the prevention current pandemic.
COVID-19 Vaccination Preparedness Policies in U.S. Hospitals
We surveyed infectious disease specialists about early COVID-19 vaccination preparedness. Almost all respondents’ institutions rated their facility’s preparedness plan as either excellent or adequate. Vaccine hesitancy and concern about adverse reactions were the most common anticipated barriers to COVID-19 vaccination. Only 60% believed currently that COVID-19 vaccination should be mandatory.
This first-in-human trial shows that a subunit vaccine comprising mammalian cell culture-derived, MF59-adjuvanted, molecular clamp-stabilised recombinant spike protein elicits strong immune responses with a promising safety profile. However, the glycoprotein 41 peptide present in the clamp created HIV diagnostic assay interference, a possible barrier to widespread use highlighting the criticality of potential non-spike directed immunogenicity during vaccine development. Studies are ongoing with alternative molecular clamp trimerisation domains to ameliorate this response.
April 17, 2021
Myelopathy associated with SARS-COV-2 infection. A systematic review
Considering the imminent arrival of new vaccines against COVID-19 pandemic, and their potential risk for postvaccination transverse myelitis, this characterization of COVID-19 related myelopathy is of utmost importance.
April 16, 2021
COVID vaccines and blood clots: five key questions
As safety concerns delay the use of two COVID-19 vaccines, Nature looks at the questions that scientists want answered.
Those who tested positive between two weeks after the first dose and one week after the second dose, were disproportionally infected by B.1.1.7 (odds ratio of 26:10), suggesting reduced vaccine effectiveness against both VOCs at particular time windows following vaccination. Nevertheless, the B.1.351 incidence in Israel to-date remains low and vaccine effectiveness remains high among those fully vaccinated. These results overall suggest that vaccine breakthrough infection may be more frequent with both VOCs, yet a combination of mass-vaccination with two doses coupled with non-pharmaceutical interventions control and contain their spread.
ED visits during December 2020–January 2021 were 25% lower than during the same months the year before. Higher proportions of ED patients are seeking care for mental and behavioral health–related concerns, especially pediatric patients.
Estimates of excess deaths, defined as the number of persons who have died from all causes, above the expected number of deaths for a given place and time, can provide a comprehensive account of mortality likely related to the COVID-19 pandemic, including deaths that are both directly and indirectly associated with COVID-19. Since April 2020, CDC’s National Center for Health Statistics (NCHS) has published weekly data on excess deaths associated with the COVID-19 pandemic (1). A previous report identified nearly 300,000 excess deaths during January 26–October 3, 2020, with two thirds directly associated with COVID-19 (2). Using more recent data from the National Vital Statistics System (NVSS), CDC estimated that 545,600–660,200 excess deaths occurred in the United States during January 26, 2020–February 27, 2021.
In late June 2020, the percentage of ED visits for COVID-19 increased and reached a peak of 2.8% of all ED visits in early July before declining through August. This decline was followed by a larger and more prolonged increase beginning in September 2020 that reached a peak (7.2%) in early January 2021. Influenza activity generally begins in October with increased activity throughout the winter months. By the beginning of February 2018, the percentage of ED visits for influenza reached 3.1%, and by the beginning of February 2019, reached 5.0%. During June 2020–March 2021, ED visits for influenza accounted for less than 0.1% of all visits.
Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination
Vaccination against SARS-CoV-2 remains critical for control of the Covid-19 pandemic. A pathogenic PF4-dependent syndrome, unrelated to the use of heparin therapy, can occur after the administration of the ChAdOx1 nCoV-19 vaccine. Rapid identification of this rare syndrome is important because of the therapeutic implications.
SARS-CoV-2 Vaccine–Induced Immune Thrombotic Thrombocytopenia
The coronavirus disease 2019 (Covid-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulated the development of highly effective vaccines that were produced with unprecedented speed with the use of diverse technologies. No major safety warnings, other than rare cases of anaphylaxis, were reported in the initial trials, which involved tens of thousands of adults, and the risk of serious adverse effects has remained remarkably low after vaccination of more than 400 million people worldwide to date.
Thrombotic Thrombocytopenia after Ad26.COV2.S Vaccination — Response from the Manufacturer
A case report by Muir et al.1 describes thrombosis, including cerebral venous sinus thrombosis (CVST), associated with severe thrombocytopenia and disseminated intravascular coagulation in a recipient of the Ad26.COV2.S vaccine (Johnson & Johnson/Janssen) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Indoor Air Changes and Potential Implications for SARS-CoV-2 Transmission
Buildings have been associated with spread of infectious diseases, such as outbreaks of measles, influenza, and Legionella. With SARS-CoV-2, the majority of outbreaks involving 3 or more people have been linked with time spent indoors, and evidence confirms that far-field airborne transmission (defined as within-room but beyond 6 feet) of SARS-CoV-2 is occurring.
Fitted Filtration Efficiency of Double Masking During the COVID-19 Pandemic
Although global vaccination efforts against SARS-CoV-2 are underway, the public is urged to continue using face masks as a primary intervention to control transmission.
April 15, 2021
These data show that the incidence of CVT is significantly increased after COVID-19,andgreater than that observed with BNT162b2 and mRNA-1273 COVID-19 vaccines. The risk of CVT following COVID-19 is also higher than the latest estimate from the European Medicines Agency for the incidence associated withChAdOx1 nCoV-19 vaccine (5.0 per million people, 95% CI 4.3–5.8). Although requiring replication and corroboration, the present data highlight the risk of serious thrombotic events in COVID-19, and can help contextualize the risks and benefits of vaccination in this regard.
BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting
This study in a nationwide mass vaccination setting suggests that the BNT162b2 mRNA vaccine is effective for a wide range of Covid-19–related outcomes, a finding consistent with that of the randomized trial.
We identified two distinct phenotypes of COVID-19-associated ARDS, with substantial differences in biochemical profiles despite minimal differences in respiratory dynamics. The minority phenotype (class 2, n = 70, 26·6%) demonstrated increased markers of coagulopathy, with mild relative hyper-inflammation and dramatically increased markers of end-organ dysfunction (e.g., creatinine, troponin). The odds of 28-day mortality among the class 2 phenotype was more than double that of the class 1 phenotype (40·0% vs.· 23·3%, OR = 2·2, 95% CI [1·2, 3·9]).
Given the known immuno- and neuro-pathogenicity of HERV-W ENV protein, it could promote certain pathogenic features of COVID-19 and therefore serve as a biomarker to predict clinical progression of disease and open to further studies for therapeutic intervention.
Epigenome-wide association study of COVID-19 severity with respiratory failure
We identified DNA methylation sites as epigenetic susceptibility loci for respiratory failure in COVID-19 patients. These candidate biomarkers, combined with other clinical, cellular and genetic factors, could be useful in the clinical stratification and management of patients infected with the SARS-CoV-2.
Vaccines that can protect against many coronaviruses could prevent another pandemic
In 2017, three leading vaccine researchers submitted a grant application with an ambitious goal. At the time, no one had proved a vaccine could stop even a single beta coronavirus—the notorious viral group then known to include the lethal agents of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), as well as several causes of the common cold and many bat viruses. But these researchers wanted to develop a vaccine against them all.
Impact of cancer history on outcomes among hospitalized COVID‐19 patients
Patients with a history of cancer hospitalized for COVID‐19 had similar mortality to matched hospitalized COVID‐19‐positive patients without cancer, and a lower risk of complications. In this population, patients with active cancer or recent cancer treatment had a similar risk for adverse outcomes compared to cancer survivors.
Several rapid antigen tests (RATs) for the detection of SARS-CoV-2 were evaluated recently. However, reliable performance data for laboratory-based, high-throughput antigen tests are lacking. Therefore and in response to a short-term shortage of PCR reagents, we evaluated DiaSorin's LIAISON SARS-CoV-2 antigen test in comparison to RT-qPCR, and concerning the application of screening non-COVID-19 patients on hospital admission.
Holding conspiracy beliefs regarding the coronavirus pandemic in the US has been associated with reductions in both actions to prevent the spread of the infection (e.g., mask wearing) and intentions to accept a vaccine when one becomes available.
Most MS patients included in this study had a favourable course of SARS-CoV-2 infection. The hospitalisation rate and the mortality rate were not higher in the MS cohort compared to the general Polish population. Continued multicentre data collection is needed to increase the understanding of SARS-CoV-2 infection impact on the course of MS in patients treated with DMTs.
Patients on dialysis are at high risk for death due to COVID-19, yet a significant proportion do survive as evidenced by presence of SARS-CoV-2 antibodies in 8% of patients in the U.S. in July 2020. It is unclear whether patients with seropositivity represent the subgroup with robust health status, who would be more likely to mount a durable antibody response.
We presented a machine learning model that could be effectively used as a predictor of adverse outcomes in hospitalized patients with COVID-19, opening up the possibility for patient stratification and treatment allocation.
COVID-19 neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital
Many patients with SARS-CoV-2 infection develop neurological signs and symptoms, though, to date, little evidence exists that primary infection of the brain is a significant contributing factor. We present the clinical, neuropathological, and molecular findings of 41 consecutive patients with SARS-CoV-2 infections who died and underwent autopsy in our medical center.
Recent studies have suggested that, to reach immunity, immunocompetent SARS-CoV-2 seropositive adults may only require 1 dose rather than 2 doses of a messenger RNA vaccine; however, these studies did not include older adults. Older adults living in nursing homes are at higher risk for severe COVID-19, and the immune response to the vaccine may differ from that of younger, healthier adults.
This cross-sectional study analyzed prescriptions from 90 420 353 patients and found that from March 18 to May 19, 2020, total morphine milligram equivalents of opioid analgesics prescribed to existing patients followed prepandemic trends; prescriptions to opioid-naive patients were 34% below projected levels but rebounded by August 2020. Prescribing of buprenorphine for opioid use disorder followed prepandemic trends for existing patients, while prescriptions to new patients were 18% below projected levels, rebounding to 90% of projected levels by August 2020.
Seropositive young adults had about one-fifth the risk of subsequent infection compared with seronegative individuals. Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralisation activity or immunity against subsequent infection. These findings might be relevant for optimisation of mass vaccination strategies.
SARS-CoV-2 reinfection in a closed setting: lessons for the community
In a study published in The Lancet Respiratory Medicine, Andrew Letizia and colleagues analysed the subsequent infection risk for SARS-CoV-2 in healthy young adults with and without previous antispike IgG antibodies. They followed Marine recruits for 6 weeks after a 2-week supervised quarantine period. Serology and PCR tests for SARS-CoV-2 were performed upon arrival to supervised quarantine, and PCR was repeated on weeks 1 and 2 of quarantine, and then every other week (weeks 2, 4, and 6) thereafter.
April 14, 2021
Based on laboratory modeling of exposure to SARS-CoV-2 on single-aisle and twin-aisle aircraft, exposures in scenarios in which the middle seat was vacant were reduced by 23% to 57%, compared with full aircraft occupancy, depending upon the model.
Thrombotic Thrombocytopenia after Ad26.COV2.S Vaccination
Thrombosis and thrombocytopenia have been reported after vaccination with the ChAdOx1 nCoV-19 vaccine (Oxford–AstraZeneca), a recombinant chimpanzee adenoviral vector encoding the spike glycoprotein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
SARS-CoV-2 Antibody Response in Persons with Past Natural Infection
Whether or not persons who have already been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should be vaccinated is unclear. Only a few studies have shown that vaccinees who were previously infected with SARS-CoV-2 had a significantly higher antibody response than previously uninfected vaccinees.
Spatiotemporal pattern of COVID-19 spread in Brazil
Brazil has been severely hit by COVID-19, with rapid spatial spread of both cases and deaths. We use daily data on reported cases and deaths to understand, measure, and compare the spatiotemporal pattern of the spread across municipalities. Indicators of clustering, trajectories, speed, and intensity of the movement of COVID-19 to interior areas, combined with indices of policy measures show that while no single narrative explains the diversity in the spread, an overall failure of implementing prompt, coordinated, and equitable responses in a context of stark local inequalities fueled disease spread. This resulted in high and unequal infection and mortality burdens. With a current surge in cases and deaths and several variants of concern in circulation, failure to mitigate the spread could further aggravate the burden.
After the rising period of the COVID-19 outbreak in mainland China, cognitive and affective variables still played important roles in predicting behavioral responses. Compared with cognitive factors, affective factors demonstrated stronger explanatory power in predicting behavioral responses toward COVID-19. The findings may have implications for enhancing individual compliance with guidelines of adopting preventive behaviors in response to COVID-19.
Two easy-to-use risk stratification score systems were built to predict the outcomes in COVID-19 patients with different clinical types. Identifying high risk patients with longer stay or poor prognosis could assist healthcare providers in triaging patients when allocating limited healthcare during COVID-19 outbreak.
This study has provided a number of recommendations for how hospital pharmacy departments may respond to a global pandemic. These experiences derived from the pharmacy departments at two large UK NHS Trusts may be used by other healthcare providers to help inform the pharmacy response to a global pandemic.
Development and validation of a 3D printed antiviral ventilator filter - a comparative study
Our filter may be of particular importance to those working in low middle-income countries unable to compete with stronger economies. Our design relies on products available outside the healthcare supply chain, much of which can be purchased in grocery stores, hardware stores, or industrial and academic institutions. We hope that these HMEs and viral filters may be beneficial to clinicians who face critical supply chain issues during the COVID-19 pandemic.
April 13, 2021
COVID-19 Presenting as Acute Necrotizing Pancreatitis
The ongoing pandemic of the novel coronavirus disease 2019 (COVID-19) originated in Wuhan, China, in December 2019. Various manifestations of coronavirus (SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2]) have been reported since the pandemic began. Some articles have reported acute pancreatitis in several patients due to COVID-19 infection.
COVID-19 Precautions Are Scarce in Non–Health Care Workplaces
Less than half of US workers in non–health care fields had COVID-19 prevention measures in place at work as of June 2020, based on an online survey of 4000 US, nonremote workers.
April 12, 2021
In this updated interim analysis, inhaled budesonide reduced time to recovery by a median of 3 days in people with COVID-19 with risk factors for adverse outcomes. Once 28 day follow up is complete for all participants randomized to budesonide, final analyses of time to recovery and hospitalization/death will be published.
The COVID-19 pandemic has had negative consequences on HIV care and prevention programs, including routine HIV screening in health care settings.
Rapid Response System Adaptations at 40 US Hospitals During the COVID-19 Pandemic
Most RRSs reported pandemic-related adjustments, most commonly through increasing resources and implementation of protocol changes. There was a reduction in the number of sites that performed simulation training.
Several small studies have suggested that patients with positive test results for COVID-19 infection may experience worse perioperative outcomes and increased mortality after surgery.
Emerging evidence exists of increased transmissibility of B.1.1.7, and we found increased virus load by proxy for B.1.1.7 in our data. We did not identify an association of the variant with severe disease in this hospitalised cohort.
The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant.
Within each U.S. Census region, the proportion of hospitalized patients with COVID-19 was highest for Hispanic or Latino patients. Racial and ethnic disparities were largest during May–July 2020 and became less pronounced as the pandemic spread throughout the country; however, disparities remained in December 2020 in all regions.
Emergency Department Visits for COVID-19 by Race and Ethnicity — 13 States, October–December 2020
Data from 13 states indicate that compared with White persons, Hispanic and American Indian or Alaska Native persons experienced 1.7 times the rate, and Black persons experienced 1.4 times the rate of emergency department care visits for COVID-19 during October–December 2020.
SARS-CoV-2–Specific Antibodies in Breast Milk After COVID-19 Vaccination of Breastfeeding Women
This study found robust secretion of SARS-CoV-2 specific IgA and IgG antibodies in breast milk for 6 weeks after vaccination. IgA secretion was evident as early as 2 weeks after vaccination followed by a spike in IgG after 4 weeks (a week after the second vaccine). A few other studies have shown similar findings in women infected with COVID-19.5 Antibodies found in breast milk of these women showed strong neutralizing effects, suggesting a potential protective effect against infection in the infant.
Epidemiologic studies on the safety of the mRNA-based COVID-19 vaccines in patients with AIIRD are needed to clarify the association between the BNT162b2 mRNA vaccination and reactivation of zoster.
The SARS-CoV-2 lineage B.1.1.7 is characterised by a suite of defining mutations in the immunodominant spike protein, including a signature Asp501Tyr substitution in the receptor-binding domain.
First reported in December 2020, in the UK, the variant's discovery coincided with a substantial surge in case numbers and fatalities in the UK, raising concerns that this variant was both more infectious and virulent than previous variants. Epidemiological and modelling studies have yielded good evidence that B.1.1.7 is more transmissible than other variants.
Monitoring differences between the SARS-CoV-2 B.1.1.7 variant and other lineages
As focus in the SARS-CoV-2 pandemic shifts to the emergence of new variants of concern (VOC), characterising the differences between new variants and non-VOC lineages will become increasingly important for surveillance and maintaining the effectiveness of both public health and vaccination programmes.
April 11, 2021
Social distancing mediated generalized model to predict epidemic spread of COVID-19
The extensive proliferation of recent coronavirus (COVID-19), all over the world, is the outcome of social interactions through massive transportation, gatherings and population growth. To disrupt the widespread of COVID-19, a mechanism for social distancing is indispensable.
April 9, 2021
Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination
Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder.
Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination
We report findings in five patients who presented with venous thrombosis and thrombocytopenia 7 to 10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against coronavirus disease 2019 (Covid-19). The patients were health care workers who were 32 to 54 years of age.
How could a COVID vaccine cause blood clots? Scientists race to investigate
The very rare occurrence of a mysterious blood-clotting disorder among some recipients of the Oxford–AstraZeneca COVID-19 vaccine has got researchers scrambling to uncover whether, and if so, how the inoculation could trigger such an unusual reaction.
Those infected between two weeks after the first dose and one week after the second dose, were disproportionally infected by B.1.1.7 (odds ratio of 26:10), suggesting reduced vaccine effectiveness against both VOCs under different dosage/timing conditions. Nevertheless, the B.1.351 incidence in Israel to-date remains low and vaccine effectiveness remains high against B.1.1.7, among those fully vaccinated. These results overall suggest that vaccine breakthrough infection is more frequent with both VOCs, yet a combination of mass-vaccination with two doses coupled with non-pharmaceutical interventions control and contain their spread.
Public Perspectives on COVID-19 Vaccine Prioritization
In this survey study of 4735 US adults, respondents of all demographic and political affiliations agreed with prioritizing health care workers, adults of any age with serious comorbid conditions, frontline workers (eg, teachers and grocery workers), and Black, Hispanic, Native American, and other communities that have been disproportionately affected by COVID-19. Older adult respondents were less likely than younger respondents to list healthy people older than 65 years as 1 of their top 4 priority groups.
Studies have suggested that sequence variants in the genome of SARS-CoV-2 may affect infectivity, transmission, and pathogenicity of the virus.1-3 In this study, genome analysis was performed on SARS-CoV-2 RNA recovered from 7 individuals in a long-term care facility who were asymptomatic at time of screening.
Our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still developing. We perform an observational study to investigate seroprevalence and immune responses in subjects professionally exposed to SARS-CoV-2 and their family members (155 individuals; ages 5–79 years). Seropositivity for SARS-CoV-2 Spike glycoprotein aligns with PCR results that confirm the previous infection. Anti-Spike IgG/IgM titers remain high 60 days post-infection and do not strongly associate with symptoms, except for fever.
Helping the Public Understand Adverse Events Associated With COVID-19 Vaccinations
By the end of January 2021, more than 97.3 million doses globally and 31.8 million doses in the United States have been administered of the COVID-19 vaccine. Although important postmarketing surveillance is ongoing, it is currently highly effective and safe, with adverse effects including transient symptoms such as fever/chills, headache, fatigue, myalgia/arthralgia, lymphadenopathy, nausea, or local effects of swelling, erythema, or pain.
Among 378,048 death certificates from 2020 listing COVID-19, 5.5% listed COVID-19 without codes for any other conditions. Among 357,133 death certificates with at least one other condition, 97% had a co-occurring diagnosis of a plausible chain-of-event condition (e.g., pneumonia or respiratory failure), or a significant contributing condition (e.g., hypertension or diabetes), or both.
April 8, 2021
A novel variant of SARS-CoV-2, B.1.1.7, originally discovered in the UK, is rapidly overtaking wild-type SARS-CoV-2 globally, due to a substantial transmission advantage. This variant is estimated to be 40% to 80% more transmissible and 35% more lethal3 than the wild-type virus.
Mortality Among US Patients Hospitalized With SARS-CoV-2 Infection in 2020
This cohort study of 503 409 patients from 209 US acute care hospitals found a decrease in in-hospital mortality among patients with SARS-CoV-2–positive tests. Mortality rates were 10.6% in March, increased to 19.7% in April, and decreased to 9.3% in November.
The main objective of this study was to analyse neurological symptoms during a Covid-19 infection and determine the pattern of symptoms by comparing outpatients with inpatients. A further goal was to identify possible predictors, such as pre-existing conditions and neurological symptoms.
April 7, 2021
Symptoms and Functional Impairment Assessed 8 Months After Mild COVID-19 Among Health Care Workers
The results of this study showed that a considerable portion of low-risk individuals with mild COVID-19 reported a diversity of long-term symptoms, and that these symptoms disrupted work, social, and home life. Limitations of the study include the possibility of recall bias and the subjective rating of symptoms. Further research is needed to understand the mechanisms underlying COVID-19–related long-term sequalae.
In this cross-sectional study of 1 088 314 US adults, African American individuals with low income, Hispanic individuals, and women of all racial/ethnic groups had higher risks of experiencing unemployment, class cancellations, food insufficiency, and mental health problems during the first wave of the COVID-19 pandemic.
Antigen point-of-care tests (AgPOCTs) can accelerate SARS-CoV-2 testing. As some AgPOCTs have become available, interest is growing in their utility and performance. Here we aimed to compare the analytical sensitivity and specificity of seven commercially available AgPOCT devices.
The relationship of large city out-of-hospital cardiac arrests and the prevalence of COVID-19
Though variable, many major metropolitan cities reported profound and unprecedented increases in out-of-hospital cardiac arrest (OHCA) in early 2020. This study examined the relative magnitude of those increases and their relationship to COVID-19 prevalence.
Host determinants of severe coronavirus disease 2019 include advanced age, comorbidities and male sex. Virologic factors may also be important in determining clinical outcome and transmission rates, but limited patient-level data is available.
During December 3, 2020–January 31, 2021, CDC, in collaboration with the University of Utah Health and Economic Recovery Outreach Project, Utah Department of Health (UDOH), Salt Lake County Health Department, and one Salt Lake county school district, offered free, in-school, real-time reverse transcription–polymerase chain reaction (RT-PCR) saliva testing as part of a transmission investigation of SARS-CoV-2, the virus that causes COVID-19, in elementary school settings.
April 6, 2021
In this prognostic study of more than 7.6 million individuals enrolled in the Veterans Affairs health care system, a logistic regression model (COVIDVax) was developed to estimate risk of SARS-CoV-2–related death using the following 10 characteristics: sex, age, race, ethnicity, body mass index, Charlson Comorbidity Index, diabetes, chronic kidney disease, congestive heart failure, and the Care Assessment Need score. The model was estimated to save more lives than prioritizing vaccination based on age or on the US Centers for Disease Control and Prevention vaccination allocation.
In this cross-sectional study of 17 235 pediatric patients, the number of admissions for KD showed no significant change (27.4% decrease) during quarantine owing to the COVID-19 pandemic, whereas there were significant decreases in numbers of hospital admissions for droplet-transmitted or contact-transmitted respiratory tract infections (75.3% decrease) and gastrointestinal infections (86.3% decrease). Thus, the ratio of KD admissions to admissions for these infections increased.
Antibody Persistence through 6 Months after the Second Dose of mRNA-1273 Vaccine for Covid-19
Interim results from a phase 3 trial of the Moderna mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine indicated 94% efficacy in preventing coronavirus disease 2019 (Covid-19).1 The durability of protection is currently unknown.
April 5, 2021
Patient Use and Clinical Practice Patterns of Remote Cardiology Clinic Visits in the Era of COVID-19
In this cross-sectional study of 176 781 ambulatory cardiology visits, patients using COVID-era remote visits were more likely to be Asian, Black, or Hispanic individuals, have private insurance, and have cardiovascular comorbidities. Compared with pre-COVID in-person visits, clinicians during COVID-era video and telephone visits had a significantly lower odds of ordering any medication as well as most tests.
The observed variability in susceptibility to SARS-CoV-2 and severity of the ensuing COVID-19 have raised intense interest in their environmental and genetic risk factors. An early report from China suggested that blood group A was associated with increased susceptibility and blood group O was associated with reduced susceptibility to SARS-CoV-2 infection.
Forty-six cases of COVID-19 were linked to an indoor bar opening event that occurred during February 2021 in a rural Illinois county. Event patrons were linked to secondary cases among household, long-term care facility, and school contacts, resulting in one hospitalization and one school closure affecting 650 students.
April 3, 2021
The frequency of SARS-CoV-2 infections in preschool and school children is an important parameter for decisions regarding kindergarten and school openings and procedures. Evidence indicates that children have lower susceptibility to SARS-CoV-2 infection than adults, but data in children from the general population are relatively few (Viner et al., 2021).
April 2, 2021
Prospective cohorts of 3,950 health care personnel, first responders, and other essential and frontline workers completed weekly SARS-CoV-2 testing for 13 consecutive weeks. Under real-world conditions, mRNA vaccine effectiveness of full immunization (≥14 days after second dose) was 90% against SARS-CoV-2 infections regardless of symptom status; vaccine effectiveness of partial immunization (≥14 days after first dose but before second dose) was 80%.
April 1, 2021
The spread of SARS-CoV-2 created a pandemic crisis with > 150,000 cumulative cases in > 65 countries within a few months. The reproductive number (R) is a metric to estimate the transmission of a pathogen during an outbreak. Preliminary published estimates were based on the initial outbreak in China.
Risk for International Importations of Variant SARS-CoV-2 Originating in the United Kingdom
The United Kingdom has detected a variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent coronavirus disease (COVID-19), from samples initially collected in Kent on September 20 and London on September 21, 2020. The variant was associated with increased transmissibility and includes deletions at amino acid sites 69 and 70 of the spike protein. In mid-December, the UK government tightened measures in London and southeastern England to mitigate transmission of the fast-spreading virus variant.
Can technology increase COVID-19 vaccination rates?
Vaccine ready is the theme of the National Minority Health Month in April, 2021. This initiative aims to educate the public on health problems facing minority populations in the USA. The vaccine theme has been chosen because, paradoxically, although minority populations have been disproportionately impacted by COVID-19, they are also reported to be the least likely to be vaccinated. Barriers against vaccination among minority populations have been widely reported, including low confidence in the vaccine, poor access, and distrust of the health system.
March 31, 2021
Provisional Mortality Data — United States, 2020
The age-adjusted death rate increased by 15.9% in 2020. Overall death rates were highest among non-Hispanic Black persons and non-Hispanic American Indian or Alaska Native persons. COVID-19 was the third leading cause of death, and the COVID-19 death rate was highest among Hispanics.
Among 378,048 death certificates from 2020 listing COVID-19, 5.5% listed COVID-19 without codes for any other conditions. Among 357,133 death certificates with at least one other condition, 97% had a co-occurring diagnosis of a plausible chain-of-event condition (e.g., pneumonia or respiratory failure), or a significant contributing condition (e.g., hypertension or diabetes), or both.
The Leading Causes of Death in the US for 2020
Vital statistics data provide the most complete assessment of annual mortality burden and contribute key measurements of the direct and indirect mortality burden during a public health pandemic. While mortality statistics have historically been produced annually, the COVID-19 pandemic introduced a pressing need for the National Center for Health Statistics (NCHS) National Vital Statistics System (NVSS) to rapidly release reliable provisional mortality data. Provisional estimates indicate a 17.7% increase in the number of deaths in 2020 (the increase in the age-adjusted rate was 15.9%) compared with 2019, with increases in many leading causes of death.
The study’s findings suggest that ACEIs and ARBs may be associated with protective benefits for patients with COVID-19 and that patients may continue receiving ACEIs and ARBs for the treatment of any condition without an increased risk of worse outcomes unless specifically advised to avoid them by treating clinicians.
In this cohort study among 482 323 long-stay residents, risk of SARS-CoV-2 infections were associated with geographic area and the specific facility, not by characteristics of the residents. Among residents diagnosed with SARS-CoV-2 infections, the risk of hospitalization associated with individual resident characteristics differed from the risk of death.
In this decision analytical modelling study of a synthetic population of 1 000 000 individuals in Ontario, Canada, compared with community-based nonpharmaceutical interventions, school closure was associated with a small change in estimated COVID-19 incidence trajectories and cumulative case counts.
In this survey study of 6084 US adults, those with 7 of 9 medical risk factors for COVID-19 complications reported higher perceived chance of hospitalization or death from COVID-19 if infected compared with those without the factor. While nearly all adults reported recent mask wearing, during several common activities the majority, including susceptible adults, did not consistently wear masks.
The devastation of the Covid-19 pandemic has been rippling through Black, Indigenous, and People of Color (BIPOC) communities throughout the United States. The Centers for Disease Control and Prevention has reported horrifyingly disproportionate age-adjusted rates of cases, hospitalizations, and deaths. Black Americans have had hospitalization and death rates 9 times as high as those for White Americans; American Indians and Alaska Natives have seen 9 times as many cases and 4 times as many deaths as White Americans; and Latinx/Hispanic Americans have faced 3 times as many deaths as their White counterparts.
“Vaccine Passport” Certification — Policy and Ethical Considerations
As the Covid-19 pandemic enters its next phase, fervent desires to return to normalcy coupled with the rollout of efficacious vaccines have intensified discussions of “vaccine passports” — certifications of vaccination that reduce public health restrictions for their bearers.
Scaling Up Covid-19 Vaccination in Africa — Lessons from the HIV Pandemic
Concerns regarding access to Covid-19 vaccines in Africa are reminiscent of concerns raised about responding to the HIV pandemic in the mid-1990s and early 2000s, when highly active antiretroviral treatment (ART) was accessible in high-income countries but had limited availability in African countries — a disparity that resulted in many preventable deaths in these high-burden settings.
March 30, 2021
Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial
A new variant of SARS-CoV-2, B.1.1.7, emerged as the dominant cause of COVID-19 disease in the UK from November, 2020. We report a post-hoc analysis of the efficacy of the adenoviral vector vaccine, ChAdOx1 nCoV-19 (AZD1222), against this variant.
In patients with type 2 diabetes, hyperglycaemia is an independent risk factor for COVID-19-related mortality. Associations between pre-infection prescription for glucose-lowering drugs and COVID-19-related mortality in people with type 2 diabetes have been postulated but only investigated in small studies and limited to a few agents. We investigated whether there are associations between prescription of different classes of glucose-lowering drugs and risk of COVID-19-related mortality in people with type 2 diabetes.
A qualitative study of bereaved relatives’ end of life experiences during the COVID-19 pandemic
Health and social care professionals can have an important role in mitigating the absence of relatives’ visits at end of life during a pandemic. Strategies include prioritising virtual connectedness and creating alternative opportunities for relatives to ‘say goodbye’.
This study examined whether CD8+ T-cell responses from COVID-19 convalescent individuals (n=30) potentially maintain recognition of the major SARS-CoV-2 variants (n=45 mutations assessed). Only one mutation found in B.1.351-Spike overlapped with a previously identified epitope (1/52), suggesting that virtually all anti-SARS-CoV-2 CD8+ T-cell responses should recognize these newly described variants.
Researchers reveal SARS-CoV-2 distribution and relation to tissue damage in patients
Researchers have mapped the distribution of SARS-CoV-2, the virus that causes COVID-19, in deceased patients with the disease, and shed new light on how viral load relates to tissue damage.
Surveys have demonstrated racial differences in the public’s willingness to receive a COVID-19 vaccine but have not directly compared vaccine intentions among health workers and the general public. We investigated COVID-19 vaccine intentions among racially and ethnically diverse samples of health workers and the general population.
March 29, 2021
Since its emergence in December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread globally and become a major public health burden. Despite its close phylogenetic relationship to SARS-CoV, SARS-CoV-2 exhibits increased human-to-human transmission dynamics, likely due to efficient early replication in the upper respiratory epithelium of infected individuals.
In this comparative effectiveness study reanalyzing data from 8 randomized trials across oncology, radiation fractionation was not associated with outcomes in low COVID-19–risk scenarios. In higher-risk scenarios, aggressive hypofractionation was associated with a survival benefit, whereas moderate hypofractionation was not.
Prospective cohorts of 3,950 health care personnel, first responders, and other essential and frontline workers completed weekly SARS-CoV-2 testing for 13 consecutive weeks. Under real-world conditions, mRNA vaccine effectiveness of full immunization (≥14 days after second dose) was 90% against SARS-CoV-2 infections regardless of symptom status; vaccine effectiveness of partial immunization (≥14 days after first dose but before second dose) was 80%.
March 26, 2021
During August 2020–February 2021, the percentage of adults with recent symptoms of an anxiety or a depressive disorder increased from 36.4% to 41.5%, and the percentage of those reporting an unmet mental health care need increased from 9.2% to 11.7%. Increases were largest among adults aged 18–29 years and those with less than a high school education.
March 25, 2021
COVID-19 vaccine response in pregnant and lactating women: a cohort study
COVID-19 mRNA vaccines generated robust humoral immunity in pregnant and lactating women, with immunogenicity and reactogenicity similar to that observed in non-pregnant women. Vaccine-induced immune responses were significantly greater than the response to natural infection. Immune transfer to neonates occurred via placenta and breastmilk.
In this randomized trial that included 109 patients, the median number of days free of respiratory support within 28 days was 20 days in the group that received helmet noninvasive ventilation and 18 days in the group that received high-flow nasal oxygen, a difference that was not statistically significant.
Respiratory Support During the COVID-19 PandemicIs It Time to Consider Using a Helmet?
Acute hypoxemic respiratory failure (AHRF) is the most common organ failure and cause of admission to the intensive care unit (ICU) among patients with COVID-19. As with all forms of AHRF, ICU management is supportive while treating the underlying cause. Because the traditional respiratory support of invasive ventilation, ie, intubation and coupling of the patient to the mechanical ventilator, carries high morbidity and mortality, less invasive respiratory support methods have been studied for decades. The overwhelming demands on ICU resources seen during waves of the SARS-CoV-2 pandemic have accelerated interest in the applicability of alternative respiratory support.
Rapid diagnostic tests had good overall sensitivity for diagnosing SARS-CoV-2 infection. Rapid diagnostic tests could be incorporated into efficient testing algorithms as an alternative to PCR to decrease diagnostic delays and onward viral transmission.
Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases.
COVID-19: A retrospective by the numbers
Since January of last year, the medical and public health worlds have been transfixed by the SARS-CoV2 virus and the COVID-19 pandemic it generated. This all-consuming focus on the medical, public health and socio-economic impacts of the pandemic has resulted in a plethora of scientific articles submitted to medical and public health publications and by December 2020 the number of new manuscripts approached 200, 000 by one estimate.
March 24, 2021
Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States
The highly transmissible B.1.1.7 variant of SARS-CoV-2, first identified in the United Kingdom, has gained a foothold across the world. Using S gene target failure (SGTF) and SARS-CoV-2 genomic sequencing, we investigated the prevalence and dynamics of this variant in the United States (U.S.), tracking it back to its early emergence.
During April 1–14, 11.4% of counties reported high COVID-19 incidence, including 28.7% and 27.9% of counties with large Asian and Black populations, respectively. During August 5–18, this percentage was 64.7%, including 92.4% and 74.5% of counties with large Black and Hispanic populations, respectively. By December 9–22, 99.1% of counties reported high incidence.
To address future waves of the pandemic, health authorities should thus focus on facilitating self‐efficacy in the public.
TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation.
The ongoing pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 63 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective 64 studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory 65 factors are associated with both increased disease severity and mortality. Here, using 66 multidimensional epigenetic, transcriptional, in vitro and in vivo analyses, we report that 67 Topoisomerase 1 (TOP1) inhibition suppresses lethal inflammation induced by SARS-68 CoV-2.
March 23, 2021
SARS-CoV-2 Infection after Vaccination in Health Care Workers in California
Data from phase 3 clinical trials of messenger RNA (mRNA) vaccines through November 2020 showed 94.1% efficacy for the prevention of symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at 14 days after the second dose of the mRNA-1273 vaccine (Moderna) and 95% efficacy at 7 days after the second dose of the BNT162b2 vaccine (Pfizer).
March 19, 2021
COVID-19 school-related disease incidence among Florida students was correlated with community incidence in the counties observed and was highest in smaller counties, districts without mask requirements, and those that reopened earliest after closure in March 2020. Incidence increased with the proportion of students receiving in-person instruction. Fewer than 1% of registered students were identified as having school-related COVID-19.
SARS-CoV-2 testing was offered to 1,041 school contacts of 51 index patients across 20 elementary schools in Salt Lake County, Utah. In a high community transmission setting, low school-associated transmission was observed with a 0.7% secondary attack rate. Mask adherence was high, but students’ classroom seats were <6 ft apart and a median of 3 ft apart.
In 22 participating K–12 schools implementing multiple COVID-19 mitigation strategies, school-based SARS-CoV-2 secondary transmission was detected in two of 102 tested close contacts of 37 persons with COVID-19. Among 21 tested student contacts participating in a modified quarantine, all SARS-CoV-2 test results were negative.
In a probability-based survey of parents of children aged 5–12 years, 45.7% reported that their children received virtual instruction only, 30.9% in-person only, and 23.4% combined virtual and in-person instruction. Findings suggest that virtual instruction might present more risks than does in-person instruction related to child and parental mental and emotional health and some health-supporting behaviors.
Frequent facility-wide SARS-CoV-2 testing in a high school with both residential and commuter students was part of a comprehensive strategy, including universal masking, that reduced in-school SARS-CoV-2 transmission while allowing significant daily on- and off-campus movement. Of 19 cases among faculty and staff members and eight among students, two (7%) were considered to represent on-campus transmission.
March 18, 2021
In this randomized clinical trial that included 562 patients with COVID-19 admitted to the ICU, the primary outcome (a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days) occurred in 45.7% of patients in the intermediate-dose prophylactic anticoagulation group and 44.1% of patients in the standard-dose prophylactic anticoagulation group, a difference that was not statistically significant (odds ratio, 1.06).
March 17, 2021
In the first 2.5 months of the U.S. vaccination program, high social vulnerability counties had lower COVID-19 vaccination coverage than did low social vulnerability counties. Although vaccination coverage estimates by county-level social vulnerability varied widely among states, disparities in vaccination coverage were observed in the majority of states.
This cross-sectional study found that racial/ethnic disparities in very preterm birth and preterm birth among 8026 women were similar during the first wave of the COVID-19 pandemic in New York City compared with the same period the year prior.
Four-Month Clinical Status of a Cohort of Patients After Hospitalization for COVID-19
Four months after hospitalization, in an uncontrolled cohort study of 478 survivors of COVID-19, at least 1 new-onset symptom was reported by telephone interview by 244 patients (51%), including fatigue in 134 of 431 (31%), cognitive symptoms in 86 of 416 (21%), and dyspnea in 78 of 478 (16%). Computed tomographic lung scan abnormalities were reported in 63% of 171 patients assessed at an ambulatory visit, mainly subtle ground-glass opacities. Fibrotic lesions were observed in 19% of these 171 patients.
March 16, 2021
Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant
A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant.
March 15, 2021
Among persons who received a first dose and for whom sufficient time had elapsed to receive the second dose, 88.0% had completed the series; 8.6% had not received the second dose but were still within the allowable interval to receive it. Among all 2-dose recipients, 95.6% received the second dose within the recommended interval. Differences in missed doses or second doses administered outside the recommended interval were identified among jurisdictions and demographic groups.
A retrospective cohort analysis in two Connecticut SNFs found partial vaccination with Pfizer-BioNTech COVID-19 vaccine (from >14 days after dose 1 through 7 days after dose 2) to be 63% (95% confidence interval = 33%–79%) effective against SARS-CoV-2 infection.
In this study of immunogenicity of the first dose of the mRNA SARS-CoV-2 vaccine among solid organ transplant recipients, the majority of participants did not mount appreciable antispike antibody responses. However, younger participants, those not receiving anti–metabolite maintenance immunosuppression, and those who received mRNA-1273 were more likely to develop antibody responses. These results contrast with the robust early immunogenicity observed in mRNA vaccine trials, including 100% antispike seroconversion by day 15 following vaccination with mRNA-12735 and by day 21 following vaccination with BNT162b2.
Incentivizing Vaccination Uptake
Vaccine hesitancy, identified in 2019 by the World Health Organization as one of the major threats to global health, has become a potentially more important issue during the COVID-19 pandemic. After a year of worldwide morbidity, mortality, social distancing, and lockdowns, and despite the development of several clinically tested and efficacious vaccines, not everyone is willing to be vaccinated. In light of the devastating health, economic, and social effects of the pandemic, the availability of effective vaccines represents an important component of the hope to return society to normalcy.
March 11, 2021
Immunogenicity of the Ad26.COV2.S Vaccine for COVID-19
This randomized, double-blind, placebo-controlled phase 1 clinical trial of Ad26.COV2.S enrolled 25 participants. Antibodies were detected in vaccine recipients by day 8 and were observed in all vaccine recipients by day 57 after a single immunization. T-cell responses were also generated in vaccine recipients.
Experiences of Latinx Individuals Hospitalized for COVID-19
In this qualitative study of 60 Latinx adults, participants reported COVID-19 misinformation, felt COVID-19 compounded existing social disadvantage, and risked infection because of the need to work. Participants hesitated to seek hospital care because of immigration and economic concerns.
This cross-sectional study, including 6003 participants wearing face masks in public places, found that face mask airtightness was commonly suboptimal, mostly secondary to gaps at the upper face mask edge. Using simple and tolerable approach of sealing the upper face mask edge with an adhesive tape was associated with significant improvement of face mask airtightness.
March 10, 2021
Racial and ethnic disparities in COVID-19 incidence among persons aged <25 years in 16 U.S. jurisdictions evolved during the pandemic. Disparities were substantial during January–April and generally decreased during May–December, largely because of a greater increase in incidence among White persons, rather than a decline among racial and ethnic minority groups. The largest persistent disparities involved Native Hawaiian and Pacific Islander, American Indian or Alaska Native, and Hispanic persons.
March 9, 2021
To minimize transmission of coronavirus disease 2019 (COVID-19), most US states in spring 2020 passed policies promoting social distancing through stay-at-home orders prohibiting nonessential travel.1 While vehicle miles traveled in the US decreased by 41% in April 2020 compared with 2019,2 the effect of this mobility decrease on motor vehicle crashes (MVCs) is poorly understood. We estimated associations between COVID-19–related social distancing policies, traffic volume, and MVC-related outcomes in Ohio.
March 8, 2021
Acute Allergic Reactions to mRNA COVID-19 Vaccines
Anaphylaxis to the mRNA COVID-19 vaccines is currently estimated to occur in 2.5 to 11.1 cases per million doses, largely in individuals with a history of allergy.1 Allergic concerns contribute to vaccine hesitancy; we investigated acute allergic reaction incidence after more than 60 000 mRNA COVID-19 vaccine administrations.
March 5, 2021
Why You Should Not Use Ivermectin to Treat or Prevent COVID-19
FDA has not approved ivermectin for use in treating or preventing COVID-19 in humans. Ivermectin tablets are approved at very specific doses for some parasitic worms, and there are topical (on the skin) formulations for head lice and skin conditions like rosacea. Ivermectin is not an anti-viral (a drug for treating viruses).
Mandating masks was associated with a decrease in daily COVID-19 case and death growth rates within 20 days of implementation. Allowing on-premises restaurant dining was associated with an increase in daily COVID-19 case growth rates 41–100 days after implementation and an increase in daily death growth rates 61–100 days after implementation.
Estimated SARS-CoV-2 Seroprevalence Among Persons Aged <18 Years — Mississippi, May–September 2020
Serologic testing of residual blood specimens collected during May–September 2020, from 1,603 persons aged <18 years suggested that approximately 113,842 (16.3%) of 698,420 young persons in Mississippi might have been infected with SARS-CoV-2 by mid-September 2020, and only 8,993 confirmed and probable COVID-19 cases among young persons had been reported to the Mississippi State Department of Health by August 31.
The possibility of secondary atomization of high-momentum cough droplets by hydrodynamic focusing and extrusion through the microscale pores in the fibrous network of the single/double-layer mask material needs to be considered in determining mask efficacy. Three-layer masks can effectively block these droplets and thus could be ubiquitously used as a key tool against COVID-19 or similar respiratory diseases.
The Future of Health Policy in a Partisan United States
Using recent probability-based national polls, with sample sizes ranging between 1007 and 15 590, this Viewpoint describes the views on 4 issues among those who identify with the majority and minority parties.
March 4, 2021
Many highly neutralizing mAbs engaging the receptor-binding domain or N-terminal domain and most convalescent sera and mRNA vaccine-induced immune sera showed reduced inhibitory activity against viruses containing an E484K spike mutation. As antibodies binding to spike receptor-binding domain and N-terminal domain demonstrate diminished neutralization potency in vitro against some emerging variants, updated mAb cocktails targeting highly conserved regions, enhancement of mAb potency or adjustments to the spike sequences of vaccines may be needed to prevent loss of protection in vivo.
Our findings do not justify the routine use of azithromycin for reducing time to recovery or risk of hospitalisation for people with suspected COVID-19 in the community. These findings have important antibiotic stewardship implications during this pandemic, as inappropriate use of antibiotics leads to increased antimicrobial resistance, and there is evidence that azithromycin use increased during the pandemic in the UK.
Interferon antagonism by SARS-CoV-2: a functional study using reverse genetics
SARS-CoV-2 ORF6 interferes less efficiently with human interferon induction and interferon signalling than SARS-CoV ORF6. Because of the homology of the genes, onward selection for fitness could involve functional optimisation of interferon antagonism. Charged amino acids at positions 51 and 56 in ORF6 should be monitored for potential adaptive changes.
Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19
The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand effects on other clinically relevant outcomes.
March 3, 2021
First Identified Cases of SARS-CoV-2 Variant P.1 in the United States — Minnesota, January 2021
Since December 2020, the Minnesota Department of Health (MDH) Public Health Laboratory has been receiving 100 specimens per week (50 from each of two clinical partners) with low cycle threshold (Ct) values for routine surveillance for SARS-CoV-2, the virus that causes COVID-19. On January 25, 2021, MDH identified the SARS-CoV-2 variant P.1 in one specimen through this surveillance system using whole genome sequencing, representing the first identified case of this variant in the United States.
In December 2020, the B.1.1.7 genetic variant of SARS-CoV-2, the virus that causes COVID-19, was first reported after emergence and rapid circulation in the United Kingdom (1). Evidence suggests that the B.1.1.7 variant is more efficiently transmitted than are other SARS-CoV-2 variants, and widespread circulation could thereby increase SARS-CoV-2 infection and hospitalization rates (1,2). The first reported SARS-CoV-2 B.1.1.7 variant case in the United States was confirmed by sequencing in Colorado on December 29, 2020.
Delayed Large Local Reactions to mRNA-1273 Vaccine against SARS-CoV-2
Baden et al. report on a phase 3 clinical trial of the mRNA-1273 vaccine against SARS-CoV-2, and they provide information on immediate injection-site reactions, which were observed in 84.2% of the participants after the first dose. The trial also showed that delayed injection-site reactions (defined in that trial as those with an onset on or after day 8) occurred in 244 of the 30,420 participants (0.8%) after the first dose and in 68 participants (0.2%) after the second dose.
The Potential Future of the COVID-19 Pandemic
Will SARS-CoV-2 Become a Recurrent Seasonal Infection?
There is growing optimism and hope that by virtue of ongoing immunization efforts, seasonality (declining infections through August), and naturally acquired immunity, by spring and early summer 2021 in the US there will be a substantial decline in the number of deaths and hospitalizations related to COVID-19. However, this optimism must be tempered by several important factors.
Filtering Facepiece Respirator (N95 Respirator) ReprocessingA Systematic Review
Five decontamination processes and 42 studies were reviewed. Ultraviolet germicidal irradiation, moist heat, and microwave-generated steam processing were effective for pathogen removal, preserved respirator filtration, and had short treatment times and readily available equipment. Vaporized hydrogen peroxide is a suitable alternative with longer decontamination durations and is more expensive. Ethylene oxide may leave toxic residues and is less easily implemented.
Our results suggest that SARS-CoV-2 can use TMPRSS2 and closely related proteases for spread in the upper respiratory tract and that spread in the human lung can be blocked by Camostat mesylate and its metabolite GBPA.
Frequent and Persistent Salivary Gland Ectasia and Oral Disease After COVID-19
Overall, this retrospective and prospective cohort study of COVID-19 survivors revealed that residual damage of the oral cavity persists in the vast majority of patients far beyond clinical recovery, and suggests that the oral cavity represents a preferential target for SARS-CoV-2 infection. Further studies are needed to clarify the connection between SARS-CoV-2 infection and oral disorders.
March 2, 2021
On February 28, 2021, after a transparent evidence-based review of all available data, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for use of the Janssen COVID-19 vaccine in persons aged ≥18 years for the prevention of COVID-19.
Predicting the clinical trajectory of individual patients hospitalized with coronavirus disease 2019 (COVID-19) is challenging but necessary to inform clinical care.
Retail Alcohol and Tobacco Sales During COVID-19
Stress during the coronavirus disease 2019 (COVID-19) pandemic may increase substance use.
Alcohol Sales and Alcohol-Related Emergencies During the COVID-19 Pandemic
During the coronavirus disease 2019 (COVID-19) pandemic, many regions across the world recommended stay-at-home orders, closure of public spaces, and physical distancing to reduce community transmission.
March 1, 2021
What Contributes to COVID-19 Vaccine Hesitancy in Black Communities, and How Can It Be Addressed?
Recent polls show that Black Americans are less willing than Americans of other races or ethnicities to be vaccinated for COVID-19. These lower vaccination rates among Black Americans would further widen COVID-19 inequities in diagnosis, hospitalization, and mortality.
Current shortages in COVID-19 vaccine production and distribution have led some experts to suggest untested regimens. Persons who have had COVID-19 are thought to have protective immunity and memory responses for at least 6 months; however, neither recall responses nor ideal vaccine dosing regimens have been studied in those previously infected with SARS-CoV-2.
Comparing the collated cytokine responses caused by the analyzed viruses highlights a SARS-CoV-2-specific dysregulation of the type-I interferon (IFN) response and its downstream cytokine signatures. The map of responses gathered in this study could help specialists identify interventions that alleviate CRS in different diseases and evaluate whether they could be used in the COVID-19 cases.
The Johnson & Johnson Vaccine for COVID-19
Johnson & Johnson has developed a vaccine that works differently than the Pfizer and Moderna vaccines and is highly effective for preventing moderate to severe COVID-19.
Want to track pandemic variants faster? Fix the bioinformatics bottleneck
Tools, rules and incentives are buckling under the flood of coronavirus genome sequences — to help control the pandemic, researchers need new approaches.
COVID-19 outbreaks in aged care facilities (ACFs) often have devastating consequences. However, epidemiologically these outbreaks are not well defined. We aimed to define such outbreaks in ACFs by systematically reviewing literature published during the current COVID-19 pandemic.
February 26, 2021
By February 2021, 2-dose vaccination coverage was 84% among persons aged ≥70 years and 10% among those aged <50 years. The ratio of COVID-19 patients aged ≥70 years requiring mechanical ventilation to those aged <50 years declined 67% from October–December 2020 to February 2021.
Shortly after SARS-CoV emerged at the turn of the 21st century, the spike (S) protein (particularly in its prefusion [native] conformation) was identified as the immunodominant antigen of the virus.
Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With COVID-19
In a meta-analysis of 4 peer-reviewed and published randomized clinical trials including 1060 patients with COVID-19 treated with convalescent plasma vs control, the risk ratio for mortality was 0.93 and after the addition of 6 unpublished randomized clinical trials and 10 722 patients, the risk ratio for mortality was 1.02; neither finding was statistically significant. No significant associations with benefit were shown for hospital length of stay, mechanical ventilation use, clinical improvement, or clinical deterioration.
February 25, 2021
Dexamethasone in Hospitalized Patients with Covid-19
In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support.
Research in the Context of a Pandemic
The current literature on the treatment of coronavirus disease 2019 (Covid-19) is filled with anecdotal reports of therapeutic successes in clinical trials with small numbers of patients and observational cohort studies claiming efficacy with little regard to the effect of unrecognized confounders.
Last-Mile Logistics of Covid Vaccination — The Role of Health Care Organizations
The development, evaluation, and production of vaccines for Covid-19 was the remarkable success story of 2020; the challenge for 2021 is getting those vaccines into the bodies of a critical mass of the world’s population.
Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19
The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.
Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia
Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials.
Interleukin-6 Receptor Inhibition in Covid-19 — Cooling the Inflammatory Soup
Viruses cannot replicate by themselves. Instead, they rely on the host for almost all their replicative functions. Similarly, many viruses are unable to cause damage without the host immune system. Because of this, two strategies can often ameliorate disease — antivirals, which block replication, and antiinflammatories, which can limit the damage induced by infection. In the lung, this latter strategy is exemplified by the treatment of Pneumocystis jiroveci, in which treatment with glucocorticoids reduces the severity of disease and the risk of death.
February 24, 2021
COVID-19 Outbreak Among Attendees of an Exercise Facility — Chicago, Illinois, August–September 2020
In August 2020, 55 COVID-19 cases were identified among 81 attendees of indoor high-intensity classes at a Chicago exercise facility. Twenty-two (40%) persons with COVID-19 attended on or after the day symptoms began. Most attendees (76%) wore masks infrequently, including persons with (84%) and without COVID-19 (60%).
Community Transmission of SARS-CoV-2 at Three Fitness Facilities — Hawaii, June–July 2020
Twenty-one COVID-19 cases were linked to an index case in a fitness instructor, who, along with a patient who was also an instructor, taught classes <1 day, 1 to <2 days, and ≥2 days before symptom onset; aggregate attack rates were 95%, 13%, and 0%, respectively.
BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting
This study in a nationwide mass vaccination setting suggests that the BNT162b2 mRNA vaccine is effective for a wide range of Covid-19–related outcomes, a finding consistent with that of the randomized trial.
In this case series that included 539 patients with MIS-C and 577 patients with severe COVID-19, patients with MIS-C were more likely than those with severe COVID-19 to be 6 to 12 years old, be non-Hispanic Black, and have severe cardiovascular or mucocutaneous involvement and more extreme inflammation.
Growing evidence that pregnant individuals are more likely to experience COVID-19 complications than nonpregnant individuals includes these 3 studies reported in late January:
February 23, 2021
This lineage appeared in late November 2020, and isolates from this lineage account for ~25% of coronavirus genomes sequenced and deposited from New York during February 2021.
Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated.
February 22, 2021
An investigation of SARS-CoV-2 transmission in a Georgia school district during December 1, 2020–January 22, 2021, identified nine clusters of COVID-19 cases involving 13 educators and 32 students at six elementary schools. Two clusters involved probable educator-to-educator transmission that was followed by educator-to-student transmission in classrooms and resulted in approximately one half (15 of 31) of school-associated cases.
Identifying COVID-19 Risk Through Observational Studies to Inform Control Measures
A year into the coronavirus disease 2019 (COVID-19) pandemic there remains an urgent need to limit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread and to curb the pandemic in the US through nonpharmaceutical interventions. Clear evidence supports the effectiveness of simple strategies in identifying risks and mitigating the spread of infection, with much of this evidence coming from observational studies.
Leading signs/symptoms of COVID-19 and risk factors for severe disease course are similar to the general population. However, individuals with DS present significantly higher rates of medical complications and mortality, especially from age 40.
February 19, 2021
Sequelae in Adults at 6 Months After COVID-19 Infection
A total of 177 of 234 participants (75.6%; mean [range] age, 48.0 [18-94] years; 101 [57.1%] women) with COVID-19 completed the survey. Overall, 11 (6.2%) were asymptomatic, 150 (84.7%) were outpatients with mild illness, and 16 (9.0%) had moderate or severe disease requiring hospitalization (Table). Hypertension was the most common comorbidity (23 [13.0%]). The follow-up survey was completed a median (range) of 169 (31-300) days after illness onset among participants with COVID-19 (Figure, A) and 87 (71-144) days after enrollment among 21 patients in the control group. Among participants with COVID-19, persistent symptoms were reported by 17 of 64 patients (26.6%) aged 18 to 39 years, 25 of 83 patients (30.1%) aged 40 to 64 years, and 13 of 30 patients (43.3%) aged 65 years and older.
The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose.
SARS-CoV-2 Positivity on or After 9 Days Among Quarantined Student Contacts of Confirmed Cases
Schools reopened during the fall of 2020 with various approaches to mitigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. At that time, the US Centers for Disease Control and Prevention (CDC) recommended a 14-day quarantine without testing for close contacts of anyone diagnosed with coronavirus disease 2019 (COVID-19).
February 18, 2021
There were substantial reductions in primary care contacts for acute physical and mental conditions following the introduction of restrictions, with limited recovery by July, 2020. Further research is needed to ascertain whether these reductions reflect changes in disease frequency or missed opportunities for care. Maintaining health-care access should be a key priority in future public health planning, including further restrictions. The conditions we studied are sufficiently severe that any unmet need will have substantial ramifications for the people with the conditions as well as health-care provision.
February 17, 2021
Neutralizing Activity of BNT162b2-Elicited Serum — Preliminary Report
BNT162b2 is a nucleoside-modified RNA vaccine expressing the full-length prefusion spike glycoprotein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In a randomized, placebo-controlled clinical trial involving approximately 44,000 participants, immunization conferred 95% efficacy against coronavirus disease 2019 (Covid-19).
SARS-CoV-2 Variants of Concern in the United States—Challenges and Opportunities
On January 10, 2020, the first genomic sequence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from a patient in Wuhan, China, was posted online. As of February 3, 2021, 468 000 sequences of SARS-CoV-2 from COVID-19 cases globally have been uploaded into publicly available databases, including more than 93 000 from individuals in the US. SARS-CoV-2, like other RNA viruses, constantly changes through mutation, with new variants occurring over time.
First Identified Cases of SARS-CoV-2 Variant B.1.1.7 in Minnesota — December 2020–January 2021
On January 9, 2021, the Minnesota Department of Health (MDH) announced the identification of the SARS-CoV-2 variant of concern (VOC) B.1.1.7, also referred to as 20I/501Y.V1 and VOC 202012/01, in specimens from five persons; on January 25, MDH announced the identification of this variant in specimens from three additional persons.
The study does not support the use of a high dose of vitamin D3 for treatment of moderate to severe COVID-19 in hospitalized patients.
February 16, 2021
COVID vaccines and safety: what the research says
It is clear that coronavirus vaccines are safe and effective, but as more are rolled out, researchers are learning about the extent and nature of side effects.
All patients had nodules in the macular region, 8/9 (89%) had bilateral nodules, 2/9 (22%) had nodules outside the macular region. Screening of these patients might improve the management of potentially severe ophthalmological manifestations of the virus.
February 12, 2021
In December 2020, the US Food and Drug Administration (FDA) issued Emergency Use Authorizations for 2 mRNA-based vaccines for prevention of coronavirus disease 2019 (COVID-19): Pfizer-BioNTech COVID-19 vaccine (EUA issued December 11; 2 doses, 3 weeks apart) and Moderna COVID-19 vaccine (EUA issued December 18; 2 doses, 1 month apart). Shortly after each authorization, the Advisory Committee on Immunization Practices issued interim recommendations for use.
February 11, 2021
Emergence of a Novel SARS-CoV-2 Variant in Southern California
A spike in coronavirus disease 2019 (COVID-19) has occurred in Southern California since October 2020. Analysis of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Southern California prior to October indicated most isolates originated from clade 20C that likely emerged from New York via Europe early in the pandemic.
February 10, 2021
Updated quarantine recommendations for vaccinated persons. Fully vaccinated persons who meet criteria will no longer be required to quarantine following an exposure to someone with COVID-19. Additional considerations for patients and residents in healthcare settings are provided.
CDC conducted experiments to assess two ways of improving the fit of medical procedure masks: fitting a cloth mask over a medical procedure mask, and knotting the ear loops of a medical procedure mask and then tucking in and flattening the extra material close to the face. Each modification substantially improved source control and reduced wearer exposure.
February 9, 2021
From September to December 2020, intent to receive COVID-19 vaccination increased from 39.4% to 49.1% among adults and across all priority groups, and nonintent decreased from 38.1% to 32.1%. Despite decreases in nonintent from September to December, younger adults, women, non-Hispanic Black adults, adults living in nonmetropolitan areas, and adults with less education and income, and without health insurance continue to have the highest estimates of nonintent to receive COVID-19 vaccination.
February 8, 2021
Decreased SARS-CoV-2 viral load following vaccination
Beyond their substantial protection of individual vaccinees, it is hoped that the COVID-19 vaccines would reduce viral load in breakthrough infections thereby further suppress onward transmission. Here, analyzing positive SARS-CoV-2 test results following inoculation with the BNT162b2 mRNA vaccine, we find that the viral load is reduced 4-fold for infections occurring 12-28 days after the first dose of vaccine. These reduced viral loads hint to lower infectiousness, further contributing to vaccine impact on virus spread.
This study found that, as of August 2020, the population of Virginia remained largely immunologically naive to the virus.
Variant-proof vaccines — invest now for the next pandemic
The rapid development and delivery of highly effective COVID-19 vaccines less than a year after the emergence of the disease is a huge success story. This was possible, in part, because of certain properties of the coronavirus SARS-CoV-2 that favour vaccine design — in particular, the spike protein on the virus’s surface.
COVID research updates: Why it matters that COVID viruses are losing parts of their genome
Again and again, the new coronavirus has sloughed off small chunks of its genome, leading to changes in a viral protein that is frequently targeted by antibodies.
Pregnancy, Postpartum Care, and COVID-19 Vaccination in 2021
This JAMA Insights review summarizes the epidemiology of SARS-CoV-2 infection in pregnant and lactating women, its effects on perinatal outcomes, and compiles guidance from the Centers for Disease Control and Prevention, the Food and Drug Administration and obstetrics-gynecology specialty organizations on the safety of coronavirus vaccines during pregnancy and while breastfeeding.
COVID-19 Vaccination in Pregnant and Lactating Women
This Viewpoint discusses the need for shared decision-making when counseling pregnant and nursing women about the unstudied benefits and risks COVID-19 vaccination, calling for rigorously designed studies with real-time, proactive data collection to establish evidence as quickly as possible about coronavirus vaccine safety in mothers and their infants.
February 5, 2021
SARS-CoV-2 evolution during treatment of chronic infection
SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE21, and is a major antibody target. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences over 23 time points spanning 101 days. Little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days. However, following convalescent plasma therapy we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and ΔH69/ΔV70 in the S1 N-terminal domain NTD of the Spike protein.
February 4, 2021
Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.
A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19
Current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking.
Merck Statement on Ivermectin use During the COVID-19 Pandemic
It is important to note that, to-date, our analysis has identified:
No scientific basis for a potential therapeutic effect against COVID-19 from pre-clinical studies;
No meaningful evidence for clinical activity or clinical efficacy in patients with COVID-19 disease, and;
A concerning lack of safety data in the majority of studies.
February 3, 2021
Necessity of 2 Doses of the Pfizer and Moderna COVID-19 Vaccines
Two doses of the Pfizer and Moderna COVID-19 vaccines are necessary to confer adequate immunity.
The new vaccines for coronavirus disease 2019 (COVID-19) are highly effective, but controversy exists about whether a second dose should be delayed in order to immunize more people. The second dose is necessary and should be given.
February 2, 2021
Transmission of COVID-19 in 282 clusters in Catalonia, Spain: a cohort study
Scarce data are available on what variables affect the risk of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the development of symptomatic COVID-19, and, particularly, the relationship with viral load. We aimed to analyse data from linked index cases of COVID-19 and their contacts to explore factors associated with transmission of SARS-CoV-2.
A heterologous recombinant adenovirus (rAd)-based vaccine, Gam-COVID-Vac (Sputnik V), showed a good safety profile and induced strong humoral and cellular immune responses in participants in phase 1/2 clinical trials. Here, we report preliminary results on the efficacy and safety of Gam-COVID-Vac from the interim analysis of this phase 3 trial.
February 1, 2021
Combined treatment with methylprednisolone vs IVIG alone was associated with a better course of fever in MIS-C.
As the vaccination program expands, it is critical to ensure efficient and equitable administration to persons in each successive vaccine priority category, especially those at highest risk for infection and severe health outcomes.
January 29, 2021
Response to a COVID-19 Outbreak on a University Campus — Indiana, August 2020
Enhanced testing, timely contact tracing, provision of adequate isolation and quarantine space, increased screening of asymptomatic persons, and communication promoting adherence to mitigation strategies can help control COVID-19 outbreaks on college and university campuses while minimizing disruptions to in-person instruction.
Assessment of the context of each interaction, including mask use, indoor versus outdoor setting, and ventilation, in addition to duration and proximity, can improve identification of high-risk contacts during contact tracing. Postexposure quarantine based on redefined high-risk criteria, combined with testing and environment-specific intensive protocols, can protect communities before and after case identification.
These findings suggest that expanding the amount and duration of unemployment insurance may be an effective approach to reducing food insecurity.
Vaccine Distribution—Equity Left Behind?
Over the past 2 weeks numerous states have announced a major shift in coronavirus disease 2019 (COVID-19) vaccination programs—from a textured approach that includes individual risk factors for morbidity and mortality (eg, age and high-risk medical conditions), occupational risk factors for exposure (eg, first responders and correctional officers), and other societal priorities (eg, essential workers such as teachers, grocery store employees, and public transportation workers) to an approach focused on vaccinating all individuals aged 65 years and older.
Locations administering COVID-19 vaccines should adhere to CDC guidance, including screening recipients for contraindications and precautions, having necessary supplies and staff members available to manage anaphylaxis, implementing recommended postvaccination observation periods, and immediately treating suspected anaphylaxis with intramuscular epinephrine injection.
During California’s stay-at-home order, cervical cancer screening rates among approximately 1.5 million women in the Kaiser Permanente Southern California (KPSC) network decreased approximately 80% compared with baseline. The decrease was similar across all racial/ethnic groups of KPSC and returned to near normal after reopening.
Trends in Outbreak-Associated Cases of COVID-19 — Wisconsin, March–November 2020
COVID-19 surveillance and mitigation planning should be prioritized for highly affected settings such as long-term care facilities, correctional facilities, and colleges and universities, which could represent early indicators of broader community transmission.
January 28, 2021
Remdesivir is a delayed translocation inhibitor of SARS CoV-2 replication
Remdesivir is a nucleoside analog approved by the FDA for treatment of COVID-19. Here, we present a 3.9-Å-resolution cryoEM reconstruction of a remdesivir-stalled RNA-dependent RNA polymerase complex, revealing full incorporation of three copies of remdesivir monophosphate (RMP) and a partially incorporated fourth RMP in the active site. The structure reveals that RMP blocks RNA translocation after incorporation of three bases following RMP, resulting in delayed chain termination, which can guide the rational design of improved antiviral drugs.
January 27, 2021
Meta and consensus forecast of COVID-19 targets
Our aim is to provide two types of probabilistic forecasts of the evolving US COVID-19 outbreak to support public health officials, infectious disease modeling groups, and the general public
De novo design of modular and tunable protein biosensors
Naturally occurring protein switches have been repurposed for developing novel biosensors and reporters for cellular and clinical applications, but the number of such switches is limited, and engineering them is often challenging as each is different. Here, we show that a very general class of protein-based biosensors can be created by inverting the flow of information through de novo designed protein switches in which binding of a peptide key triggers biological outputs of interest.
January 26, 2021
Monoclonal antibodies protect against COVID-19 in a second study
A second company has provided preliminary evidence that proactively infusing healthy people with monoclonal antibodies against SARS-CoV-2 prevents them from developing noticeable symptoms of COVID-19 if they are exposed to the coronavirus.
January 25, 2021
Prospective mapping of viral mutations that escape antibodies used to treat COVID-19
Antibodies are a potential therapy for SARS-CoV-2, but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to SARS-CoV-2’s receptor-binding domain (RBD) affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino-acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2, as well as during in vitro viral escape selections.
January 21, 2021
SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19
In this interim analysis of a phase 2 trial, one of three doses of neutralizing antibody LY-CoV555 appeared to accelerate the natural decline in viral load over time, whereas the other doses had not by day 11.
REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19
In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. Safety outcomes were similar in the combined REGN-COV2 dose groups and the placebo group.
Among 17 rural Wisconsin schools, reported student mask-wearing was high, and the COVID-19 incidence among students and staff members was lower than in the county overall (3,453 versus 5,466 per 100,000). Among 191 cases identified in students and staff members, only seven (3.7%) cases, all among students, were linked to in-school spread.
BBV152 led to tolerable safety outcomes and enhanced immune responses. Both Algel-IMDG formulations were selected for phase 2 immunogenicity trials. Further efficacy trials are warranted.
January 15, 2021
Emergence of SARS-CoV-2 B.1.1.7 Lineage — United States, December 29, 2020–January 12, 2021
The increased transmissibility of the B.1.1.7 variant warrants universal and increased compliance with mitigation strategies, including distancing and masking. Higher vaccination coverage might need to be achieved to protect the public. Genomic sequence analysis through the National SARS-CoV-2 Strain Surveillance program will enable a targeted approach to identifying variants of concern in the United States.
Locations administering COVID-19 vaccines should adhere to CDC guidance for use of COVID-19 vaccines, including screening recipients for contraindications and precautions, having the necessary supplies available to manage anaphylaxis, implementing the recommended postvaccination observation periods, and immediately treating suspected cases of anaphylaxis with intramuscular injection of epinephrine.
January 14, 2021
COVID reinfections are unusual — but could still help the virus to spread
Most people who catch and recover from COVID-19 are likely to be immune for several months afterwards, a study of more than 20,000 health-care workers in the United Kingdom has found.
January 13, 2021
Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19
Among patients hospitalized with Covid-19 who were not receiving mechanical ventilation, transfusion of plasma with higher anti–SARS-CoV-2 IgG antibody levels was associated with a lower risk of death than transfusion of plasma with lower antibody levels.
COVID-19 Trends Among Persons Aged 0–24 Years — United States, March 1–December 12, 2020
To enable safer in-person learning, schools and communities should fully implement and strictly adhere to multiple mitigation strategies, especially universal and proper mask wearing, to reduce both school and community COVID-19 incidence to help protect students, teachers, and staff members from COVID-19.
Interim Results of a Phase 1–2a Trial of Ad26.COV2.S Covid-19 Vaccine
The safety and immunogenicity profiles of Ad26.COV2.S support further development of this vaccine candidate.
(A Little) Clarity on Convalescent Plasma for Covid-19
Passive immunotherapy has been used since the late 19th century, and in 1901, the first Nobel Prize in Physiology or Medicine was awarded for serum therapy for patients with diphtheria. During the 1918 pandemic, serum from convalescent patients was used to treat influenza, with some apparent success.
January 12, 2021
Immunological characteristics govern the transition of COVID-19 to endemicity
We are currently faced with the question of how the CoV-2 severity may change in the years ahead. Our analysis of immunological and epidemiological data on endemic human coronaviruses (HCoVs) shows that infection-blocking immunity wanes rapidly, but disease-reducing immunity is long-lived. Our model, incorporating these components of immunity, recapitulates both the current severity of CoV-2 and the benign nature of HCoVs, suggesting that once the endemic phase is reached and primary exposure is in childhood, CoV-2 may be no more virulent than the common cold.
January 9, 2021
Predictors of intention to vaccinate against COVID-19: Results of a nationwide survey
Nearly two in five adults were hesitant about getting a COVID-19 vaccine. Male, older, white, married, and higher SES individuals more likely to vaccinate. Republicans and Fox News viewers were less likely to vaccinate. Being currently immunized against influenza predicted COVID-19 vaccination intent. A better understanding of COVID-19 vaccination hesitancy is needed.
January 8, 2021
Additional implementation of effective mitigation activities at colleges and universities with in-person instruction could minimize on-campus COVID-19 transmission and reduce county-level incidence.
Among young, healthy athletes, the probability of receiving positive test results after day 10 of quarantine is low. A shorter quarantine after COVID-19 exposure could increase adherence but still poses a small residual risk for transmission.
6-month consequences of COVID-19 in patients discharged from hospital: a cohort study
At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery.
Rates of COVID-19 among nursing home residents and staff members increased during June and July 2020, and again in November. Trends in reported COVID-19 cases among nursing home residents and staff members were similar to trends in incidence of COVID-19 in surrounding communities.
Candida auris Outbreak in a COVID-19 Specialty Care Unit — Florida, July–August 2020
In July 2020, the Florida Department of Health was alerted to three Candida auris bloodstream infections and one urinary tract infection in four patients with coronavirus disease 2019 (COVID-19) who received care in the same dedicated COVID-19 unit of an acute care hospital (hospital A).
January 7, 2021
SARS-CoV-2 Transmission From People Without COVID-19 Symptoms
The findings of this study suggest that the identification and isolation of persons with symptomatic COVID-19 alone will not control the ongoing spread of SARS-CoV-2.
January 6, 2021
During December 14–23, 2020, monitoring by the Vaccine Adverse Event Reporting System detected 21 cases of anaphylaxis after administration of a reported 1,893,360 first doses of the Pfizer-BioNTech COVID-19 vaccine (11.1 cases per million doses); 71% of these occurred within 15 minutes of vaccination.
Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection
Understanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months post-infection.
Genetic Variants of SARS-CoV-2—What Do They Mean?
Over the course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the clinical, scientific, and public health communities have had to respond to new viral genetic variants. Each one has triggered a flurry of media attention, a range of reactions from the scientific community, and calls from governments to either “stay calm” or pursue immediate countermeasures.
COVID-19 and mental health deterioration by ethnicity and gender in the UK
We use the UK Household Longitudinal Study and compare pre-COVID-19 pandemic (2017-2019) and during-COVID-19 pandemic data (April 2020) for the same group of individuals to assess and quantify changes in mental health as measured by changes in the GHQ-12 (General Health Questionnaire), among ethnic groups in the UK. We confirm the previously documented average deterioration in mental health for the whole sample of individuals interviewed before and during the COVID-19 pandemic.
Through molecular simulation, possible mechanisms of action of the nucleotide-analogue inhibitors remdesivir, favilavir, and ribavirin on the RNA-dependent RNA polymerase of SARS-CoV-2 are elucidated.
January 1, 2021
Compared with real-time reverse transcription–polymerase chain reaction (RT-PCR) testing, the Sofia antigen test had a sensitivity of 80.0% and specificity of 98.9% among symptomatic persons; accuracy was lower (sensitivity 41.2% and specificity 98.4%) when used for screening of asymptomatic persons.
Among persons exposed to COVID-19 in the household who were asymptomatic and had negative laboratory test results through 7 days after symptom onset in the index patient, 19% experienced symptoms or received positive test results in the following week.
December 23, 2020
Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers
The presence of anti-spike or anti-nucleocapsid IgG antibodies was associated with a substantially reduced risk of SARS-CoV-2 reinfection in the ensuing 6 months.
December 22, 2020
On December 20, ACIP updated interim vaccine allocation recommendations. In Phase 1b, COVID-19 vaccine should be offered to persons aged ≥75 years and non–health care frontline essential workers, and in Phase 1c, to persons aged 65–74 years, persons aged 16–64 years with high-risk medical conditions, and essential workers not included in Phase 1b.
Implications of the Emerging SARS-CoV-2 Variant VUI 202012/01
A new variant strain of SARS-CoV-2 that contains a series of mutations has been described in the United Kingdom (UK) and become highly prevalent in London and southeast England. Based on these mutations, this variant strain has been predicted to potentially be more rapidly transmissible than other circulating strains of SARS-CoV-2.
A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19
Monoclonal antibody LY-CoV555, when co-administered with remdesivir, did not demonstrate efficacy among hospitalized patients who had Covid-19 without end-organ failure.
COVID-19 risk, disparities and outcomes in patients with chronic liver disease in the United States
Patients with CLD, especially African Americans, were at increased risk for COVID-19, highlighting the need to protect these patients from exposure to virus infection.
December 21, 2020
COVID research updates: How 90% of French COVID cases evaded detection
In the weeks after France ended its first lockdown, nine residents with COVID-19 symptoms went undetected for every person confirmed to have the disease — despite a nationwide surveillance programme.
What’s your risk of catching COVID? These tools help you to find out
A look at apps that predict the chance of infection and illness depending on what you’re doing and where you are.
December 18, 2020
Recently a distinct phylogenetic cluster (named lineage B.1.1.7) was detected within the COG-UK surveillance dataset. This cluster has been growing rapidly over the past 4 weeks and since been observed in other UK locations, indicating further spread.
During July 11–17, 2020, 963 (95.4%) of 1,009 Health Resources and Services Administration–funded health centers that responded to a voluntary weekly survey reported providing telehealth services. Health centers in urban areas were more likely to provide >30% of visits virtually than were those in rural areas.
December 17, 2020
Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia
Coronavirus disease 2019 (Covid-19) pneumonia is often associated with hyperinflammation. Despite the disproportionate incidence of Covid-19 among underserved and racial and ethnic minority populations, the safety and efficacy of the anti–interleukin-6 receptor antibody tocilizumab in patients from these populations who are hospitalized with Covid-19 pneumonia are unclear.
REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19
Recent data suggest that complications and death from coronavirus disease 2019 (Covid-19) may be related to high viral loads.
A toolkit for the collection of thrombosis-related data elements in COVID-19 clinical studies
Thrombosis has emerged as an important complication of coronavirus disease 2019 (COVID-19), particularly among individuals with severe illness. However, the precise incidence of thrombotic events remains uncertain due to differences in study design, patient populations, outcome ascertainment, event definitions, and reporting. In an effort to overcome some of these challenges and promote standardized data collection and reporting in clinical studies, the American Society of Hematology Research Collaborative COVID-19 Non-Malignant Hematology Task Force, in collaboration with the International Society on Thrombosis and Haemostasis COVID-19 Task Force, developed sets of data elements in the following domains: venous thromboembolism, myocardial infarction, stroke/transient ischemic attack, peripheral arterial thrombosis, bleeding, laboratory investigations, and antithrombotic therapy.
December 16, 2020
Mechanisms of Atomization from Rotary Dental Instruments and Its Mitigation
Since the onset of coronavirus disease 2019, the potential risk of dental procedural generated spray emissions (including aerosols and splatters), for severe acute respiratory syndrome coronavirus 2 transmission, has challenged care providers and policy makers alike. New studies have described the production and dissemination of sprays during simulated dental procedures, but findings lack generalizability beyond their measurements setting.
Emergence of a Highly Fit SARS-CoV-2 Variant
Sarbecoviruses have emerged twice in the 21st century, causing a worldwide epidemic and pandemic. The ongoing pandemic of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused unprecedented disruption of human society.
The S1 protein of SARS-CoV-2 crosses the blood–brain barrier in mice
It is unclear whether severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019, can enter the brain. Severe acute respiratory syndrome coronavirus 2 binds to cells via the S1 subunit of its spike protein. We show that intravenously injected radioiodinated S1 (I-S1) readily crossed the blood–brain barrier in male mice, was taken up by brain regions and entered the parenchymal brain space. I-S1 was also taken up by the lung, spleen, kidney and liver. Intranasally administered I-S1 also entered the brain, although at levels roughly ten times lower than after intravenous administration.
Coronavirus disease 2019 (COVID-19) has caused a marked increase in all-cause deaths in the US, mostly among older adults. Although the burden of COVID-19 among hospitalized younger adults has been described, fewer data focus on mortality in this demographic, owing to lower case-fatality rates.
Surgeon Fills COVID-19 Testing Gap in Philadelphia’s Black Neighborhoods
As coronavirus disease 2019 (COVID-19) surged last spring, pediatric surgeon Ala Stanford, MD, heard from Black residents in her hometown of Philadelphia, Pennsylvania, who had symptoms but were hitting roadblocks in getting tested.
December 15, 2020
Rapid increases in cases of COVID-19 were observed in multiple cities in Iran towards the start of the pandemic. However, the true infection rate remains unknown. We aimed to assess the seroprevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 18 cities of Iran as an indicator of the infection rate.
The CNS manifestations of COVID-19 in children have primarily been described in case reports, which limit the ability to appreciate the full spectrum of the disease in paediatric patients. We aimed to identify enough cases that could be evaluated in aggregate to better understand the neuroimaging manifestations of COVID-19 in the paediatric population.
December 14, 2020
Severe acute respiratory syndrome coronavirus 2 causes direct damage to the airway epithelium, enabling aspergillus invasion. Reports of COVID-19-associated pulmonary aspergillosis have raised concerns about it worsening the disease course of COVID-19 and increasing mortality. Additionally, the first cases of COVID-19-associated pulmonary aspergillosis caused by azole-resistant aspergillus have been reported.
Although more patients are surviving severe coronavirus disease 2019 (COVID-19), there are limited data on outcomes after initial hospitalization. We therefore measured the rate of readmission, reasons for readmission, and rate of death after hospital discharge among patients with COVID-19 in the nationwide Veterans Affairs (VA) health care system.
COVID research updates: A drug duo that helps people with severe COVID
A combination of the drugs baricitinib and remdesivir shaved one day off the recovery of people hospitalized with COVID-19.
December 13, 2020
On December 12, 2020, after an explicit, evidence-based review of all available data, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for use of the Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years for the prevention of COVID-19.
December 11, 2020
Genetic mechanisms of critical illness in Covid-19
Host-mediated lung inflammation is present, and drives mortality, in critical illness caused by Covid-19. Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.
The early clinical course of COVID-19 can be difficult to distinguish from other illnesses driving presentation to hospital. However, viral-specific PCR testing has limited sensitivity and results can take up to 72 h for operational reasons. We aimed to develop and validate two early-detection models for COVID-19, screening for the disease among patients attending the emergency department and the subset being admitted to hospital, using routinely collected health-care data (laboratory tests, blood gas measurements, and vital signs). These data are typically available within the first hour of presentation to hospitals in high-income and middle-income countries, within the existing laboratory infrastructure.
Whether HIV infection is associated with risk of death due to COVID-19 is unclear. We aimed to investigate this association in a large-scale population-based study in England.
An EUA for Bamlanivimab—A Monoclonal Antibody for COVID-19
Monoclonal antibodies, such as bamlanivimab, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation. Bamlanivimab is not authorized for use in patients who are hospitalized or require oxygen therapy because of COVID-19.
Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19
Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known.
Costs per student for implementation of strategies range from a mean of $55 (materials and consumables only) to $442 (materials and consumables, additional custodial staff members, and potential additional transportation). Incremental costs across states range from an additional 0.3% to 7.1% in costs needed above reported fiscal year 2018 school expenditures per student.
During the COVID-19 pandemic, the total number of emergency department visits related to child abuse and neglect decreased, but the percentage of such visits resulting in hospitalization increased, compared with 2019.
Among parents of school-aged children who participated in an Internet panel survey, racial and ethnic minority parents were more concerned about some aspects of school reopening, such as compliance with mitigation measures, safety, and their child contracting or bringing home COVID-19, than were non-Hispanic White parents.
December 10. 2020
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently.
December 9, 2020
Development and external validation of a prognostic tool for COVID-19 critical disease
The rapid spread of coronavirus disease 2019 (COVID-19) revealed significant constraints in critical care capacity. In anticipation of subsequent waves, reliable prediction of disease severity is essential for critical care capacity management and may enable earlier targeted interventions to improve patient outcomes.
December 7, 2020
Head Start and Early Head Start programs successfully implemented CDC-recommended guidance and other ancillary measures for child care programs that remained open, allowing them to continue offering in-person learning. These approaches were documented to guide implementation of mitigation strategies in child care settings.
December 4, 2020
COVID-19 pandemic control requires a multipronged application of evidence-based strategies while improving health equity: universal face mask use, physical distancing, avoiding nonessential indoor spaces, increasing testing, prompt quarantine of exposed persons, safeguarding those at increased risk for severe illness or death, protecting essential workers, postponing travel, enhancing ventilation and hand hygiene, and achieving widespread COVID-19 vaccination coverage.
In this randomized clinical trial that involved 5260 adults and was conducted over 3 influenza seasons, there was no significant difference in the time to first occurrence of all-cause death or cardiopulmonary hospitalization during each enrolling season for those in the high-dose group vs the standard-dose group (hazard ratio, 1.06).
December 3, 2020
Metformin was significantly associated with reduced mortality in women with obesity or type 2 diabetes who were admitted to hospital for COVID-19. Prospective studies are needed to understand mechanism and causality. If findings are reproducible, metformin could be widely distributed for prevention of COVID-19 mortality, because it is safe and inexpensive.
Our method could help to detect rapid case increases in regions where government testing provision is lower. Self-reported data from mobile applications can provide an agile resource to inform policy makers during a quickly moving pandemic, serving as a complementary resource to more traditional instruments for disease surveillance.
December 1, 2020
Successful double-lung transplantation from a donor previously infected with SARS-CoV-2
In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resulting respiratory disease, COVID-19, emerged. As the pandemic continues, with more than 62 million people with documented SARS-CoV-2 infection, a growing number of potential organ donors will have been infected.
A New Jersey hospital reported a cluster of 34 CRAB cases that peaked during a surge in COVID-19 hospitalizations. Strategies to preserve continuity of care led to deviations in IPC practices; CRAB cases decreased when normal operations resumed.
November 27, 2020
Among 156 frontline health care personnel who had positive SARS-CoV-2 antibody test results in spring 2020, 94% experienced a decline at repeat testing approximately 60 days later, and 28% seroreverted to below the threshold of positivity. Participants with higher initial antibody responses were more likely to have antibodies detected at the follow-up test than were those who had a lower initial antibody response.
The impact of gatherings as a source of virus transmission underscores the importance of reducing the number of attendees at gatherings, using face masks, and encouraging physical distancing to prevent ongoing transmission of SARS-CoV-2. Furthermore, these findings demonstrate the rationale for consistent mitigation measures across states.
Countywide mask mandates appear to have contributed to the mitigation of COVID-19 transmission in mandated counties. Community-level mitigation strategies emphasizing use of masks, physical distancing, staying at home when ill, and enhanced hygiene practices can help reduce the transmission of SARS-CoV-2.
November 24, 2020
A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19
Postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053. opens in new tab.)
A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia
Convalescent plasma is frequently administered to patients with Covid-19 and has been reported, largely on the basis of observational data, to improve clinical outcomes. Minimal data are available from adequately powered randomized, controlled trials.
November 23, 2020
In addition to scientific data and implementation feasibility, four ethical principles will assist ACIP in formulating recommendations for the initial allocation of COVID-19 vaccine: 1) maximizing benefits and minimizing harms; 2) promoting justice; 3) mitigating health inequities; and 4) promoting transparency.
Serious psychological distress was reported by 13.6% of US adults in April 2020 vs 3.9% in 2018.1 How psychological distress has changed over the course of the coronavirus disease 2019 (COVID-19) pandemic is unknown.
Diagnosis, Management, and Pathophysiology of Arterial and Venous Thrombosis in COVID-19
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with arterial and venous thrombotic complications. In a US registry of patients with coronavirus disease 2019 (COVID-19), thrombotic complications occurred in 2.6% of 229 non–critically ill hospitalized patients and in 35.3% of 170 hospitalized critically ill patients.
November 20, 2020
COVID research updates: Immune responses to coronavirus persist beyond 6 months
Nature wades through the literature on the new coronavirus — and summarizes key papers as they appear.
Effect of COVID-19 on maternal and neonatal services
Globally, the COVID-19 pandemic has badly affected almost all sectors, including health. Ashish KC and colleagues1 showed that, in Nepal, institutional birth rates declined by almost 50% and that institutional neonatal mortality increased by more than 200% in selected referral hospitals between January and May, 2020. However, convincing explanations for such a drastic change in maternal and neonatal health services are yet to be explored. Here we aim to provide possible reasons for such a decline in maternal and neonatal health services and provide perspectives on the potential ways to improve them.
November 19, 2020
These findings suggest that SARS-CoV-2 infection in pregnancy is not associated with adverse pregnancy outcomes.
Viral load kinetics and duration of viral shedding are important determinants for disease transmission. We aimed to characterise viral load dynamics, duration of viral RNA shedding, and viable virus shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in various body fluids, and to compare SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) viral dynamics.
November 18, 2020
Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19, in young adults, and now describe the safety and immunogenicity of this vaccine in a wider range of participants, including adults aged 70 years and older.
November 13, 2020
Using viral load quantifications and super-resolution microscopy, baricitinib exerts activity rapidly through the inhibition of host proteins (numb associated kinases), uniquely amongst anti-virals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication and the cytokine storm, and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivizes further randomized controlled trials.
A wedding reception with 55 persons in a rural Maine town led to COVID-19 outbreaks in the local community, as well as at a long-term care facility and a correctional facility in other counties. Overall, 177 COVID-19 cases were linked to the event, including seven hospitalizations and seven deaths (four in hospitalized persons). Investigation revealed noncompliance with CDC’s recommended mitigation measures.
November 12, 2020
Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19
In this randomized trial that included 152 adult outpatients with confirmed COVID-19 and symptom onset within 7 days, clinical deterioration occurred in 0 patients treated with fluvoxamine vs 6 (8.3%) patients treated with placebo over 15 days, a difference that was statistically significant.
November 11, 2020
An Outbreak of Covid-19 on an Aircraft Carrier
An outbreak of coronavirus disease 2019 (Covid-19) occurred on the U.S.S. Theodore Roosevelt, a nuclear-powered aircraft carrier with a crew of 4779 personnel.
SARS-CoV-2 Transmission among Marine Recruits during Quarantine
The efficacy of public health measures to control the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been well studied in young adults.
November 10, 2020
Mobility network models of COVID-19 explain inequities and inform reopening
The COVID-19 pandemic dramatically changed human mobility patterns, necessitating epidemiological models which capture the effects of changes in mobility on virus spread1. We introduce a metapopulation SEIR model that integrates fine-grained, dynamic mobility networks to simulate the spread of SARS-CoV-2 in 10 of the largest US metropolitan statistical areas.
November 9, 2020
Adverse mental health consequences of COVID-19, including anxiety and depression, have been widely predicted but not yet accurately measured. There are a range of physical health risk factors for COVID-19, but it is not known if there are also psychiatric risk factors.
November 3, 2020
COVID-19 is characterized by extensive alveolar damage (41/41 of patients) and thrombosis of the lung micro- and macro-vasculature (29/41, 71%). Thrombi were in different stages of organization, consistent with their local origin. Pneumocytes and endothelial cells contained viral RNA even at the later stages of the disease.
November 2, 2020
Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19
Patients with COVID-19 are at high risk for thrombotic arterial and venous occlusions. Lung histopathology often reveals fibrin-based occlusions in the small blood vessels of patients who succumb to the disease.
Among 3,912 infants with known gestational age born to women with SARS-CoV-2 infection, 12.9% were preterm (<37 weeks), higher than a national estimate of 10.2%. Among 610 (21.3%) infants with testing results, 2.6% had positive SARS-CoV-2 results, primarily those born to women with infection at delivery.
In an analysis of approximately 400,000 women aged 15–44 years with symptomatic COVID-19, intensive care unit admission, invasive ventilation, extracorporeal membrane oxygenation, and death were more likely in pregnant women than in nonpregnant women.
Science Denial and COVID Conspiracy Theories
The US public health response to coronavirus disease 2019 (COVID-19) has been dismal, characterized by antimask behavior, antivaccine beliefs, conspiracy theories about the origins of COVID-19, and vocal support by elected officials for unproven therapies.
November 2020
Propolis, a resinous material produced by honey bees from plant exudates, has long been used in traditional herbal medicine and is widely consumed as a health aid and immune system booster. The COVID-19 pandemic has renewed interest in propolis products worldwide; fortunately, various aspects of the SARS-CoV-2 infection mechanism are potential targets for propolis compounds.
Quantitative phylogenomic evidence reveals a spatially structured SARS-CoV-2 diversity
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent RNA virus that spread around the planet in about 4 months. The consequences of this rapid dispersion are under investigation. In this work, we analyzed thousands of genomes and protein sequences from Africa, America, Asia, Europe, and Oceania.
October 30, 2020
Peripheral Oxygen Saturation in Older Persons Wearing Nonmedical Face Masks in Community Settings
Based on the evidence that nonmedical face masks prevent the spread of severe acute respiratory syndrome coronavirus, many governments are mandating the wearing of masks in the community. However, fueled partly by claims on social media that masks can cause hypoxia and are therefore dangerous, concerns have emerged about the safety of wearing face masks. We examined whether wearing nonmedical face masks was associated with a change in oxygen saturation.
Transmission of SARS-COV-2 Infections in Households — Tennessee and Wisconsin, April–September 2020
Findings from a prospective household study with intensive daily observation for ≥7 consecutive days indicate that transmission of SARS-CoV-2 among household members was frequent from either children or adults.
COVID-19 Outbreak at an Overnight Summer School Retreat ― Wisconsin, July–August 2020
During July 2–August 11, 2020, a COVID-19 outbreak at an overnight high-school retreat likely began with a single student who had received a negative SARS-CoV-2 molecular test result <1 week before the retreat and led to 116 (76%) diagnosed COVID-19 cases among attendees.
October 29, 2020
Elective Surgery during the Covid-19 Pandemic
You are a physician leader on a senior committee that is responsible for your hospital’s Covid-19 response. For the past week, the hospital census has been over 90% of capacity, and almost all usual intensive care unit (ICU) beds have been occupied, more than half with patients who have Covid-19. You are using 10% of the ICU surge capacity created by your hospital to accommodate patients with Covid-19.
October 28, 2020
SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (Covid-19), which is most frequently mild yet can be severe and life-threatening. Virus-neutralizing monoclonal antibodies are predicted to reduce viral load, ameliorate symptoms, and prevent hospitalization.
October 27, 2020
Shifting Hydroxychloroquine Patterns Raise Concern
The number of hydroxychloroquine prescriptions by specialists who don’t typically prescribe the drug skyrocketed after preliminary reports in March suggested potential benefits for patients with coronavirus disease 2019 (COVID-19).
October 21, 2020
CDC Revised Statement on Close Contact
Someone who was within 6 feet of an infected person for a cumulative total of 15 minutes or more over a 24-hour period* starting from 2 days before illness onset (or, for asymptomatic patients, 2 days prior to test specimen collection) until the time the patient is isolated.
* Individual exposures added together over a 24-hour period (e.g., three 5-minute exposures for a total of 15 minutes). Data are limited, making it difficult to precisely define “close contact;” however, 15 cumulative minutes of exposure at a distance of 6 feet or less can be used as an operational definition for contact investigation.
Data are limited to precisely define “close contact”; however, 15 minutes of close exposure is used as an operational definition for contact tracing investigations in many settings. Additional factors to consider when defining close contact include proximity, the duration of exposure, whether the infected person has symptoms, whether the infected person was likely to generate respiratory aerosols, and environmental factors such as adequacy of ventilation and crowding. A primary purpose of contact tracing is to identify persons with higher risk exposures and therefore higher probabilities of developing infection, which can guide decisions on quarantining and work restrictions. Although the initial assessment did not suggest that the officer had close contact exposures, detailed review of video footage identified that the cumulative duration of exposures exceeded 15 minutes.
The Challenges of Expanding Rapid Tests to Curb COVID-19
If Michael Mina, MD, PhD, had his way, testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) would become simple and routine—as easy as brushing one’s teeth in the morning.
October 20, 2020
Overall, an estimated 299,028 excess deaths occurred from late January through October 3, 2020, with 198,081 (66%) excess deaths attributed to COVID-19. The largest percentage increases were seen among adults aged 25–44 years and among Hispanic or Latino persons.
Hospitalized patients with COVID-19 in the Veterans Health Administration had a more than five times higher risk for in-hospital death and increased risk for 17 respiratory and nonrespiratory complications than did hospitalized patients with influenza. The risks for sepsis and respiratory, neurologic, and renal complications of COVID-19 were higher among non-Hispanic Black or African American and Hispanic patients than among non-Hispanic White patients.
Latin America’s embrace of an unproven COVID treatment is hindering drug trials
As much of the world waits for an effective vaccine to curb the COVID-19 pandemic, some in Latin America are turning to an unproven treatment. There isn’t enough evidence that the drug, ivermectin, is safe or effective as a coronavirus therapy, however. So researchers are cautioning against using it outside clinical trials.
October 16, 2020
COVID-19 messages should continue promoting hand hygiene, particularly among men and young adults. Messages addressing COVID-19 risk perceptions and making handwashing accessible and hand sanitizer available by facilities in public settings should be considered to encourage and facilitate hand hygiene.
CDC works with other federal agencies to identify counties with increasing coronavirus disease 2019 (COVID-19) incidence (hotspots) and offers support to state, tribal, local, and territorial health departments to limit the spread of SARS-CoV-2, the virus that causes COVID-19 (1). Understanding whether increasing incidence in hotspot counties is predominantly occurring in specific age groups is important for identifying opportunities to prevent or reduce transmission.
An Outbreak of COVID-19 Associated with a Recreational Hockey Game — Florida, June 2020
On June 16, 2020, a recreational ice hockey game was played at an ice rink in the Tampa Bay, Florida, metropolitan area. Teams A and B, each consisting of 11 players (typically six on the ice and five on the bench at any given time), included men aged 19–53 years. During the 5 days after the game, 15 persons (14 of the 22 players and a rink staff member) experienced signs and symptoms compatible with coronavirus disease 2019 (COVID-19)*; 13 of the 15 ill persons had positive laboratory test results indicating infection with SARS-CoV-2, the virus that causes COVID-19.
Identifying factors that influence risk for COVID-19 exposure and framing messaging to target those factors could help persuade young adults to adhere to public health guidelines that prevent the spread of COVID-19. Providing clear and consistent messages regarding the need for and effectiveness of masks could help increase widespread adoption of evidence-based guidance.
October 19, 2020
Herd Immunity and Implications for SARS-CoV-2 Control
Herd immunity, also known as indirect protection, community immunity, or community protection, refers to the protection of susceptible individuals against an infection when a sufficiently large proportion of immune individuals exist in a population. In other words, herd immunity is the inability of infected individuals to propagate an epidemic outbreak due to lack of contact with sufficient numbers of susceptible individuals.
October 16, 2020
Race, Ethnicity, and Age Trends in Persons Who Died from COVID-19 — United States, May–August 2020
Analysis of 114,411 COVID-19–associated deaths reported to National Vital Statistics System during May–August 2020, found that 51.3% of decedents were non-Hispanic White, 24.2% were Hispanic or Latino (Hispanic), and 18.7% were non-Hispanic Black. The percentage of Hispanic decedents increased from 16.3% in May to 26.4% in August.
COVID-19 in Spain: a predictable storm?
As of Oct 12, there have been 861 112 confirmed cases and 32 929 deaths due to COVID-19 in Spain. More than 63 000 health-care workers have been infected. Spain was one of the most affected countries during the first wave of COVID-19 (March to June), and it has now been hit hard again by a second wave of COVID-19 infections.
October 15, 2020
Scientific consensus on the COVID-19 pandemic: we need to act now
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 35 million people globally, with more than 1 million deaths recorded by WHO as of Oct 12, 2020. As a second wave of COVID-19 affects Europe, and with winter approaching, we need clear communication about the risks posed by COVID-19 and effective strategies to combat them. Here, we share our view of the current evidence-based consensus on COVID-19.
October 14, 2020
The Coronavirus Disease 2019 (COVID-19) pandemic has changed many social, economic, environmental and healthcare determinants of health. We applied an ensemble of 16 Bayesian models to vital statistics data to estimate the all-cause mortality effect of the pandemic for 21 industrialized countries.
Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (Covid-19), have spread to millions of persons worldwide.
Clinicians are facing important emotional stressors during the Covid-19 pandemic, including grief from seeing so many patients die, fears of contracting the virus and infecting their family members, and anger over health care disparities and other systems failures. For some, these stressors have caused or exacerbated burnout, depression, or post-traumatic stress disorder, and they have been implicated in suicides.
October 13, 2020
COVID-19 in New Zealand and the impact of the national response: a descriptive epidemiological study
In early 2020, during the COVID-19 pandemic, New Zealand implemented graduated, risk-informed national COVID-19 suppression measures aimed at disease elimination. We investigated their impacts on the epidemiology of the first wave of COVID-19 in the country and response performance measures.
Preterm birth is the leading cause of child mortality globally, with many survivors experiencing long-term adverse consequences. Preliminary evidence suggests that numbers of preterm births greatly reduced following implementation of policy measures aimed at mitigating the effects of the COVID-19 pandemic. We aimed to study the impact of the COVID-19 mitigation measures implemented in the Netherlands in a stepwise fashion on March 9, March 15, and March 23, 2020, on the incidence of preterm birth.
October 12, 2020
What reinfections mean for COVID-19
One of the key questions in predicting the course of the COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is how well and how long the immune responses protect the host from reinfection. For some viruses, the first infection can provide lifelong immunity; for seasonal coronaviruses, protective immunity is short-lived.
October 9, 2020
Understanding whether increasing incidence in hotspot counties is predominantly occurring in specific age groups is important for identifying opportunities to prevent or reduce transmission. The percentage of positive SARS-CoV-2 reverse transcription–polymerase chain reaction (RT-PCR) test results (percent positivity) is an important indicator of community transmission.
In Winnebago County, Wisconsin, perceived low severity of disease outcome; perceived responsibility to others; peer pressure; and exposure to misinformation, conflicting messages, or opposing views regarding masks were identified as drivers of behaviors that might influence risk for COVID-19 exposure among young adults.
COVID research updates: Dense cities should brace for long coronavirus outbreaks
The new coronavirus tears through areas where residents generally keep to their own small, close-knit communities. But the virus takes its time spreading in crowded cities where residents of different neighbourhoods tend to intermingle, ultimately infecting more people than in the relatively isolated areas.
October 8, 2020
Point-of-care testing is associated with large reductions in time to results and could lead to improvements in infection control measures and patient flow compared with centralised laboratory PCR testing.
Remdesivir for the Treatment of Covid-19 — Final Report
We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days.
October 7, 2020
Covid-19, Ebola, and HIV — Leveraging Lessons to Maximize Impact
As researchers who have long experience with HIV/AIDS prevention, vaccines, and therapies, some of whom also have experience with Ebola, we believe it is critical to build the response to the Covid-19 pandemic on lessons from the HIV pandemic and recent Ebola outbreaks.
Lessons We’ve Learned — Covid-19 and the Undocumented Latinx Community
In March 2020, when there were 30,000 confirmed Covid-19 cases in the United States, one of us wrote about the pandemic’s effects on undocumented immigrants.1 By August, there were about 50,000 new U.S. cases per day, and we had spent several months caring for patients with Covid-19.
Seizing the Teachable Moment — Lessons from Eisenhower’s Heart Attack
One reason to study history is to avoid repeating past mistakes; another is to understand what went right.
Improving Clinical Trial Enrollment — In the Covid-19 Era and Beyond
More than 3 million people in the United States are known to have been infected with SARS-CoV-2.1 If every study registered on clinicaltrials.gov as of mid-June meets its target enrollment, less than 4% of those diagnosed with Covid-19 will have been enrolled in a randomized, controlled trial. In the face of a new disease in dire need of proven treatments, every patient not offered enrollment in a well-designed, well-conducted study represents a missed opportunity to advance scientific knowledge, develop therapeutic strategies, and ultimately improve care for everyone who will come next.
October 6, 2020
The number of COVID-19 cases in Arizona stabilized and then decreased after sustained implementation and enforcement of statewide and locally enhanced mitigation measures, beginning approximately 2 weeks after implementation and enforcement of mask mandates and enhanced sanitations practices began on June 17; further decreases were observed during July 13–August 7, after statewide limitations and closures of certain services and businesses.
COVID research updates: Teenager spreads coronavirus on family holiday
A 13-year-old girl gave the new coronavirus to her grandparents and 9 other relatives who occupied the same holiday house for up to 3½ weeks, confirming that adolescents can seed clusters of COVID-19 cases.
October 5, 2020
COVID-19 can sometimes be spread by airborne transmission
Some infections can be spread by exposure to virus in small droplets and particles that can linger in the air for minutes to hours. These viruses may be able to infect people who are further than 6 feet away from the person who is infected or after that person has left the space.
This kind of spread is referred to as airborne transmission and is an important way that infections like tuberculosis, measles, and chicken pox are spread.
There is evidence that under certain conditions, people with COVID-19 seem to have infected others who were more than 6 feet away. These transmissions occurred within enclosed spaces that had inadequate ventilation.
There is increasing evidence that children and adolescents can efficiently transmit SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1–3). During July–August 2020, four state health departments and CDC investigated a COVID-19 outbreak that occurred during a 3-week family gathering of five households in which an adolescent aged 13 years was the index and suspected primary patient; 11 subsequent cases occurred.
Long-term Health Consequences of COVID-19
With more than 30 million documented infections and 1 million deaths worldwide, the coronavirus disease 2019 (COVID-19) pandemic continues unabated. The clinical spectrum of severe acute respiratory syndrome coronavirus (SARS-CoV) 2 infection ranges from asymptomatic infection to life-threatening and fatal disease. Current estimates are that approximately 20 million people globally have “recovered”; however, clinicians are observing and reading reports of patients with persistent severe symptoms and even substantial end-organ dysfunction after SARS-CoV-2 infection.
Preserving Elective Surgeries in the COVID-19 Pandemic and the Future
Cancel everything” has trended as a hashtag during the coronavirus disease 2019 (COVID-19) pandemic, and for good reason. The pandemic has touched virtually every aspect of society, substantially altering, and at its onset halting, the very ways nearly every person in the United States works, learns, lives, and maintains health.
Frequent neurologic manifestations and encephalopathy‐associated morbidity in Covid‐19 patients
Neurologic manifestations occur in most hospitalized Covid‐19 patients. Encephalopathy was associated with increased morbidity and mortality, independent of respiratory disease severity.
October 2, 2020
Clinical suspicion and indicated SARS-CoV-2 testing, including antibody testing, might be needed to recognize and treat adults with MIS-A. Further research is needed to understand the pathogenesis and long-term effects of this condition. Ultimately, the recognition of MIS-A reinforces the need for prevention efforts to limit spread of SARS-CoV-2.
A call for diagnostic tests to report viral load
Ever since the coronavirus pandemic began, battles have raged over testing: Which tests should be given, to whom, and how often? Now, epidemiologists and public health experts are opening a new debate. They say testing centers should report not just whether a person is positive, but also a number known as the cycle threshold (CT) value, which indicates how much virus an infected person harbors.
October 1, 2020
Risk of COVID-19 During Air Travel
The risk of contracting coronavirus disease 2019 (COVID-19) during air travel is lower than from an office building, classroom, supermarket, or commuter train.
Ensuring Uptake of Vaccines against SARS-CoV-2
As Covid-19 continues to exact a heavy toll, development of a vaccine appears the most promising means of restoring normalcy to civil life. Perhaps no scientific breakthrough is more eagerly anticipated. But bringing a vaccine to market is only half the challenge; also critical is ensuring a high enough vaccination rate to achieve herd immunity.
September 30, 2020
COVID-19 and Heart Failure With Preserved Ejection Fraction
Patients with preexisting cardiovascular disease (CVD) who develop coronavirus disease 2019 (COVID-19) have worse outcomes than patients without CVD. Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly or indirectly lead to myocardial injury. Although fulminant viral myocarditis due to COVID-19 appears to be uncommon, recent data, although limited, suggest that direct myocardial injury may occur in some individuals.
Rethinking Covid-19 Test Sensitivity — A Strategy for Containment
It’s time to change how we think about the sensitivity of testing for Covid-19. The Food and Drug Administration (FDA) and the scientific community are currently almost exclusively focused on test sensitivity, a measure of how well an individual assay can detect viral protein or RNA molecules. Critically, this measure neglects the context of how the test is being used.
September 29, 2020
Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults
Testing of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased incidences of illness and death from coronavirus disease 2019 (Covid-19) have been associated with an older age.
Multiple COVID-19 Clusters on a University Campus — North Carolina, August 2020
A North Carolina university experienced a rapid increase in COVID-19 cases and clusters within 2 weeks of opening the campus to students. Student gatherings and congregate living settings, both on and off campus, likely contributed to the rapid spread of COVID-19 in this setting.
During August 2–September 5, 2020, weekly COVID-19 cases among persons aged 18–22 years increased 55% nationally. Increases were greatest in the Northeast (144%) and Midwest (123%). Increases in cases were not solely attributable to increased testing.
Preventing and Responding to COVID-19 on College Campuses
The coronavirus disease 2019 (COVID-19) pandemic continues to present public health and societal challenges worldwide. Concerted public health efforts in the US at the local, state, territorial, national, and tribal levels remain paramount to protecting the population, particularly those at greatest risk for severe illness and death.
September 28, 2020
COVID-19 Trends Among School-Aged Children — United States, March 1–September 19, 2020
It is important for schools and communities to monitor multiple indicators of COVID-19 among school-aged children and layer prevention strategies to reduce COVID-19 disease risk for students, teachers, school staff, and families. These results can provide a baseline for monitoring trends and evaluating mitigation strategies.
COVID research updates: Tests reveal silent reinfections in hospital workers
Nature wades through the literature on the new coronavirus — and summarizes key papers as they appear.
September 25, 2020
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets multiple organs and causes severe coagulopathy. Histopathological organ changes might not only be attributable to a direct virus-induced effect, but also the immune response. The aims of this study were to assess the duration of viral presence, identify the extent of inflammatory response, and investigate the underlying cause of coagulopathy.
Many patients receiving dialysis in the USA share the socioeconomic characteristics of underserved communities, and undergo routine monthly laboratory testing, facilitating a practical, unbiased, and repeatable assessment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence.
September 24, 2020
Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection.
Gastrointestinal Complications in Critically Ill Patients With and Without COVID-19
Coronavirus disease 2019 (COVID-19) appears to have significant extrapulmonary complications affecting multiple organ systems. Critically ill patients with COVID-19 often develop gastrointestinal complications during their hospital stay, including bowel ischemia, transaminitis, gastrointestinal bleeding, pancreatitis, Ogilvie syndrome, and severe ileus.
September 23, 2020
As Their Numbers Grow, COVID-19 “Long Haulers” Stump Experts
Overall, approximately 10% of people who’ve had COVID-19 experience prolonged symptoms, a UK team estimated in a recently published Practice Pointer on postacute COVID-19 management. And yet, the authors wrote, primary care physicians have little evidence to guide their care.
Changing Age Distribution of the COVID-19 Pandemic — United States, May–August 2020
Strict adherence to community mitigation strategies and personal preventive behaviors by younger adults is needed to help reduce infection and subsequent transmission to persons at higher risk for severe illness.
Association of SARS-CoV-2 Test Status and Pregnancy Outcomes
Associations of coronavirus disease 2019 (COVID-19) and pregnancy outcomes remain unclear because most studies are case reports or case series without contemporary comparators.
September 22, 2020
COVID-19 Contact Tracing in Two Counties — North Carolina, June–July 2020
Despite aggressive efforts by health departments, many COVID-19 patients do not report contacts, and many contacts cannot be reached. Improved timeliness of contact tracing, community engagement, and community-wide mitigation are needed to reduce SARS-CoV-2 transmission.
September 21, 2020
Hydroxychloroquine is one of several agents being evaluated in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to examine whether patients with rheumatological conditions receiving chronic hydroxychloroquine therapy are at less risk of developing SARS-CoV-2 infection than those not receiving hydroxychloroquine.
September 18, 2020
Who gets a COVID vaccine first? Access plans are taking shape
Advisory groups around the world release guidance to prioritize health-care workers and those in front-line jobs.
Nonfatal Opioid Overdoses at an Urban Emergency Department During the COVID-19 Pandemic
Psychosocial consequences related to coronavirus disease 2019 (COVID-19) may place individuals at a heightened likelihood of opioid overdose or relapse.
The novel coronavirus disease 2019 (COVID-19) pandemic has exacerbated challenges for millions of adults with substance use disorders. New obstacles for obtaining treatment exist as do increasing stressors, including isolation, unemployment, and illness.
September 17, 2020
Covid-19: Do many people have pre-existing immunity?
It seemed a truth universally acknowledged that the human population had no pre-existing immunity to SARS-CoV-2, but is that actually the case?
Access to rapid diagnosis is key to the control and management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory RT-PCR testing is the current standard of care but usually requires a centralised laboratory and significant infrastructure. We describe our diagnostic accuracy assessment of a novel, rapid point-of-care real time RT-PCR CovidNudge test, which requires no laboratory handling or sample pre-processing.
Efforts to prevent COVID-19 led to global decline in flu
Interventions to prevent SARS-CoV-2 transmission have led to a global decline in influenza during the COVID-19 pandemic, researchers reported in MMWR.
Change in Antibodies to SARS-CoV-2 Over 60 Days Among Health Care Personnel in Nashville, Tennessee
Declines in immunoglobulin antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among patients with symptomatic or asymptomatic infections have been documented.
September 16, 2020
Detection of SARS-CoV-2 with SHERLOCK One-Pot Testing
CRISPR (clustered regularly interspaced short palindromic repeats)–based diagnostic tests1,2 collectively provide a nascent platform for the detection of viral and bacterial pathogens. Methods such as SHERLOCK (specific high-sensitivity enzymatic reporter unlocking), which typically use a two-step process (target amplification followed by CRISPR-mediated nucleic acid detection),1,2 have been used to detect SARS-CoV-2.3
Pregnant women and health care providers should be aware of potential risks for severe COVID-19, including adverse pregnancy outcomes. Identifying COVID-19 during birth hospitalizations is important to guide preventive measures to protect pregnant women, parents, newborns, other patients, and hospital personnel.
Antenatal counseling emphasizing preventive measures, including use of masks, frequent hand washing, and social distancing, might help prevent COVID-19 among pregnant women, especially those with prepregnancy obesity and gestational diabetes.
Occupational Safety and Health Administration (OSHA) and Worker Safety During the COVID-19 Pandemic
With the coronavirus disease 2019 (COVID-19) pandemic, the US is facing an unprecedented, massive worker safety crisis.
September 15, 2020
SARS-CoV-2–Associated Deaths Among Persons Aged >21 Years — United States, February 12–July 31, 2020
Since February 12, 2020, approximately 6.5 million cases of SARS-CoV-2 infection, the cause of coronavirus disease 2019 (COVID-19), and 190,000 SARS-CoV-2–associated deaths have been reported in the United States.
September 14, 2020
Seasonal coronavirus protective immunity is short-lasting
A key unsolved question in the current coronavirus disease 2019 (COVID-19) pandemic is the duration of acquired immunity. Insights from infections with the four seasonal human coronaviruses might reveal common characteristics applicable to all human coronaviruses. We monitored healthy individuals for more than 35 years and determined that reinfection with the same seasonal coronavirus occurred frequently at 12 months after infection.
The coronavirus disease 2019 (COVID-19) pandemic has challenged the adequacy of the blood supply. To attract new donors and support the collection of convalescent plasma,1 many blood collection organizations have implemented and publicized routine testing of donations for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies.
September 11, 2020
Findings from a case-control investigation of symptomatic outpatients from 11 U.S. health care facilities found that close contact with persons with known COVID-19 or going to locations that offer on-site eating and drinking options were associated with COVID-19 positivity. Adults with positive SARS-CoV-2 test results were approximately twice as likely to have reported dining at a restaurant than were those with negative SARS-CoV-2 test results.
Eating and drinking on-site at locations that offer such options might be important risk factors associated with SARS-CoV-2 infection. Efforts to reduce possible exposures where mask use and social distancing are difficult to maintain, such as when eating and drinking, should be considered to protect customers, employees, and communities.
September 10, 2020
Rapid Decay of Anti–SARS-CoV-2 Antibodies in Persons with Mild Covid-19
A recent article suggested the rapid decay of anti–SARS-CoV-2 IgG in early infection,1 but the rate was not described in detail. We evaluated persons who had recovered from Covid-19 and referred themselves to our institution for observational research.
The emergence of SARS-CoV-2 in Europe and North America
Our analyses demonstrate the effectiveness of public health measures in preventing onward transmission and show that intensive testing and contact tracing could have prevented SARS-CoV-2 from becoming established.
September 8, 2020
Prevalence of Third-Party Tracking on COVID-19–Related Web Pages
The internet provides ready access to information related to coronavirus disease 2019 (COVID-19). With a simple web search, individuals can find symptom checkers, locate testing sites, and get tips for keeping themselves safe.
September 3, 2020
Cytokine Levels in Critically Ill Patients With COVID-19 and Other Conditions
An abnormally strong proinflammatory response known as “cytokine storm” may play an important role in the pathophysiology of coronavirus disease 2019 (COVID-19), although cytokine storm remains ill defined.1 Sinha and colleagues2 reported that although IL-6 levels are elevated in severe COVID-19, they are lower than levels usually observed in (non–COVID-19) acute respiratory distress syndrome (ARDS). However, this comparison is limited by the use of different assays, which are not well standardized.3 We compared cytokine levels in critically ill patients with COVID-19 vs levels in patients with other critical illnesses.
September 2, 2020
Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine
NVX-CoV2373 is a recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant.
September 1, 2020
On August 23, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA)* for COVID-19 convalescent plasma for the treatment of hospitalized patients with COVID-19.
Humoral Immune Response to SARS-CoV-2 in Iceland
Little is known about the nature and durability of the humoral immune response to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The Power of Antibody-Based Surveillance
Antibodies are immune proteins that mark the evolution of the host immune response to infection. Antibodies can be measured in a sensitive and specific manner, providing an archive that reflects recent or previous infection. If maintained at sufficiently high levels, antibodies can rapidly block infection on reexposure, conferring long-lived protection.
Even octogenarians develop potent antibodies
As the new coronavirus ripped through several care homes in England, more than 80% of the residents mounted an antibody response to the virus, including 82% of those over the age of 80.
August 31, 2020
Among 3,248 personnel observed, 6% had antibody evidence of previous SARS-CoV-2 infection; 29% of personnel with SARS-CoV-2 antibodies were asymptomatic in the preceding months, and 69% had not previously received a diagnosis of SARS-CoV-2 infection. Prevalence of SARS-CoV-2 antibodies was lower among personnel who reported always wearing a face covering while caring for patients (6%), compared with those who did not (9%).
The effect of the coronavirus disease 2019 (COVID-19) pandemic on the primary care community health centers (CHCs) in the US has not been well described. CHCs serve approximately 30 million people, including high proportions of patients susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and adverse outcomes.
Emergency Use Authorizations During the COVID-19 Pandemic
In response to the novel coronavirus disease 2019 (COVID-19) crisis, the Food and Drug Administration (FDA), via its Emergency Use Authorization (EUA) authority, initially provided, and then revoked, authorization for use of hydroxychloroquine for treating patients with COVID-19. This process was politically and scientifically contentious and illustrates central problems that can arise with emergency drug authorizations during crises.
August 29, 2020
Research and higher education in the time of COVID-19
The COVID-19 pandemic has propelled the research and higher education sectors to the forefront of public attention. Laboratory capacity has been crucial for diagnostic testing; experts in infectious diseases, epidemiology, public health, mathematical modelling, and economics are central to national policy making and media coverage; clinical research has been vital to improving COVID-19 management; and our collective global future relies heavily on the development of an effective vaccine against severe acute respiratory syndrome coronavirus 2.
August 28, 2020
Testing for responses to the wrong SARS-CoV-2 antigen?
Two commercial antibody tests (Abbott SARS-CoV-2 IgG, Abbott Diagnostics, Abbott Park, IL, USA; and Roche Elecsys Anti-SARS-CoV-2, Roche Diagnostics, Basel, Switzerland), both targeting antibodies to nucleoprotein (anti-NP), constitute the cornerstone of the UK Government's response to the COVID-19 pandemic.
Saliva or Nasopharyngeal Swab Specimens for Detection of SARS-CoV-2
Rapid and accurate diagnostic tests are essential for controlling the ongoing Covid-19 pandemic. Although the current standard involves testing of nasopharyngeal swab specimens by quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) to detect SARS-CoV-2, saliva specimens may be an alternative diagnostic sample.
Salivary Detection of COVID-19
Standard testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires a nasopharyngeal or oropharyngeal swab but is limited by modest sensitivity, the need for health care human resources and personal protective equipment, and the potential for transmission in transit to or at the testing center.
August 27, 2020
Patients with COVID-19-associated ARDS have a form of injury that, in many aspects, is similar to that of those with ARDS unrelated to COVID-19. Notably, patients with COVID-19-related ARDS who have a reduction in respiratory system compliance together with increased D-dimer concentrations have high mortality rates.
In this exploratory analysis of 39 patients, ARDS due to COVID-19 was not associated with higher systemic inflammation and was associated with a lower prevalence of the hyperinflammatory phenotype than that observed in historical ARDS data. This finding suggests that the excess mortality observed in COVID-19-related ARDS is unlikely to be due to the upregulation of inflammatory pathways described by the parsimonious model.
Covid-19 and Immunity in Aging Populations — A New Research Agenda
The race is on throughout the world to develop Covid-19 vaccines and therapeutics and end a pandemic that threatens to infect a substantial portion of the planet’s population and perhaps kill millions of people, especially older adults.
August 26, 2020
Developing Safe and Effective Covid Vaccines — Operation Warp Speed’s Strategy and Approach
Announced on May 15, Operation Warp Speed (OWS) — a partnership of the Department of Health and Human Services (HHS), the Department of Defense (DOD), and the private sector — aims to accelerate control of the Covid-19 pandemic by advancing development, manufacturing, and distribution of vaccines, therapeutics, and diagnostics.
Preventing and Mitigating SARS-CoV-2 Transmission — Four Overnight Camps, Maine, June–August 2020
During the 2020 summer camp season, four Maine overnight camps with 1,022 attendees from 41 states and international locations implemented a multilayered prevention and mitigation strategy that was successful in identifying and isolating three asymptomatic COVID-19 cases and preventing secondary transmission.
The Transformational Effects of COVID-19 on Medical Education
In 2010, a Global Independent Commission on Education of Health Professionals for the 21st Century, composed of experts in public health and health care from around the world, asserted that the purpose of health professions education was to improve the health of communities.
August 25, 2020
Two metres or one: what is the evidence for physical distancing in covid-19?
Rigid safe distancing rules are an oversimplification based on outdated science and experiences of past viruses, argue Nicholas R Jones and colleagues
State and local health departments in other jurisdictions might benefit from implementation of systematic indicator monitoring to guide decision-making for COVID-19 reopening, mitigation, and response efforts.
August 24, 2020
First Case of COVID-19 Reinfection Confirmed
The man was diagnosed with COVID-19 on March 26, hospitalized, then recovered. He tested positive for SARS-CoV-2 again on August 15, and whole genome sequencing of viral isolates from the two episodes indicated they were from different clades, reported Kwok-Yung Yuen, MD, of the University of Hong Kong, and colleagues in a manuscript they said had been accepted for publication in Clinical Infectious Diseases, but not yet published.
August 22, 2020
Unraveling the Immune Response in Severe COVID-19
An outbreak of coronavirus disease 2019 (COVID-19) emerged in China’s Hubei province and spread rapidly across the globe leading to millions of cases worldwide. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel enveloped RNA-virus of the family of beta-coronavirus, was quickly identified and sequences distributed, initiating a race to develop vaccines and therapeutics that is unprecedented in history.
Convergence between global BCG vaccination and COVID‐19 pandemic
The novel coronavirus SARS‐CoV‐2 has kept the whole world in tenterhooks due to its severe life‐threatening infectious disease, COVID‐19.
Various mental health interventions have been developed for medical pandemics, and research on their effectiveness is growing.
Fuzzy Clustering method to Compare the Spread Rate of Covid-19 in the High Risks Countries
The numbers of confirmed cases of new coronavirus (Covid-19) are increased daily in different countries. To determine the policies and plans, the study of the relations between the distributions of the spread of this virus in other countries is critical. In this work, the distributions of the spread of Covid-19 in Unites States America, Spain, Italy, Germany, United Kingdom, France, and Iran were compared and clustered using fuzzy clustering technique.
August 19, 2020
A SARS-CoV-2 mRNA Vaccine — Preliminary Report
The authors reply: We agree with Schachar and Schachar that the interim findings of the phase 1 trial of the mRNA-1273 vaccine against SARS-CoV-2 are promising; these findings provided support for the initiation of the phase 2 and 3 trials that are under way.
COVID-19 Among American Indian and Alaska Native Persons — 23 States, January 31–July 3, 2020
Adequate health care and public health infrastructure resources are needed to support a culturally responsive public health effort that sustains the strengths of AI/AN communities. These resources would facilitate the collection and reporting of more complete case report data to support evidence-based public health efforts.
August 17, 2020
During March 6–June 5, 2020, workplace outbreaks occurred in 15 Utah industry sectors; 58% of workplace outbreak-associated COVID-19 cases were in three sectors: Manufacturing, Wholesale Trade, and Construction. Despite representing 24% of Utah workers in all affected sectors, Hispanic and nonwhite workers accounted for 73% of workplace outbreak-associated COVID-19 cases.
SARS-CoV-2 Infection Among Community Health Workers in India Before and After Use of Face Shields
The transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to be predominantly through respiratory droplets from infected persons in close proximity to uninfected persons,1 although airborne transmission may also play a role.2,3 Face shields have been proposed to prevent transmission in the community,4 but data are lacking. We describe transmission in a community setting before and after the use of face shields.
August 15, 2020
Neck gaiters provide similar performance to other cloth masks we have tested on manikins.
August 14, 2020
Tocilizumab, a monoclonal antibody directed against the interleukin-6 receptor, has been proposed to mitigate the cytokine storm syndrome associated with severe COVID-19. We aimed to investigate the association between tocilizumab exposure and hospital-related mortality among patients requiring intensive care unit (ICU) support for COVID-19.
Among 79 counties identified as hotspots during June 5–18, 2020 that also had sufficient data on race, a disproportionate number of COVID-19 cases among underrepresented racial/ethnic groups occurred in almost all areas during February–June 2020.
During June 24–30, 2020, U.S. adults reported considerably elevated adverse mental health conditions associated with COVID-19. Younger adults, racial/ethnic minorities, essential workers, and unpaid adult caregivers reported having experienced disproportionately worse mental health outcomes, increased substance use, and elevated suicidal ideation.
August 13, 2020
Texas is experiencing resurgence of coronavirus disease 2019 (COVID-19). We report sociodemographic, clinical, and outcome differences across the first and second surges of COVID-19 hospitalizations at Houston Methodist, an 8-hospital health care system in Houston, Texas.
Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes
This inactivated COVID-19 vaccine had a low rate of adverse reactions and demonstrated immunogenicity, but longer-term assessment of safety and efficacy will require phase 3 trials.
Caring for Someone With COVID-19
Care of individuals with COVID-19 is 2-fold: support the patient and prevent yourself and others from contracting SARS-CoV-2.
August 11, 2020
Investigation of a COVID-19 outbreak in a Maryland nursing home identified a significantly higher prevalence among residents receiving dialysis (47%) than among those not receiving dialysis (16%); 72% were asymptomatic at the time of testing.
Facility-Wide Testing for SARS-CoV-2 in Nursing Homes — Seven U.S. Jurisdictions, March–June 2020
In two health department jurisdictions, testing in facilities without a previous COVID-19 case identified a prevalence of 0.4%. Five health department jurisdictions that targeted facility-wide testing after identification of a case found a prevalence of 12%; for each additional day before completion of initial facility-wide testing, an estimated 1.3 additional cases were identified.
August 10, 2020
In the US, approximately 27% of deaths due to coronavirus disease 2019 (COVID-19) have occurred among residents of nursing homes (NHs).1 However, why some facilities have been more successful at limiting the spread of infection than others is unclear. For example, those with greater staffing or higher performance on quality measures may be better at containing the spread of COVID-19 among staff and residents.
As of July 13, 2020, Canada has documented 107 861 cases of coronavirus disease 2019 (COVID-19) (286 per 100 000 people) and 8787 COVID-19–related deaths.
August 7, 2020
Low-cost measurement of facemask efficacy for filtering expelled droplets during speech
Mandates for mask use in public during the recent COVID-19 pandemic, worsened by global shortage of commercial supplies, have led to widespread use of homemade masks and mask alternatives. It is assumed that wearing such masks reduces the likelihood for an infected person to spread the disease, but many of these mask designs have not been tested in practice. We have demonstrated a simple optical measurement method to evaluate the efficacy of masks to reduce the transmission of respiratory droplets during regular speech. In proof-of-principle studies, we compared a variety of commonly available mask types and observed that some mask types approach the performance of standard surgical masks, while some mask alternatives, such as neck fleece or bandanas, offer very little protection.
COVID-19–Associated Multisystem Inflammatory Syndrome in Children — United States, March–July 2020
Most cases of MIS-C have features of shock, with cardiac involvement, gastrointestinal symptoms, and significantly elevated markers of inflammation, with positive laboratory test results for SARS-CoV-2. Of the 565 patients who underwent SARS-CoV-2 testing, all had a positive test result by RT-PCR or serology.
Analysis of pediatric COVID-19 hospitalization data from 14 states found that although the cumulative rate of COVID-19–associated hospitalization among children (8.0 per 100,000 population) is low compared with that in adults (164.5), one in three hospitalized children was admitted to an intensive care unit.
Low-cost measurement of facemask efficacy for filtering expelled droplets during speech
Mandates for mask use in public during the recent COVID-19 pandemic, worsened by global shortage of commercial supplies, have led to widespread use of homemade masks and mask alternatives. It is assumed that wearing such masks reduces the likelihood for an infected person to spread the disease, but many of these mask designs have not been tested in practice.
Allocation of COVID-19 Relief Funding to Disproportionately Black Counties
The Coronavirus Aid, Relief, and Economic Security (CARES) Act and Paycheck Protection Program together designated $175 billion for coronavirus disease 2019 (COVID-19) response efforts and reimbursement to health care entities for expenses or lost revenues.
In this cross-sectional study of 15 244 hospitalizations involving 14 724 patients with AMI, case rates began to decrease on February 23, 2020, followed by a modest recovery after 5 weeks. Although no statistically significant difference in treatment approaches was found, the risk-adjusted mortality rate among patients with ST-segment elevation myocardial infarction increased substantially.
COVID-19 Outbreak Among Employees at a Meat Processing Facility — South Dakota, March–April 2020
Implementing control measures before, or soon after, SARS-CoV-2 introduction into meat processing facilities, especially in areas where employees have prolonged, close contact with others, might substantially reduce the risk for SARS-CoV-2 spread within facilities.
August 6, 2020
Perspectives on Oncology-Specific Language During the Coronavirus Disease 2019 Pandemic
In this qualitative study of 8 physicians and 48 patients with cancer, the physicians identified 8 oncology-specific scenarios in which communication with patients had been challenging, and the patients provided their reactions to each scenario. These physician and patient insights, along with principles identified through literature review by health communication experts, were synthesized for application to the clinical scenarios.
Prevalence of SARS-CoV-2 Antibodies in Health Care Personnel in the New York City Area
The greater New York City (NYC) area, including the 5 boroughs and surrounding counties, has a high incidence of coronavirus disease 2019 (COVID-19),1 and health care personnel (HCP) working there have a high exposure risk. HCP have expressed concerns about access to testing so that infection spread to patients, other HCP, and their families can be minimized.2 The Northwell Health System, the largest in New York State, sought to address this concern by offering voluntary antibody testing to all HCP.
August 5, 2020
Experts Discuss COVID-19—Remdesivir, Vaccines, and More
JAMA Live Highlights features comments from livestream interviews by JAMA Network Editor in Chief Howard Bauchner, MD. His discussions with experts in clinical care, public health, and health policy focus on critical issues related to the coronavirus disease 2019 (COVID-19) pandemic. Comments have been edited for clarity.
Livedoid and Purpuric Skin Eruptions Associated With Coagulopathy in Severe COVID-19
As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection spreads globally, dermatologists are recognizing a variety of cutaneous manifestations in patients with coronavirus disease 2019 (COVID-19). A recent Spanish report1 categorized skin findings in 375 patients with suspected and confirmed COVID-19, including livedoid and necrotic eruptions, which were noted in patients with more severe disease. The authors suggested that these skin manifestations may be associated with occlusive vascular disease.
In this cross-sectional study of 60 US ophthalmology practices, there were fairly uniform responses to 3 common ocular complaints across comprehensive ophthalmological practices. Private practices were more likely to schedule cataract evaluations and patients with posterior vitreous detachments sooner than university centers, while all practices were likely to ask about COVID-19 symptoms when scheduling urgent visits.
Alcohol-based hand sanitizer products should never be ingested. In patients with compatible signs and symptoms or after having swallowed hand sanitizer, prompt evaluation for methanol poisoning is required. Health departments in all states should coordinate with poison centers to identify cases of methanol poisoning.
Attacks on Public Health Officials During COVID-19
On June 24, 2020, California Governor Gavin Newsom remarked on a disturbing phenomenon: health officers are “getting attacked, getting death threats, they’re being demeaned and demoralized.”
As of July 30, 2020, more than 17 million people worldwide have been diagnosed with coronavirus disease 2019 (COVID-19), and more than 665 000 have died. In many countries, the rate of diagnosis continues to increase; for example, more than 50 000 new cases per day were reported in the US during the last week of July.
August 3, 2020
Maine found that using automated symptom monitoring as a part of the state’s contact tracing program was well received, with the majority of monitored contacts (96.4%) agreeing to automated symptom monitoring. Automated symptom monitoring promptly identified COVID-19 diagnoses among monitored contacts. Among 1,622 persons enrolled into an automated symptom monitoring system, 190 (11.7%) developed COVID-19.
July 31, 2020
SARS-CoV-2 Transmission and Infection Among Attendees of an Overnight Camp — Georgia, June 2020
Limited data are available about transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), among youths. During June 17–20, an overnight camp in Georgia (camp A) held orientation for 138 trainees and 120 staff members; staff members remained for the first camp session, scheduled during June 21–27, and were joined by 363 campers and three senior staff members on June 21.
In this modeling study, symptom-based screening alone was not sufficient to contain an outbreak, and the safe reopening of campuses in fall 2020 may require screening every 2 days, uncompromising vigilance, and continuous attention to good prevention practices.
July 30, 2020
Our analyses suggest children younger than 5 years with mild to moderate COVID-19 have high amounts of SARS-CoV-2 viral RNA in their nasopharynx compared with older children and adults. Our study is limited to detection of viral nucleic acid, rather than infectious virus, although SARS-CoV-2 pediatric studies reported a correlation between higher nucleic acid levels and the ability to culture infectious virus. Thus, young children can potentially be important drivers of SARS-CoV-2 spread in the general population, as has been demonstrated with respiratory syncytial virus, where children with high viral loads are more likely to transmit.
A widely publicized press release and subsequent preliminary report of the RECOVERY trial, a randomized study conducted in the UK, noted a survival benefit with the use of dexamethasone in hospitalized patients with coronavirus disease 2019 (COVID-19).1 The use of dexamethasone for management of COVID-19 has already increased, particularly given the recent National Institutes of Health COVID-19 Treatment Panel guidelines that recommend its use.
July 29, 2020
Association Between Statewide School Closure and COVID-19 Incidence and Mortality in the US
There was a temporal association between statewide school closure and lower COVID-19 incidence and mortality, although some of the reductions may have been related to other concurrent nonpharmaceutical interventions.
The coronavirus disease 2019 (COVID-19) pandemic has presented unprecedented challenges to the nation’s kindergarten-grade 12 education system. The rush to respond to the pandemic led to closures of school buildings across the country, with little time to ensure continuity of instruction or to create a framework for deciding when and how to reopen schools. States and school districts are now grappling with the complex questions of whether and how to reopen school buildings in the context of rapidly changing patterns of community spread.
Comparison of Face-Touching Behaviors Before and During the Coronavirus Disease 2019 Pandemic
These findings suggest that mandatory mask-wearing policies were associated with reducing face-touching behavior among the general population in public areas, which may help to prevent contact transmission of COVID-19.
Reopening Primary Schools during the Pandemic
For the past 6 months, policymakers and the U.S. public have weighed economic against public health considerations in debating what limits to set on individual and collective behaviors in attempting to control the Covid-19 pandemic. As fall approaches, attention has turned to a third pillar of a pandemic-resilient society: schools.
Public Health Decision Making during Covid-19 — Fulfilling the CDC Pledge to the American People
In May 2020, the Centers for Disease Control and Prevention (CDC) released considerations for the opening of elementary and high schools. opens in new tab in the fall in light of the Covid-19 pandemic. The agency also developed a decision tool. opens in new tab to guide school systems in deciding when schools should be opened and a 9-page checklist. opens in new tab for school administrators with policies and procedures, facilities and supplies, and education and training needed for safe reopening of schools.
July 28, 2020
Surveillance and mortality data show large inequities in the impact of coronavirus disease 2019 (COVID-19) by race/ethnicity. Currently, the US Centers for Disease Control and Prevention (CDC) does not report mortality rates by race/ethnicity. Instead, the percentage distribution of COVID-19 deaths by race/ethnicity is presented alongside a weighted distribution of the population from the CDC’s National Center for Health Statistics, which weights each county’s population by its share of COVID-19 deaths, not population.
While the excess burden of both infections and deaths was experienced by poorer and more diverse areas, racial and ethnic disparities in COVID-19 infections and deaths existed beyond those explained by differences in income. Lack of access to disaggregated data precludes us from further exploring causal mechanisms, such as structural racism or other social drivers. Studies that leverage community information with individual-level health data are likely to provide additional insights.
July 27,2020
Characteristics and Strength of Evidence of COVID-19 Studies Registered on ClinicalTrials.gov
The coronavirus disease 2019 (COVID-19) pandemic has led to a massive activation of clinical research. The methodological strength of these studies is not well characterized but has implications for the quality of evidence produced. We evaluated the characteristics and expected strength of evidence of COVID-19 studies registered on ClinicalTrials.gov.
Illness-Related Work Absence in Mid-April Was Highest on Record
Our findings shed light on the combined health and economic effects of the COVID-19 pandemic, particularly for immigrant, older, and less-educated workers. Finally, our study suggests that routinely collected CPS data on work absence may provide a rapidly available tool for surveillance of the effect of public health crises on the workforce.
These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.
In this mathematical modeling study, breathing and coughing by a simulated individual with COVID-19 were estimated to release large numbers of viruses in a poorly ventilated room with a coughing person. However, the estimated infectious risk posed by a person with typical viral load who breathes normally was low, and only few people with very high viral load posed an infection risk in a poorly ventilated closed environment.
Asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to be a major public health concern. Health care workers (HCWs) are at higher risk of infection and can become inadvertent vehicles of transmission. Therefore, Houston Methodist initiated a coronavirus disease 2019 (COVID-19) surveillance program among asymptomatic HCWs and expanded to asymptomatic community residents. We report prevalence of SARS-CoV-2 among the first group tested.
July 26, 2020
Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates
Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates.
July 24, 2020
The median model-based estimate of the prevalence of any of five underlying medical conditions associated with increased risk for severe COVID-19–associated illness among U.S. adults was 47.2% among 3,142 U.S. counties. The estimated number of persons with these conditions followed population distributions, but prevalence was higher in more rural counties.
The number of reported cases represents an estimated one of 10 infections. Given that many persons in Indiana remain susceptible, adherence to evidence-based public health mitigation measures (e.g., social distancing, consistent and correct use of face coverings, and hand hygiene) is needed to reduce surge in hospitalizations and prevent morbidity and mortality from COVID-19.
Serologic surveillance can complement case-based and syndromic surveillance. At the time of this survey, most of the two-county population had not been previously infected with SARS-CoV-2, highlighting the importance of continued mitigation measures to prevent infection, including social distancing, consistent and correct use of face coverings, and hand hygiene.
In a multistate telephone survey of symptomatic adults who had a positive outpatient test result for SARS-CoV-2 infection, 35% had not returned to their usual state of health when interviewed 2–3 weeks after testing. Among persons aged 18–34 years with no chronic medical conditions, one in five had not returned to their usual state of health.
Presence of Genetic Variants Among Young Men With Severe COVID-19
In a case series that included 4 young male patients with severe COVID-19 from 2 families, rare loss-of-function variants of the X-chromosomal TLR7 were identified, with immunological defects in type I and II interferon production.
July 23, 2020
Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19
Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited.
July 22, 2020
Rapid Scaling Up of Covid-19 Diagnostic Testing in the United States — The NIH RADx Initiative
The first reports of an unusual cluster of pneumonia cases in the city of Wuhan, China, emerged in December 2019, heralding a global pandemic. As of July 13, 2020, more than 3.3 million U.S. residents have received a diagnosis of coronavirus disease 2019 (Covid-19), and more than 135,000 have died.
Pooling Data From Individual Clinical Trials in the COVID-19 Era
The rapid pace of the coronavirus disease 2019 (COVID-19) pandemic caused many research efforts to be initiated quickly. In some cases, nationally based platform trials have begun to report results.1 More frequently, however, randomized clinical trials (RCTs) were launched in local settings and in several cases missed the peak of the pandemic in their region.
The Advisory Committee on Immunization Practices and Its Role in the Pandemic Vaccine Response
More than 3.7 million infections and more than 140 000 deaths due to coronavirus disease 2019 (COVID-19) have occurred in the US in the past 6 months. As case counts continue to increase, robust vaccine development efforts unprecedented in scale and speed are being pursued.
July 21, 2020
Rapid Decay of Anti–SARS-CoV-2 Antibodies in Persons with Mild Covid-19
A recent article suggested the rapid decay of anti–SARS-CoV-2 IgG in early infection,1 but the rate was not described in detail. We evaluated persons who had recovered from Covid-19 and referred themselves to our institution for observational research. Written informed consent was obtained from all the participants, with approval by the institutional review board.
Seroprevalence of Antibodies to SARS-CoV-2 in 10 Sites in the United States, March 23-May 12, 2020
For most sites, it is likely that greater than 10 times more SARS-CoV-2 infections occurred than the number of reported COVID-19 cases; most persons in each site, however, likely had no detectable SARS-CoV-2 antibodies.
In a random sample of Indiana residents aged ≥12 years, the estimated prevalence of current or previous SARS-CoV-2 infection in late April 2020 was 2.79%. Among persons with active infection, 44% reported no symptoms.
A community seroprevalence survey, conducted in two counties in metropolitan Atlanta during April 28–May 3, using a two-stage cluster sampling design and serologic testing, estimated that 2.5% of the population had antibodies to SARS-CoV-2.
Autopsies reveal surprising cardiac changes in COVID-19 patients
A series of autopsies conducted by LSU Health New Orleans pathologists shows the damage to the hearts of COVID-19 patients is not the expected typical inflammation of the heart muscle associated with myocarditis, but rather a unique pattern of cell death in scattered individual heart muscle cells.
COVID-19 patient autopsies reveal surprising results in LSU
“We identified key gross and microscopic changes that challenge the notion that typical myocarditis is present in severe SARS-CoV-2 infection,” says Dr. Richard Vander Heide, Professor and Director of Pathology Research at LSU Health New Orleans School of Medicine. “While the mechanism of cardiac injury in COVID-19 is unknown, we propose several theories that bear further investigation that will lead to greater understanding and potential treatment interventions.”
Autopsies by LSU Health pathologists show surprising cardiac changes in COVID-19 patients
A series of autopsies conducted by LSU Health New Orleans pathologists shows the damage to the hearts of COVID-19 patients is not the expected typical inflammation of the heart muscle associated with myocarditis, but rather a unique pattern of cell death in scattered individual heart muscle cells.
July 20, 2020
Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System
Patients with coronavirus disease 2019 (COVID-19) are at increased risk of thrombosis.1 However, studies have been limited in size, did not report all thrombotic events, and focused on patients with severe disease hospitalized in intensive care units (ICUs). We assessed the incidence of, and risk factors for, venous and arterial thrombotic events in all hospitalized patients with COVID-19 at a large health system consisting of 4 hospitals in New York City.
During the coronavirus disease 2019 (COVID-19) pandemic, a significantly lower rate of health care use has been reported, potentially leading to delayed medical care. Diabetic ketoacidosis is an acute life-threatening complication of a delayed diagnosis of type 1 diabetes.
July 17, 2020
Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report
In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (
Research in the Context of a Pandemic
The current literature on the treatment of coronavirus disease 2019 (Covid-19) is filled with anecdotal reports of therapeutic successes in clinical trials with small numbers of patients and observational cohort studies claiming efficacy with little regard to the effect of unrecognized confounders. For the field to move forward and for patients’ outcomes to improve, there will need to be fewer small or inconclusive studies and more studies such as the dexamethasone trial now reported by the RECOVERY Collaborative Group in the Journal.
July 16, 2020
When the dread starts to set in, when it gets hard to breathe, I adjust my N95 mask and remind myself of this: I am the granddaughter of a man who worked the depths of Idaho mines and knew a thing or two about personal protective equipment (PPE) hell.
July 15, 2020
What Is the Burden of Excess Deaths Due to COVID-19 in the U.S.?
Estimating excess deaths suggests that mortality related to COVID-19 has been undercounted.
Hydroxychloroquine as Postexposure Prophylaxis for Covid-19
The window for postexposure prophylaxis against Covid-19 is narrow. Therapy that is initiated up to 4 days after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is early treatment, not postexposure prophylaxis. The trial described in the article by Boulware et al. (published online on June 3 at NEJM.org) was therefore largely about the prevention of symptoms in persons who may already have been infected.
July 14, 2020
Risk Factors for Death from COVID-19 in a Cohort of 17 Million People
Those more likely to die with COVID-19 were older, male, had various medical conditions and socioeconomic deprivation, and — disturbingly — were members of a racial or ethnic minority.
Studies Show Importance of Face Coverings in Limiting Spread of COVID-19
A trio of studies takes a closer look at face mask use in the U.S.
Universal Masking to Prevent SARS-CoV-2 Transmission—The Time Is Now
In this issue of JAMA, Wang et al present evidence that universal masking of health care workers (HCWs) and patients can help reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.1 In the largest health care system in Massachusetts with more than 75 000 employees, in tandem with routine symptom screening and diagnostic testing of symptomatic HCWs for SARS-CoV-2 infection, leadership mandated a policy of universal masking for all HCWs as well as for all patients.
An mRNA Vaccine against SARS-CoV-2 — Preliminary Report
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein.
The Covid-19 Vaccine-Development Multiverse
Leaving in its wake more than 12 million infections, over 550,000 deaths, and an economic toll in the trillions of dollars to date, the SARS-CoV-2 pandemic has devastated the most vulnerable in our society — adults 65 years of age or older, persons with underlying conditions, and the economically deprived. A vaccine is urgently needed to prevent Covid-19 and thereby stem complications and deaths resulting from transmission of the disease.
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has severely affected health care workers (HCWs). As a result, hospital systems began testing HCWs and implementing infection control measures to mitigate workforce depletion and prevent disease spread.
Evidence-Based Practice for Public Health Emergency Preparedness and Response
The coronavirus disease 2019 (COVID-19) pandemic has brought national attention to the importance of the work of state, local, tribal, and territorial public health agencies in protecting and securing the nation’s health. These agencies are routinely making difficult decisions about how to respond effectively to COVID-19, such as implementing nonpharmaceutical interventions and addressing the needs of at-risk populations.
As stay-at-home orders are lifted, professional and social interactions in the community will present more opportunities for spread of SARS-CoV-2. Broader implementation of face covering policies could mitigate the spread of infection in the general population.
Public health messages should target audiences not wearing cloth face coverings and reinforce positive attitudes, perceived norms, personal agency, and physical and health benefits of obtaining and wearing cloth face coverings consistently and correctly.
July 13, 2020
Critical Insights from Patients during the Covid-19 Pandemic
As health care systems look to resume normal operations during the Covid-19 pandemic, we must understand why patients are concerned about seeking care. This understanding will help guide strategies to ensure patient safety. In a survey of more than 1,300 patients at Vanderbilt University Medical Center, they said their biggest fear in returning to routine health care is the risk of getting sick from other patients.
A Mutation in SARS-CoV-2 Spike Protein Is Associated with Increased Infectivity
Virus with a spike protein variant, G614, spread rapidly worldwide and reached higher titers than virus with the original D614 protein.
Airborne Transmission of SARS-CoV-2
The coronavirus disease 2019 (COVID-19) pandemic has reawakened the long-standing debate about the extent to which common respiratory viruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are transmitted via respiratory droplets vs aerosols.
Communicating Science in the Time of a Pandemic
During the global SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, disseminating study findings (such as by preprints, news releases, news stories, or social media) and publishing the results of studies of testing and treatment in scientific journals increased quickly. As of July 6, a PubMed search for COVID-19 yielded almost 30 000 reports.
July 9, 2020
Audio Interview: Acute Lung Injury in Covid-19
The continuing spread of SARS-CoV-2 remains a Public Health Emergency of International Concern. What physicians need to know about transmission, diagnosis, and treatment of Covid-19 is the subject of ongoing updates from infectious disease experts at the Journal.
Persistent Symptoms in Patients After Acute COVID-19
In Italy, a large proportion of patients with coronavirus disease 2019 (COVID-19) presented with symptoms (71.4% of 31 845 confirmed cases as of June 3, 2020).1 Common symptoms include cough, fever, dyspnea, musculoskeletal symptoms (myalgia, joint pain, fatigue), gastrointestinal symptoms, and anosmia/dysgeusia.2-4 However, information is lacking on symptoms that persist after recovery. We assessed persistent symptoms in patients who were discharged from the hospital after recovery from COVID-19.
July 8, 2020
The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings
Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders.
Challenges Estimating Total Lives Lost in COVID-19 Decisions
The coronavirus disease 2019 (COVID-19) pandemic has claimed hundreds of thousands of lives, directly and indirectly, and threatens to claim many more. Nations have made different policy decisions that have affected the rate of infection, mortality, the economy, and the life of the country differently.
July 7, 2020
Targeted workplace interventions and prevention efforts that are appropriately tailored to the groups most affected by COVID-19 are critical to reducing both COVID-19–associated occupational risk and health disparities among vulnerable populations.
July 6, 2020
The Disproportionate Impact of Covid-19 on Communities of Color
Racism, cultural mistrust, miscommunication, chronic illness bred by limited food and living choices, and lived experience bind together communities of color as disparate as the Navajo Nation and Chelsea, Massachusetts. Why are we surprised? Because we are complacent.
On the Resources for the Public Page, at the top of the left column:
Today, Gov. John Bel Edwards announced a mandatory mask requirement for Louisiana and ordered bars in the state closed to on-premises consumption, as the state experiences increasing spread of COVID-19. The Governor also limited indoor social gatherings like wedding receptions, class reunions and parties to 50 total people. With these additional restrictions, Louisiana remains in Phase Two of the Roadmap for a Resilient Louisiana.
On the Resources for LSU Health New Orleans Page, at the top of the left column:
Today, Gov. John Bel Edwards announced a mandatory mask requirement for Louisiana and ordered bars in the state closed to on-premises consumption, as the state experiences increasing spread of COVID-19. The Governor also limited indoor social gatherings like wedding receptions, class reunions and parties to 50 total people. With these additional restrictions, Louisiana remains in Phase Two of the Roadmap for a Resilient Louisiana.
Spain is one of the European countries most affected by the COVID-19 pandemic. Serological surveys are a valuable tool to assess the extent of the epidemic, given the existence of asymptomatic cases and little access to diagnostic tests. This nationwide population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in Spain at national and regional level.
It is Time to Address Airborne Transmission of COVID-19
We appeal to the medical community and to the relevant national and international bodies to recognize the potential for airborne spread of COVID-19. There is significant potential for inhalation exposure to viruses in microscopic respiratory droplets (microdroplets) at short to medium distances (up to several meters, or room scale), and we are advocating for the use of preventive measures to mitigate this route of airborne transmission.
Developing a SARS-CoV-2 Vaccine at Warp Speed
With this background, the US Department of Health and Human Services (HHS) launched Operation Warp Speed—a partnership between government and industry—with the goal of delivering 300 million doses of a safe and effective vaccine by January 2021.3 This ambitious plan initially focused on 125 potential vaccine candidates, but was rapidly narrowed to 14 candidates in May 2020, and, as reported in June 2020, the current administration plans to narrow this list to 5 core candidates.
The Development of COVID-19 Vaccines
A safe and effective vaccine against coronavirus disease 2019 (COVID-19) is the best way to control and ultimately end the pandemic. Vaccine development is moving at unprecedented speed, with more than 200 candidates, billions of dollars committed, and manufacturing often proceeding before even knowing whether a given vaccine candidate will succeed.
June 30, 2020
Case investigation, contact tracing, and isolation of infected persons are needed to prevent ongoing community transmission, given the frequent lack of a known contact. Enhanced measures to ensure workplace safety, including social distancing and more widespread use of cloth face coverings, are warranted.
Finding Antibodies that Neutralize SARS-CoV-2
It’s now clear that nearly everyone who recovers from coronavirus disease 2019 (COVID-19) produces antibodies that specifically target SARS-CoV-2, the novel coronavirus that causes the infection. Yet many critical questions remain. A major one is: just how well do those particular antibodies neutralize the virus to fight off the infection and help someone recover from COVID-19? Fortunately, most people get better—but should the typical antibody response take the credit?
June 29, 2020
Early detection and isolation of persons with COVID-19, along with testing of close contacts, can slow the transmission of SARS-CoV-2 in correctional and detention facilities. Serial testing, particularly for close contacts of patients, is important for complete identification of cases and prompt public health response in congregate settings.
Multisystem Inflammatory Syndrome in U.S. Children and Adolescents
Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.)
Multisystem Inflammatory Syndrome in Children in New York State
The emergence of multisystem inflammatory syndrome in children in New York State coincided with widespread SARS-CoV-2 transmission; this hyperinflammatory syndrome with dermatologic, mucocutaneous, and gastrointestinal manifestations was associated with cardiac dysfunction.
Childhood Multisystem Inflammatory Syndrome — A New Challenge in the Pandemic
The recognition and description of new diseases often resemble the parable of the blind men and the elephant, with each declaring that the part of the beast they have touched fully defines it. As the coronavirus disease 2019 (Covid-19) pandemic has evolved, case reports have appeared describing children with unusual febrile illnesses that have features of Kawasaki’s disease, toxic shock syndrome, acute abdominal conditions, and encephalopathy, along with other reports of children with fever, elevated inflammatory markers, and multisystem involvement. It is now apparent that these reports were describing different clinical presentations of a new childhood inflammatory disorder.
Cognitive Bias and Public Health Policy During the COVID-19 Pandemic
As the coronavirus disease 2019 (COVID-19) pandemic abates in many countries worldwide, and a new normal phase arrives, critically assessing policy responses to this public health crisis may promote better preparedness for the next wave or the next pandemic. A key lesson is revealed by one of the earliest and most sizeable US federal responses to the pandemic: the investment of $3 billion to build more ventilators. These extra ventilators, even had they been needed, would likely have done little to improve population survival because of the high mortality among patients with COVID-19 who require mechanical ventilation and diversion of clinicians away from more health-promoting endeavors.
Taking a Closer Look at COVID-19, Health Inequities, and Racism
Meanwhile, the COVID-19 crisis also revealed the nation’s eroding public health readiness, according to Murray, an adjunct assistant professor at the University of Illinois at Chicago School of Public Health and a past president of the American Public Health Association.
June 26, 2020
Infectability of human BrainSphere neurons suggests neurotropism of SARS-CoV-2
Reports from Wuhan suggest that 36% of COVID-19 patients show neurological symptoms, and cases of viral encephalitis have been reported, suggesting that the virus is neurotropic under unknown circumstances. This is well established for other coronaviruses.
Editorial Evaluation and Peer Review During a Pandemic
Concerns have been raised about how journals maintain their standards during the current coronavirus disease 2019 (COVID-19) pandemic, given the rapid pace and unprecedented volume of research being conducted in such a short time, and the large number of reports submitted to journals.
June 25, 2020
To our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19. Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients. This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy.
Covid-19 and the Need for Health Care Reform
The Covid-19 pandemic has brought into sharp focus the need for health care reforms that promote universal access to affordable care. Although all aspects of U.S. health care will face incredible challenges in the coming months, the patchwork way we govern and pay for health care is unraveling in this time of crisis, leaving millions of people vulnerable and requiring swift, coordinated political action to ensure access to affordable care.
June 24, 2020
A coordinated response with contact tracing and testing of all contacts, including those who are asymptomatic, is important in controlling future COVID-19 outbreaks that might occur as schools and universities consider reopening.
Mortality, Admissions, and Patient Census at SNFs in 3 US Cities During the COVID-19 Pandemic
Mortality from coronavirus disease 2019 (COVID-19) is disproportionately concentrated in skilled nursing facilities (SNFs). As of June 18, 2020, 50 185 residents died of COVID-19 in the 41 states reporting deaths at SNFs, accounting for 45% of their total COVID-19 deaths statewide.
A Proposed Lottery System to Allocate Scarce COVID-19 Medications
These problems are not specific to remdesivir or to the current pandemic: governments and health systems will predictably encounter situations during pandemics in which novel therapeutics are in short supply and knowledge about their harms and benefits is limited.
Missed Opportunities on Emergency Remdesivir Use
In the case of remdesivir, the decision to grant an EUA followed the release of a summary interim finding of shorter time to recovery among patients treated with the drug in a National Institute of Allergy and Infectious Diseases (NIAID)–funded phase 3 placebo-controlled clinical trial.
June 23, 2020
Despite various levels of preventive measures, in 2020 many countries have suffered severely from the coronavirus 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. We show that population heterogeneity can significantly impact disease-induced immunity as the proportion infected in groups with the highest contact rates is greater than in groups with low contact rates.
It was the first week of my oncology fellowship, and Dr. E., a senior fellow, was handing his patients over to me, as he was shifting from clinical work to research. He had emailed signout the night before, but this in-person meeting communicated all the nuance that a spreadsheet lacked — how Mr. R., for example, liked his chemotherapy scheduled around calving season. Having been a medicine resident just a week earlier, I knew minimal oncology. But this meeting was not about the science. It was about the stories.
June 22, 2020
Detection of SARS-CoV-2 infections to date has relied heavily on RT-PCR testing. However, limited test availability, high false-negative rates, and the existence of asymptomatic or sub-clinical infections have resulted in an under-counting of the true prevalence of SARS-CoV-2.
In the 10 weeks following declaration of the COVID-19 national emergency, ED visits declined 23% for heart attack, 20% for stroke, and 10% for hyperglycemic crisis.
June 18, 2020
Challenges of “Return to Work” in an Ongoing Pandemic
As economic and political pressure has built to relax “shelter in place” public health orders for control of coronavirus disease 2019 (Covid-19), industry, professional service firms, retail and service establishments, and educational institutions seek to establish norms that protect workers, customers, clients, students, and visitors. A public health order represents a minimum disease-prevention standard, adherence to which is not elective, but may not satisfy all legal requirements with respect to the personal safety of workers and others.
Association between high serum total cortisol concentrations and mortality from COVID-19
Physiological stress from critical illness and elective surgery increases serum cortisol concentrations and bioavailability by activation of the hypothalamic–pituitary–adrenal axis, decreased metabolism of cortisol, and a reduction in the amount of binding proteins (eg, cortisol-binding globulin).
Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections
These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.
June 17, 2020
Genomewide Association Study of Severe Covid-19 with Respiratory Failure
We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.)
June 15, 2020
Coronavirus Disease 2019 Case Surveillance — United States, January 22–May 30, 2020
As of May 30, 2020, among COVID-19 cases, the most common underlying health conditions were cardiovascular disease (32%), diabetes (30%), and chronic lung disease (18%). Hospitalizations were six times higher and deaths 12 times higher among those with reported underlying conditions compared with those with none reported.
Hospital-Wide SARS-CoV-2 Antibody Screening in 3056 Staff in a Tertiary Center in Belgium
Belgium has a high burden of coronavirus disease 2019 (COVID-19), especially the region surrounding the Hospital East-Limburg, a tertiary care center.1 Infection prevention measures were instituted in the hospital beginning March 4, 2020, including testing and contact tracing of all symptomatic patients and staff, changes in hospital operations, and provision of personal protective equipment (PPE). The first case was detected March 13 (Figure 1). We investigated the prevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among hospital staff.
Monoclonal Antibodies for Prevention and Treatment of COVID-19
The coronavirus disease 2019 (COVID-19) pandemic has created a worldwide crisis and inspired an urgent search for prevention and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Attention has focused on the development of vaccines, new antiviral agents, and convalescent plasma infusions. Monoclonal antibodies have received less attention even though neutralizing antibodies are a key component of protective immunity for most viral diseases. Neutralizing monoclonal antibodies to SARS-CoV-2 have the potential for both therapeutic and prophylactic applications, and can help to guide vaccine design and development.
June 13, 2020
The third replenishment meeting for Gavi, the Vaccine Alliance, on June 4, which raised a record US$8·8 billion for the next 5 years, was overshadowed by the COVID-19 global pandemic and the burning question of how to ensure equita-ble access to any vaccines that become available.
June 11, 2020
The Dual Epidemics of COVID-19 and Influenza
The health system, and wider society, must prepare for the likelihood of co-epidemics of COVID-19 and influenza. What are the most effective strategies for increasing influenza vaccine coverage across the population and particularly in schools, businesses, and hospitals? Should states or businesses require vaccinations? Influenza vaccination, moreover, could offer valuable lessons for ensuring vaccine acceptance and uptake when COVID-19 vaccines become available.
June 10, 2020
The Importance of Proper Death Certification During the COVID-19 Pandemic
Death certificate data are used to monitor local, regional, and national mortality trends to improve public health and public safety. Accurate death certification related to coronavirus disease 2019 (COVID-19) is vital to understand the extent and progression of the pandemic.
Sustaining Rural Hospitals After COVID-19
The coronavirus disease 2019 (COVID-19) pandemic is a financial stress test for US hospitals.1,2 Revenues have declined from the suspension of elective procedures and nonessential services, and many hospitals have experienced a surge of critically ill patients.
June 8, 2020
Severe coronavirus disease 2019 (COVID-19) has been reported rarely in children.1,2 International data suggest the development of a proinflammatory syndrome with features of Kawasaki disease (KD) or toxic shock syndrome (TSS) in children, possibly related to COVID-19.
Data from China found severe complications in 8% of pregnant women with coronavirus disease 2019 (COVID-19).1 However, the high rate of cesarean deliveries (>90%) in Chinese reports is concerning,2 and whether mode of delivery is associated with maternal complications or neonatal transmission is unknown.3 We assessed births to women with COVID-19 by mode of delivery.
These findings help characterize the clinical features of hospitalized, seriously ill children with PIMS-TS and provide insights into this apparently novel syndrome.
June 5, 2020
False Negative Tests for SARS-CoV-2 Infection — Challenges and Implications
There is broad consensus that widespread SARS-CoV-2 testing is essential to safely reopening the United States. A big concern has been test availability, but test accuracy may prove a larger long-term problem.
Waiting for Certainty on Covid-19 Antibody Tests — At What Cost?
Governments around the world and throughout the United States are beginning to “reopen their economies” in stages. Some have been considering the use of serologic antibody testing to screen for possible immunity and to identify people who could return to the workplace with less severe mitigation measures or be assigned to higher-exposure tasks. Although availability of antibody tests is lagging and successful mitigation has kept seroprevalence too low to rely fully on positive test results, at some point in the near future antibody testing will become a viable option. This idea is not without its critics.
June 4, 2020
Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article, “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.”
June 3, 2020
The ongoing outbreak of Kawasaki-like multisystem inflammatory syndrome among children and adolescents in the Paris area might be related to SARS-CoV-2. In this study an unusually high proportion of the affected children and adolescents had gastrointestinal symptoms, Kawasaki disease shock syndrome, and were of African ancestry.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and is spread person-to-person through close contact. We aimed to investigate the effects of physical distance, face masks, and eye protection on virus transmission in health-care and non-health-care (eg, community) settings.
June 1, 2020
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and is spread person-to-person through close contact. We aimed to investigate the effects of physical distance, face masks, and eye protection on virus transmission in health-care and non-health-care (eg, community) settings.
Airborne Spread of SARS-CoV-2 and a Potential Role for Air Disinfection
Although clear evidence of person-to-person airborne transmission of SARS-CoV-2 has not been published, an airborne component of transmission is likely based on other respiratory viruses such as SARS, Middle East respiratory syndrome, and influenza. While air sampling for SARS-CoV-2, in a clinical setting, has demonstrated detectable viral RNA, the extent of transmission resulting from airborne particles relative to large respiratory droplets, directly and on surfaces, is not yet known.
The Urgency and Challenge of Opening K-12 Schools in the Fall of 2020
Reopening schools this fall is an urgent national priority. To achieve this goal as safely as possible and reduce the chances that schools are required to close again, policy makers at every level should consider embracing a framework with these 6 components.
May 29, 2020
A COVID-19 vaccine has passed its first human trial. But is it the frontrunner?
A promising coronavirus vaccine candidate cleared a key hurdle this week, when Moderna Therapeutics entered phase two of clinical trials. The move signals that the company’s mRNA vaccine has passed its initial safety checks and has met an important milestone in bringing this drug closer to the public and commercial markets.
May 28, 2020
Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study
Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments.
COVID-19: in the footsteps of Ernest Shackleton
We describe what we believe is the first instance of complete COVID-19 testing of all passengers and crew on an isolated cruise ship during the current COVID-19 pandemic. Of the 217 passengers and crew on board, 128 tested positive for COVID-19 on reverse transcription–PCR (59%). Of the COVID-19-positive patients, 19% (24) were symptomatic; 6.2% (8) required medical evacuation; 3.1% (4) were intubated and ventilated; and the mortality was 0.8% (1). The majority of COVID-19-positive patients were asymptomatic (81%, 104 patients). We conclude that the prevalence of COVID-19 on affected cruise ships is likely to be significantly underestimated, and strategies are needed to assess and monitor all passengers to prevent community transmission after disembarkation.
May 27, 2020
Reducing transmission of SARS-CoV-2
Respiratory infections occur through the transmission of virus-containing droplets (>5 to 10 μm) and aerosols (≤5 μm) exhaled from infected individuals during breathing, speaking, coughing, and sneezing. Traditional respiratory disease control measures are designed to reduce transmission by droplets produced in the sneezes and coughs of infected individuals. However, a large proportion of the spread of coronavirus disease 2019 (COVID-19) appears to be occurring through airborne transmission of aerosols produced by asymptomatic individuals during breathing and speaking.
How can airborne transmission of COVID-19 indoors be minimised?
Appropriate building engineering controls include sufficient and effective ventilation, possibly enhanced by particle filtration and air disinfection, avoiding air recirculation and avoiding overcrowding. Often, such measures can be easily implemented and without much cost, but if only they are recognised as significant in contributing to infection control goals. We believe that the use of engineering controls in public buildings, including hospitals, shops, offices, schools, kindergartens, libraries, restaurants, cruise ships, elevators, conference rooms or public transport, in parallel with effective application of other controls (including isolation and quarantine, social distancing and hand hygiene), would be an additional important measure globally to reduce the likelihood of transmission and thereby protect healthcare workers, patients and the general public.
Important findings include the presence of thrombosis and microangiopathy in the small vessels and capillaries of the lungs, with associated haemorrhage, that significantly contributed to death. Features of diffuse alveolar damage, including hyaline membranes, were present, even in patients who had not been ventilated. Cardiac findings included individual cell necrosis without lymphocytic myocarditis. There was no evidence of secondary pulmonary infection by microorganisms.
Coronavirus disease 2019 (COVID-19) emerged in Wuhan, China, in December 2019 and has spread globally with sustained human-to-human transmission outside China.1,2 To control the spread of COVID-19 and isolate patients as early as possible, the Chinese government requested that close contacts of individuals with COVID-19 must be screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. During the screening process, we found some patients whose test results were positive for SARS-CoV-2 but who had no symptoms or signs throughout the course of the disease.
May 26, 2020
One Key Factor in whether COVID-19 Will Wane This Summer
So far, scientists have identified at least nine distinct viruses that can cause respiratory tract infection and that express seasonality in their outbreak pattern in temperate regions. Of these, three viruses—influenza, human coronavirus and human respiratory syncytial virus (RSV) – clearly peak during winter months.
Prevalence of SARS-CoV-2 Among Patients Admitted for Childbirth in Southern Connecticut
Developing an approach to care for pregnancy and childbirth during the coronavirus disease 2019 (COVID-19) crisis is a priority to (1) provide safe care to pregnant women and newborns; and (2) protect health care workers from infection. A study conducted in New York City reported a 13.5% prevalence of asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in women presenting for childbirth.1 On March 30, 2020, an initially asymptomatic woman admitted to the Yale New Haven Health system developed cough and fever soon after childbirth; testing confirmed SARS-CoV-2 infection. This event prompted the development of a SARS-CoV-2 screening and testing program of patients presenting for childbirth; we report the prevalence detected in the first weeks of the program.
Adverse Consequences of Rushing a SARS-CoV-2 Vaccine
As the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic persists across the US and the world, the spotlight on vaccine science has never been more intense. Researchers across the globe are working rapidly to produce a potential vaccine, and 7 candidates are already in clinical trials. Operation Warp Speed, the vaccine development project announced by President Trump, has advocated for a vaccine to be made available in the US by the beginning of 2021. But for scientists and physicians, the term “warp speed” should trigger concern. Good science requires rigor, discipline, and deliberate caution. Any medical therapy approved for public use in the absence of extensive safeguards has the potential to cause harm, not only for COVID-19 prevention efforts and vaccine recipients, but also for public trust in vaccination efforts worldwide.
May 25, 2020
COVID-19-associated hyperviscosity: a link between inflammation and thrombophilia?
Reports of thrombotic complications in patients with COVID-19 are increasingly prominent, and these reports include patients receiving therapeutic anticoagulation.At our institution, multiple occurrences of anticoagulation failure prompted us to search for alternative aetiologies contributing to refractory hypercoagulability.
May 22, 2020
Remdesivir for the Treatment of Covid-19 — Preliminary Report
Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious.
Hydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit. Although generally safe when used for approved indications such as autoimmune disease or malaria, the safety and benefit of these treatment regimens are poorly evaluated in COVID-19.
Cloth Masks May Prevent Transmission of COVID-19: An Evidence-Based, Risk-Based Approach
Physical distancing, hand hygiene, and disinfection of surfaces are the cornerstones of infection control during the coronavirus disease 2019 (COVID-19) pandemic. At the same time, governments, international agencies, policymakers, and public health officials have been debating the validity of recommending use of nonmedical masks by the general public to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We believe that these decisions should be informed by evidence.
A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain.
After identification of two cases of COVID-19 in an SNF in Los Angeles, universal, serial reverse transcription–polymerase chain reaction (RT-PCR) testing of residents and staff members aided in rapid identification of additional cases and isolation and cohorting of these residents and interruption of transmission in the facility.
On March 13, 2020, the United States declared a national state of emergency to control the pandemic spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) . Public health response measures to mitigate the pandemic have centered on social distancing and quarantine policies, including shelter-in-place and stay-at-home orders.
High COVID-19 Attack Rate Among Attendees at Events at a Church — Arkansas, March 2020
Faith-based organizations should work with local health officials to determine how to implement the U.S. Government guidelines for modifying activities during the COVID-19 pandemic to prevent transmission of the virus to their members and their communities.
May 21, 2020
Enlisting Monoclonal Antibodies in the Fight Against COVID-19
We now know that the immune system of nearly everyone who recovers from COVID-19 produces antibodies against SARS-CoV-2, the novel coronavirus that causes this easily transmitted respiratory disease [1]. The presence of such antibodies has spurred hope that people exposed to SARS-CoV-2 may be protected, at least for a time, from getting COVID-19 again. But, in this post, I want to examine another potential use of antibodies: their promise for being developed as therapeutics for people who are sick with COVID-19.
Postmortem Examination of Patients With COVID-19
Approximately 15% of individuals affected by coronavirus disease 2019 (COVID-19) develop severe disease, and 5% to 6% are critically ill (respiratory failure and/or multiple organ dysfunction or failure).1,2 Severely ill and critically ill patients have a high mortality rate, especially with older age and coexisting medical conditions. Because there are still insufficient data on cause of death, we describe postmortem examinations in a case series of patients with COVID-19.
Coronavirus Antibody Tests—What They Tell Us
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Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19
Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19.
Covid-19, Angiogenesis, and ARDS Endotypes
The SARS-CoV-2 pandemic has inspired new interest in understanding the fundamental pathology of acute respiratory distress syndrome (ARDS), which has been associated with severe coronavirus disease 2019 (Covid-19). ARDS has long been recognized to be remarkably heterogeneous, with not only a wide range of causes but also a broad spectrum of severity, abnormalities on imaging, and gas-exchange impairment. The form of ARDS that is associated with Covid-19 is no different.
May 20, 2020
Nasal Gene Expression of Angiotensin-Converting Enzyme 2 in Children and Adults
Children account for less than 2% of identified cases of coronavirus disease 2019 (COVID-19).1,2 It is hypothesized that the lower risk among children is due to differential expression of angiotensin-converting enzyme 2 (ACE2),3 the receptor that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses for host entry.4 We investigated ACE2 gene expression in the nasal epithelium of children and adults.
May 19, 2020
Personal Protective Equipment and Covid-19
Given the threat of coronavirus disease 2019, or Covid-19, it is important to emphasize the use of proper precautions for infection control in health care settings. Severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, is the virus that causes Covid-19.
The Covid-19 Pandemic and the Incidence of Acute Myocardial Infarction
During the Covid-19 pandemic, reports have suggested a decrease in the number of patients presenting to hospitals because of emergency conditions such as acute myocardial infarction.
Renin–Angiotensin–Aldosterone System Inhibitors in Covid-19
In their Special Report, Vaduganathan and colleagues (April 23 issue)1 describe the use of renin–angiotensin–aldosterone system (RAAS) inhibitors in patients with coronavirus disease 2019 (Covid-19).
May 18, 2020
Silent COVID-19: what your skin can reveal
Clinical manifestations of coronavirus disease 2019 (COVID-19) are rare or absent in children and adolescents hence, early clinical detection is fundamental to prevent further spreading. We report three young patients presenting with chilblain-like lesions who were diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Inadequate knowledge about the extent of the coronavirus disease 2019 (COVID-19) epidemic challenges public health response and planning. Most reports of confirmed cases rely on polymerase chain reaction–based testing of symptomatic patients.1 These estimates of confirmed cases miss individuals who have recovered from infection, with mild or no symptoms, and individuals with symptoms who have not been tested due to limited availability of tests.
Planning for a COVID-19 Vaccination Program
The long-term solution to the coronavirus disease 2019 (COVID-19) pandemic, hopefully, will be a globally implemented, safe vaccination program that has broad clinical and socioeconomic benefits. Dozens of vaccines are in development, with 8 currently in phase 1 trials. Some scenarios predict the earliest, widespread availability of a COVID-19 vaccine to be in 2021.
Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)
It has been more than a century since the world has encountered a pandemic like coronavirus disease 2019 (COVID-19), and the rate of spread of COVID-19 around the globe and the associated morbidity and mortality have been staggering.
Implications for Telehealth in a Postpandemic Future
The coronavirus disease 2019 (COVID-19) pandemic has required health care systems to radically and rapidly rethink the delivery of care. One of the most remarkable ongoing changes has been the unprecedented accelerated expansion of telehealth. T
COVID-19 and the Need for a National Health Information Technology Infrastructure
The need for timely, accurate, and reliable data about the health of the US population has never been greater. Critical questions include the following: (1) how many individuals test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and how many are affected by the disease it causes—novel coronavirus disease 2019 (COVID-19) in a given geographic area; (2) what are the age and race of these individuals; (3) how many people sought care at a health care facility; (4) how many were hospitalized; (5) within individual hospitals, how many patients required intensive care, received ventilator support, or died; and (6) what was the length of stay in the hospital and in the intensive care unit for patients who survived and for those who died.
Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)
It has been more than a century since the world has encountered a pandemic like coronavirus disease 2019 (COVID-19), and the rate of spread of COVID-19 around the globe and the associated morbidity and mortality have been staggering.
May 17, 2020
This is the study with relatively large sample size that mainly focused on the duration of viral shedding and relevant factors in patients with COVID-19 outside of Wuhan, China. Potential risk factors were identified and should be taken into consideration for the strategy of quarantine of infected patients.
May 16, 2020
The COVID-19 pandemic continues to worsen in the USA with 1·3 million cases and an estimated death toll of 80 684 as of May 12. States that were initially the hardest hit, such as New York and New Jersey, have decelerated the rate of infections and deaths after the implementation of 2 months of lockdown. However, the emergence of new outbreaks in Minnesota, where the stay-at-home order is set to lift in mid-May, and Iowa, which did not enact any restrictions on movement or commerce, has prompted pointed new questions about the inconsistent and incoherent national response to the COVID-19 crisis.
May 15, 2020
The most common initial symptoms of coronavirus disease 2019 (Covid-19) are fever, cough, fatigue, anorexia, myalgias, and diarrhea.1 Severe illness usually begins approximately 1 week after the onset of symptoms. Dyspnea is the most common symptom of severe disease and is often accompanied by hypoxemia2,3 (Figure 1).
Pandemic Could Add Noise to Clinical Trial Data
Investigational ChAdOx1 nCoV-19 vaccine protects monkeys against COVID-19 pneumonia
A single dose of ChAdOx1 nCoV-19, an investigational vaccine against SARS-CoV-2, has protected six rhesus macaques from pneumonia caused by the virus, according to National Institutes of Health scientists and University of Oxford collaborators. SARS-CoV-2 is the virus that causes COVID-19.
May 14, 2020
The Centers for Disease Control and Prevention (CDC) is providing 1) background information on several cases of a recently reported multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19); and 2) a case definition for this syndrome. CDC recommends healthcare providers report any patient who meets the case definition to local, state, and territorial health departments to enhance knowledge of risk factors, pathogenesis, clinical course, and treatment of this syndrome.
Asymptomatic Seroconversion of Immunoglobulins to SARS-CoV-2 in a Pediatric Dialysis Unit
Dialysis units are at especially high risk of infectious disease transmission, and concern exists about spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Dialysis units in Wuhan, China, have reported high coronavirus disease 2019 (COVID-19) prevalence, due in part to unique exposure challenges that limit social distancing efforts, including open bay formats and rotating/multiple nursing assignments.1,2 This study describes SARS-CoV-2 seroconversion in patients and health care workers in a pediatric dialysis unit.
Emergency Use Authorization of Remdesivir
The Need for a Transparent Distribution Process
On February 4, 2020, the Secretary of the US Department of Health and Human Services (DHHS) determined that there was a public health emergency due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). On March 27, 2020, the DHHS secretary declared that circumstances existed to justify the authorization of emergency use of drugs and biologics during the coronavirus disease 2019 (COVID-19) outbreak, pursuant to section 564 of the Federal Food, Drug, and Cosmetic Act
May 13, 2020
Multiorgan and Renal Tropism of SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) preferentially infects cells in the respiratory tract,1,2 but its direct affinity for organs other than the lungs remains poorly defined. Here, we present data from an autopsy series of 27 patients (see the clinical data in Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org) that show that SARS-CoV-2 can be detected in multiple organs, including the lungs, pharynx, heart, liver, brain, and kidneys.
Treatment of COVID-19 Patients with Convalescent Plasma in Houston, Texas
Background: COVID-19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally, and no proven treatments are available. Convalescent plasma therapy has been used with varying degrees of success to treat severe microbial infections for more than 100 years.
Speech droplets generated by asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are increasingly considered to be a likely mode of disease transmission. Highly sensitive laser light scattering observations have revealed that loud speech can emit thousands of oral fluid droplets per second. In a closed, stagnant air environment, they disappear from the window of view with time constants in the range of 8 to 14 min, which corresponds to droplet nuclei of ca. 4 μm diameter, or 12- to 21-μm droplets prior to dehydration. These observations confirm that there is a substantial probability that normal speaking causes airborne virus transmission in confined environments.
Kawasaki-like disease: emerging complication during the COVID-19 pandemic
Children have to date borne a minimal medical burden in the global COVID-19 pandemic. Epidemiological data from many countries show that children are a small minority of those who test positive. Children younger than 18 years have made up only 1·7% of national cases in the USA, 1% of cases in the Netherlands, and 2·0% of a large observational cohort in the UK. Whether these proportions reflect lower susceptibility among children versus adults, or similar infection rates, but much higher proportions with asymptomatic disease, is unclear.
May 12, 2020
Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody
SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 20201,2. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus.
The potential for superspreader events underscores the importance of physical distancing, including avoiding gathering in large groups, to control spread of COVID-19. Enhancing community awareness can encourage symptomatic persons and contacts of ill persons to isolate or self-quarantine to prevent ongoing transmission.
May 11, 2020
Real-time tracking of self-reported symptoms to predict potential COVID-19
A total of 2,618,862 participants reported their potential symptoms of COVID-19 on a smartphone-based app. Among the 18,401 who had undergone a SARS-CoV-2 test, the proportion of participants who reported loss of smell and taste was higher in those with a positive test result (4,668 of 7,178 individuals; 65.03%) than in those with a negative test result (2,436 of 11,223 participants; 21.71%) (odds ratio = 6.74; 95% confidence interval = 6.31–7.21). A model combining symptoms to predict probable infection was applied to the data from all app users who reported symptoms (805,753) and predicted that 140,312 (17.42%) participants are likely to have COVID-19.
Virus impact on Louisiana state finances pegged at $1B
Louisiana's forecasting panel Monday slashed the state's income projections by $1 billion because of the coronavirus outbreak, blowing a hole in next year's budget as the virus's economic fallout threatens deep cuts across state services.
Among patients hospitalized with COVID-19, treatment with hydroxychloroquine, azithromycin, or both was not associated with significantly lower in-hospital mortality.
Monitoring travelers was labor-intensive and limited by incomplete information, volume of travelers, and potential for asymptomatic transmission. Health departments need to weigh the resources needed for monitoring against those needed for implementing mitigation activities during the COVID-19 pandemic.
SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), was first identified in December 2019 in Wuhan, China, and has since spread worldwide. On March 11, 2020, the World Health Organization declared COVID-19 a pandemic (1). That same day, the first confirmed COVID-19–associated fatality occurred in New York City (NYC). To identify confirmed COVID-19–associated deaths, defined as those occurring in persons with laboratory-confirmed SARS-CoV-2 infection, on March 13, 2020, the New York City Department of Health and Mental Hygiene (DOHMH) initiated a daily match between all deaths reported to the DOHMH electronic vital registry system (eVital) (2) and laboratory-confirmed cases of COVID-19.
COVID-19 and Postinfection Immunity Limited Evidence, Many Remaining Questions
In summary, existing limited data on antibody responses to SARS-CoV-2 and related coronaviruses, as well as one small animal model study, suggest that recovery from COVID-19 might confer immunity against reinfection, at least temporarily. However, the immune response to COVID-19 is not yet fully understood and definitive data on postinfection immunity are lacking. Amidst the uncertainty of this public health crisis, thoughtful and rigorous science will be essential to inform public health policy, planning, and practice.
COVID-19 and Racial/Ethnic Disparities
The novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has led to a global pandemic manifested as coronavirus disease 2019 (COVID-19), with its most severe presentation being acute respiratory distress syndrome leading to severe complications and death.
COVID-19 and Health Equity—A New Kind of “Herd Immunity”
Three articles recently published in JAMA provide insight into the large racial/ethnic differences associated with coronavirus disease 2019 (COVID-19) and highlight the need for, and potential opportunity to, redouble efforts in the US to develop strategies that would enable society to slow and ultimately eliminate the spread of inequities in health.
May 10, 2020
In two independent cohorts of patients with heart failure, plasma concentrations of ACE2 were higher in men than in women, but use of neither an ACE inhibitor nor an ARB was associated with higher plasma ACE2 concentrations. These data might explain the higher incidence and fatality rate of COVID-19 in men, but do not support previous reports suggesting that ACE inhibitors or ARBs increase the vulnerability for COVID-19 through increased plasma ACE2 concentrations.
May 8, 2020
Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir–ritonavir, and ribavirin for treating patients with COVID-19.Methods
The first reported case of coronavirus disease 2019 (COVID-19) in the US occurred on January 20, 2020, in Snohomish County, Washington.1 The University of Washington (UW) Virology Division was among the first US laboratories to test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and since March 1, 2020, has tested samples from more than 73 000 patients. More than 90% of the samples are from the UW health system and outpatient clinics in Washington State.
The positivity rates for SARS-CoV-2 in outpatient settings in Washington State and in emergency departments (EDs) in Seattle were analyzed to identify temporal trends that may reflect the local dynamics of the pandemic and the effect of mitigation strategies such as physical distancing.
When Should Clinicians Act on Non–Statistically Significant Results from Clinical Trials?
Understanding whether the results of a randomized clinical trial (RCT) are clinically actionable is challenging. Reporting standards adopted by JAMA and other leading journals lead to relative uniformity of presentation of RCT findings that help simplify critical appraisal.
Association between Angiotensin Blockade and Incidence of Influenza in the United Kingdom
Some researchers have hypothesized that drugs that interfere with the renin–angiotensin–aldosterone system (RAAS), including angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs), may increase susceptibility to coronaviruses. This hypothesis is based on the observation that coronaviruses engage ACE2 for cell entry1 and that altered expression of ACE2 is influenced by the use of ACE inhibitors and ARBs, an action that has been shown in animal models.2 Influenza A (H7N9, H1N1, and H5N1) has been shown to use the ACE2 receptor to mediate lung damage, similar to that seen in severe acute respiratory syndrome (SARS).3 Understanding the shared mechanism between SARS and influenza may help to address the question as to how ACE inhibitors and ARBs may modulate the manifestations of certain viral respiratory infections.
Collateral Effect of Covid-19 on Stroke Evaluation in the United States
The effect of the Covid-19 pandemic on medical care for conditions other than Covid-19 has been difficult to quantify.1 Any decrease in care for patients with acute conditions such as ischemic stroke may be consequential because timely treatment may decrease the incidence of disability.
Suppressing the Epidemic in New South Wales
Facing the coronavirus pandemic, Australia has achieved national consensus on policies that were unprecedented for the past century. New South Wales (which has 8 million residents) and other jurisdictions appear to have successfully suppressed Covid-19 transmission after a rapid escalation of cases in March 2020.
May 7, 2020
Clinical Characteristics and Results of Semen Tests Among Men with Coronavirus Disease 2019
In December 2019, an outbreak of pneumonia associated with coronavirus disease 2019 (COVID-19) occurred in Wuhan, China, and rapidly spread to other parts of China and overseas.1 It has been confirmed that COVID-19 has the characteristic of human-to-human transmission, mainly through respiratory droplets and contact. Other routes require further verification. The virus responsible for COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected in stool, gastrointestinal tract, saliva, and urine samples.2 However, little is known about SARS-CoV-2 in semen.
Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19
In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed.
The Urgency of Care during the Covid-19 Pandemic — Learning as We Go
Chloroquine and hydroxychloroquine, alone or in combination with azithromycin, have been highly touted as potential therapies for Covid-19. The claims of efficacy are based largely on anecdotes and case series that have been described as being so persuasive that it would be unethical to perform studies with placebo controls.1 On the basis of this “evidence,” these therapies have been recommended in many guidelines, including some national policies, and have been widely implemented.
May 6, 2020
Interpreting Diagnostic Tests for SARS-CoV-2
The pandemic of coronavirus disease 2019 (COVID-19) continues to affect much of the world. Knowledge of diagnostic tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still evolving, and a clear understanding of the nature of the tests and interpretation of their findings is important. This Viewpoint describes how to interpret 2 types of diagnostic tests commonly in use for SARS-CoV-2 infections—reverse transcriptase–polymerase chain reaction (RT-PCR) and IgM and IgG enzyme-linked immunosorbent assay (ELISA)—and how the results may vary over time
May 5, 2020
Adaptations and Lessons in the Province of Bergamo
Lombardy, and particularly the province of Bergamo, has been the area of Italy most affected by Covid-19. As of April 26, 2020, the province had 11,113 confirmed cases and 2932 deaths from Covid-19. Delays in recognizing SARS-CoV-2 in the few infected patients admitted to the small hospital in Alzano Lombardo — and delays in activating measures to protect other patients, hospital personnel, and visitors, as well as in implementing adequate containment measures in patients’ villages — allowed the virus to spread rapidly and into the city of Bergamo.
Lupus Anticoagulant and Abnormal Coagulation Tests in Patients with Covid-19
Patients with coronavirus disease 2019 (Covid-19) have a profound hypercoagulable state, and complicating venous thrombotic events are common.1-3 Abnormalities in coagulation screening measures, including a prolonged activated partial-thromboplastin time (aPTT), have been reported in patients with Covid-19.4 This finding could be seen as a reason to avoid the use of anticoagulation at both therapeutic and prophylactic doses.
A Trial of Lopinavir–Ritonavir in Covid-19
After a review of the findings of Cao et al. (published in the Journal online on March 18),1 many clinicians are abandoning the use of lopinavir–ritonavir for the treatment of Covid-19. We consider this action to be premature. It is crucial to realize that although this trial did not show that the time until clinical improvement was meaningfully better than standard care among patients with severe Covid-19 who received lopinavir–ritonavir, the trial was statistically underpowered to show this outcome.
May 4, 2020
Obesity could shift severe COVID-19 disease to younger ages
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 was first reported in China in late December, 2019, and has since evolved into a global pandemic. As of April 29, 2020, COVID-19 has been confirmed in more than 3 million individuals in 185 countries and regions, with an overall mortality rate of more than 6%.1Severe disease involves bilateral interstitial pneumonia requiring intensive care unit (ICU) ventilatory support and can evolve into adult respiratory distress syndrome with high mortality. The largest study of 1591 ICU patients from Italy reported a median age of 63 years, with only 203 patients (13%) younger than 51 years.Common comorbidities are hypertension, cardiovascular disease, type 2 diabetes, and, more rarely (42 [4%] of 1043), obstructive pulmonary disease. Similar data have been reported from China.
Profile of a killer: the complex biology powering the coronavirus pandemic
In 1912, German veterinarians puzzled over the case of a feverish cat with an enormously swollen belly. That is now thought to be the first reported example of the debilitating power of a coronavirus. Veterinarians didn’t know it at the time, but coronaviruses were also giving chickens bronchitis, and pigs an intestinal disease that killed almost every piglet under two weeks old.
A human monoclonal antibody blocking SARS-CoV-2 infection
The emergence of the novel human coronavirus SARS-CoV-2 in Wuhan, China has caused a worldwide epidemic of respiratory disease (COVID-19). Vaccines and targeted therapeutics for treatment of this disease are currently lacking. Here we report a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV) in cell culture.
Randomized Clinical Trials and COVID-19Managing Expectations
Despite the millions of cases and hundreds of thousands of deaths that have occurred in this devastating coronavirus disease 2019 (COVID-19) pandemic, no peer-reviewed studies of specific therapies proven to be effective in reducing mortality have been published and a vaccine is many months to years away. To date, more than 1000 studies addressing various aspects of COVID-19 are registered on ClinicalTrials.gov, including more than 600 interventional studies and randomized clinical trials (RCTs).
May 1, 2020
High transmissibility of COVID-19 before and immediately after symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to interrupt transmission, and that more generalized measures might be required, such as social distancing.
Production of the First Batch of Proposed COVID-19 Vaccines in the US Expected in July
Moderna, Inc. and Lonza Group AG announced a global agreement to manufacture one billion doses of Moderna's proposed vaccine every year, to be produced in the United States in July.
Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19
Coronavirus disease 2019 (Covid-19) may disproportionately affect people with cardiovascular disease. Concern has been aroused regarding a potential harmful effect of angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context.
Various factors contributed to accelerated spread during February–March 2020, including continued travel-associated importations, large gatherings, introductions into high-risk workplaces and densely populated areas, and cryptic transmission resulting from limited testing and asymptomatic and presymptomatic spread. Targeted and communitywide mitigation efforts were needed to slow transmission.
COVID-19 Among Workers in Meat and Poultry Processing Facilities ― 19 States, April 2020
COVID-19 cases among U.S. workers in 115 meat and poultry processing facilities were reported by 19 states. Among approximately 130,000 workers at these facilities, 4,913 cases and 20 deaths occurred. Factors potentially affecting risk for infection include difficulties with workplace physical distancing and hygiene and crowded living and transportation conditions.
Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19
Coronavirus disease 2019 (Covid-19) may disproportionately affect people with cardiovascular disease. Concern has been aroused regarding a potential harmful effect of angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context.
Renin–Angiotensin–Aldosterone System Blockers and the Risk of Covid-19
In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease. However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.
Inhibitors of the Renin–Angiotensin–Aldosterone System and Covid-19
From the viewpoint of human physiology, ACE2 plays an important regulatory role in the renin–angiotensin–aldosterone system (RAAS), metabolizing angiotensin II (a potent vasoconstrictor) to generate angiotensin-(1–7) (a vasodilator).2 Studies in animals have suggested that angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) may up-regulate ACE2 expression,3 thus increasing the availability of target molecules for SARS-CoV-2.
In the United States, approximately 1.4 million persons access emergency shelter or transitional housing each year (1). These settings can pose risks for communicable disease spread. In late March and early April 2020, public health teams responded to clusters (two or more cases in the preceding 2 weeks) of coronavirus disease 2019 (COVID-19) in residents and staff members from five homeless shelters in Boston, Massachusetts (one shelter); San Francisco, California (one); and Seattle, Washington (three).
COVID-19 Outbreak Among Three Affiliated Homeless Service Sites — King County, Washington, 2020
On March 30, 2020, Public Health – Seattle and King County (PHSKC) was notified of a confirmed case of coronavirus disease 2019 (COVID-19) in a resident of a homeless shelter and day center (shelter A). Residents from two other homeless shelters (B and C) used shelter A’s day center services.
April 30, 2020
A SARS-CoV-2 protein interaction map reveals targets for drug repurposing
The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection.
Clinical Characteristics of Coronavirus Disease 2019 in China
During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
Responding to Covid-19 — A Once-in-a-Century Pandemic?
In any crisis, leaders have two equally important responsibilities: solve the immediate problem and keep it from happening again. The Covid-19 pandemic is a case in point. We need to save lives now while also improving the way we respond to outbreaks in general. The first point is more pressing, but the second has crucial long-term consequences.
History in a Crisis — Lessons for Covid-19
Writing in the heady days of new antibiotics and immunizations, esteemed microbiologists Macfarlane Burnet and David White predicted in 1972 that “the most likely forecast about the future of infectious diseases is that it will be very dull.”1 They acknowledged that there was always a risk of “some wholly unexpected emergence of a new and dangerous infectious disease, but nothing of the sort has marked the last fifty years.” Epidemics, it seemed, were of interest only to historians.
Virtually Perfect? Telemedicine for Covid-19
Recognizing that patients prioritize convenient and inexpensive care, Duffy and Lee recently asked whether in-person visits should become the second, third, or even last option for meeting patient needs.1 Previous work has specifically described the potential for using telemedicine in disasters and public health emergencies.2 No telemedicine program can be created overnight, but U.S. health systems that have already implemented telemedical innovations can leverage them for the response to Covid-19.
Second-Trimester Miscarriage in a Pregnant Woman With SARS-CoV-2 Infection
No data exist regarding the effect on fetuses of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the first or second trimester of pregnancy, and data are limited regarding infections that occur during the third trimester. However, reports of newborns with fetal distress or requiring admission to the intensive care unit1,2 and a stillbirth after maternal coronavirus disease 2019 (COVID-19)3 in the third trimester suggest the possibility of COVID-19–induced placental pathology.
Mental Health in the Coronavirus Disease 2019 Emergency—The Italian Response
This article briefly reports the experience of mental health services and the lessons learned during the coronavirus disease 2019 (COVID-19) crisis. In particular, this report offers opportunities to build on experience gained in managing the COVID-19 emergency in the Departments of Mental Health and Addiction (DMHAs) in Lombardy, the wealthiest Italian region, which has approximately 10 million inhabitants.
Petechial Skin Rash Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection
The coronavirus disease 2019 (COVID-19) pandemic is filling the headlines these days. Although it is known that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be associated with skin manifestations, a limited number of images are available in the literature at this time. This observation reports dermatologic findings associated with a confirmed case of COVID-19.
April 29, 2020
Responding to the hidden pandemic for healthcare workers: stress
Healthcare workers are having to work under incredibly stressful conditions. Videoconferencing can be harnessed to provide mental-health support, but some report ‘tele-health’ fatigue. To protect public health, prepare for the mental-health surge among healthcare workers.
Covid-19 in Immune-Mediated Inflammatory Diseases — Case Series from New York
Data on Covid-19 in patients with immune-mediated inflammatory disease who have received anticytokine biologics, other immunomodulatory therapies, or both on a long-term basis are scarce. Trials to assess the efficacy of antirheumatic therapies such as hydroxychloroquine1 and anticytokine therapies such as interleukin-6 inhibitors2 to improve outcomes in patients with Covid-19 are ongoing.
In a cohort of 305 hospitalized adults with COVID-19 in Georgia (primarily metropolitan Atlanta), black patients were overrepresented, and their clinical outcomes were similar to those of nonblack patients. One in four hospitalized patients had no recognized risk factors for severe COVID-19.
April 28, 2020
The race for coronavirus vaccines: a graphical guide
More than 90 vaccines are being developed against SARS-CoV-2 by research teams in companies and universities across the world. Researchers are trialling different technologies, some of which haven’t been used in a licensed vaccine before.
Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young
We report five cases of large-vessel stroke in patients younger than 50 years of age who presented to our health system in New York City. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was diagnosed in all five patients.
Negative-Pressure Aerosol Cover for COVID-19 Tracheostomy
Because of the high virulence of the novel coronavirus responsible for causing COVID-19, many patients infected with the virus become critically ill, requiring prolonged intubation, and may ultimately require tracheostomy. Mucosal surfaces have been shown to be reservoirs for high concentrations of the virus, which can become aerosolized for up to 3 hours following manipulation.1,2 Surgeons performing tracheostomies are at high risk for exposure, and recently published guidelines recommend against elective, non–time-sensitive procedures.3 In the event that a tracheostomy is indicated in a patient with confirmed or suspected COVID-19, interventions that limit the spread of aerosols are critical to reducing exposure.4,5 Here we present the creation of a novel negative-pressure aerosol cover made out of readily available operating room materials as an additional barrier to limit the spread of aerosols during tracheostomy.
April 27, 2020
Rapidly transmitting COVID-19 has a short incubation period. The onset mainly occurs among young to middle-aged adults. Traffic restrictions played an important role in the decreased number of imported cases outside Hubei.
Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals
Our results indicate that room ventilation, open space, sanitization of protective apparel, and proper use and disinfection of toilet areas can effectively limit the concentration of SARS-CoV-2 RNA in aerosols. Future work should explore the infectivity of aerosolized virus.
Rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, prompted heightened surveillance in Shenzhen, China. The resulting data provide a rare opportunity to measure key metrics of disease course, transmission, and the impact of control measures.
Q&A: AAP president concerned about pandemic-related drop in vaccination rates
According to data from PCC, an independent firm that provides pediatric electronic health records software, pediatric vaccinations are down as a result of the COVID-19 pandemic.
Despite personal protective equipment, fluorescent markers were found on the uncovered skin, hair, and shoes of participants after simulations of emergency department management of patients experiencing respiratory distress. The findings suggest that the current recommendations for personal protective equipment may not fully prevent exposures in emergency department settings. Clothing that covers all skin may further diminish exposure risk.
COVID-19 and Risks Posed to Personnel During Endotracheal Intubation
Fundamental research is needed to better inform PPE recommendations. For example, it would be useful to know how long SARS-CoV-2 can remain infective on surfaces such as the skin, hair, and clothing, and the potential for contact transmission from those sites to guide recommendations for barrier protection. A better understanding of the duration of infectivity and level of risk posed by airborne SARS-CoV-2 would help to guide recommendations for respiratory protection. Much can be done to protect health care personnel performing endotracheal intubations from procedure-related transmission of COVID-19. Individuals who perform this life-saving procedure must be able to do it as safely as possible.
Prevalence of SARS-CoV-2 Infection in Residents of a Large Homeless Shelter in Boston
Universal SARS-CoV-2 PCR testing of an adult homeless shelter population in Boston shortly after the identification of a COVID-19 case cluster yielded a 36% positivity rate. The majority of individuals with newly identified infections had no symptoms and no fever at the time of diagnosis, suggesting that symptom screening in homeless shelters2 may not adequately capture the extent of disease transmission in this high-risk setting.
The Potential Effects of Coronavirus on National Health Expenditures
The first step in projecting how COVID-19 may affect the health share of the GDP is to estimate how COVID-19 will affect health care spending. This will depend on the future extent, timing, and composition of the pandemic, so it is highly uncertain.
April 25, 2020
Travel restrictions hampering COVID-19 response
The coronavirus disease 2019 (COVID-19) pandemic has sparked an unprecedented shutdown of borders and airlines, which is severely restricting the movement of essential medical personnel and supplies that are vital to stem the spread of the virus and save lives.
April 24, 2020
"Immunity passports" in the context of COVID-19
WHO has published guidance on adjusting public health and social measures for the next phase of the COVID-19 response.1 Some governments have suggested that the detection of antibodies to the SARS-CoV-2, the virus that causes COVID-19, could serve as the basis for an “immunity passport” or “risk-free certificate” that would enable individuals to travel or to return to work assuming that they are protected against re-infection. There is currently no evidence that people who have recovered from COVID-19 and have antibodies are protected from a second infection.
Clarification of Mortality Rate and Data in Abstract, Results, and Table 2
In the Original Investigation titled “Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area” published online April 22, 2020, in JAMA,1 clarification and correction of data were required.
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors’ clinical recommendations.
Coronavirus disease 2019 (COVID-19) has resulted in increased hospital and intensive care unit (ICU) use. In the United States, few reports have characterized patients treated outside of the ICU.1 Northern California was an early epicenter of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) community transmission in the United States. We report hospitalization and ICU admissions from Kaiser Permanente Northern California (KPNC), a regional integrated health care system serving 4.4 million members, constituting 30% of the area’s insured population.
Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility
Rapid and widespread transmission of SARS-CoV-2 was demonstrated in this skilled nursing facility. More than half of residents with positive test results were asymptomatic at the time of testing and most likely contributed to transmission. Infection-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission after SARS-CoV-2 introduction into this facility.
In this phase IIb randomized clinical trial of 81 patients with COVID-19, an unplanned interim analysis recommended by an independent data safety and monitoring board found that a higher dosage of chloroquine diphosphate for 10 days was associated with more toxic effects and lethality, particularly affecting QTc interval prolongation. The limited sample size did not allow the study to show any benefit overall regarding treatment efficacy.
A real-time dashboard of clinical trials for COVID-19
As trial findings are communicated, these data must be centralised and meta-analysed in real-time. Syntheses of these trials are urgently needed to assist clinicians, researchers, and policy makers to make evidence-informed decisions to minimise the morbidity and mortality due to COVID-19.
April 23, 2020
Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19
The renin–angiotensin–aldosterone system (RAAS) is an elegant cascade of vasoactive peptides that orchestrate key processes in human physiology. Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and SARS-CoV-2, which have been responsible for the SARS epidemic in 2002 to 2004 and for the more recent coronavirus disease 2019 (Covid-19) pandemic, respectively, interface with the RAAS through angiotensin-converting enzyme 2 (ACE2), an enzyme that physiologically counters RAAS activation but also functions as a receptor for both SARS viruses.
The coronavirus disease 2019 (COVID-19) outbreak was first identified in Wuhan, the capital of Hubei Province, China, in December 2019.1 The disease spread rapidly from Wuhan to other cities. To contain this epidemic, Wuhan was locked down on January 23, 2020. Wenzhou, which has a population of 9.3 million and is located in southeastern China approximately 600 miles from Wuhan, is the most affected Chinese city outside of Hubei.
South Korea extensively utilized the country’s advanced information technology (IT) system for tracing individuals suspected to be infected or who had been in contact with an infected person. Such measures helped flatten the curve of newly confirmed cases and deaths around mid-March.1,2(pp4-5) As of April 21, 2020, there had been 10 683 confirmed cases of COVID-19 in South Korea, with a total of 2233 patients who are in isolation because of hospitalization or quarantine, and a total of 237 deaths.3 However, important concerns have been raised over privacy involving the tracing strategy.
April 22, 2020
Saliva is more sensitive for SARS-CoV-2 detection in COVID-19 patients than nasopharyngeal swabs
When we compared SARS-CoV-2 detection from patient-matched nasopharyngeal and saliva samples, we found that saliva yielded greater detection sensitivity and consistency throughout the course of infection. Furthermore, we report less variability in self-sample collection of saliva. Taken together, our findings demonstrate that saliva is a viable and more sensitive alternative to nasopharyngeal swabs and could enable at-home self-administered sample collection for accurate large-scale SARS-CoV-2 testing.
Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection
Since December 2019, a pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally.1 A spectrum of disease severity has been reported, with main symptoms that include fever, fatigue, dry cough, myalgia, and dyspnea.
In this systematic review of 18 studies with 1065 participants, most pediatric patients with SARS-CoV-2 infection presented with fever, dry cough, and fatigue or were asymptomatic; 1 infant presented with pneumonia, complicated by shock and kidney failure, and was successfully treated with intensive care. Most pediatric patients were hospitalized, and symptomatic children received mainly supportive care; no deaths were reported in the age range of 0 to 9 years.
Timely antiviral therapy may slow COVID-19 progression; more study needed
Researchers in China found that hospitalized patients with milder cases of COVID-19 were treated earlier with an assortment of antivirals compared with patients who experienced more severe disease, suggesting that the timing of antiviral therapy may significantly slow COVID-19 progression.
Timeline reset: CDC confirms weeks-earlier California deaths
Health officials say two people died with the coronavirus in California weeks before the first reported death from the disease.
In this case series that included 5700 patients hospitalized with COVID-19 in the New York City area, the most common comorbidities were hypertension, obesity, and diabetes. Among patients who were discharged or died (n = 2634), 14.2% were treated in the intensive care unit, 12.2% received invasive mechanical ventilation, 3.2% were treated with kidney replacement therapy, and 21% died.
April 21, 2020
Ribonucleic acid (RNA) viral load measured in respiratory, stool, serum, and urine samples. Cycle threshold values, a measure of nucleic acid concentration, were plotted onto the standard curve constructed on the basis of the standard product. Epidemiological, clinical, and laboratory characteristics and treatment and outcomes data were obtained through data collection forms from electronic medical records, and the relation between clinical data and disease severity was analysed.
Ribonucleic acid (RNA) viral load measured in respiratory, stool, serum, and urine samples. Cycle threshold values, a measure of nucleic acid concentration, were plotted onto the standard curve constructed on the basis of the standard product. Epidemiological, clinical, and laboratory characteristics and treatment and outcomes data were obtained through data collection forms from electronic medical records, and the relation between clinical data and disease severity was analysed.
April 20, 2020
Health Care Heroes of the COVID-19 Pandemic
The COVID-19 pandemic has accounted for tens of thousands of deaths and ultimately will affect millions more people who will survive. There will be time to mourn the victims and care for the survivors. But it is also time to recognize and thank some of the heroes who have emerged so far.
On January 19, 2020, the state of Washington reported the first U.S. laboratory-confirmed case of coronavirus disease 2019 (COVID-19) caused by infection with SARS-CoV-2 (1). As of April 19, a total of 720,630 COVID-19 cases and 37,202 associated deaths* had been reported to CDC from all 50 states, the District of Columbia, and four U.S. territories (2). CDC recommends, with precautions, the proper cleaning and disinfection of high-touch surfaces to help mitigate the transmission of SARS-CoV-2 (3).
April 19,2020
Profile of RT-PCR for SARS-CoV-2: a preliminary study from 56 COVID-19 patients
A novel coronavirus (COVID-19) pandemic threatens the world. Here, we first studied the dynamics profile of SARS-CoV-2 from 56 recovered COVID-19 patients. We found virus shedding was up to 6 weeks after onset of symptoms. Prolonged observation period is necessary for older patients.
April 18, 2020
Will antibody tests for the coronavirus really change everything?
British Prime Minister Boris Johnson called them a ‘game changer’. Antibody tests have captured the world’s attention for their potential to help life return to normal by revealing who has been exposed, and might now be immune, to the new coronavirus.
Will antibody tests for the coronavirus really change everything?
Dozens of biotech companies and research laboratories have rushed to produce the blood tests. And governments around the world have bought millions of kits, in the hope that they could guide decisions on when to relax social-distancing measures and get people back to work. Some have even suggested that the tests could be used as an ‘immunity passport’, giving the owner clearance to interact with others again.
Flooded by the torrent: the COVID-19 drug pipeline
The coronavirus disease 2019 (COVID-19) drug pipeline is not growing at quite the same speed as the pandemic. But its rate of expansion is nevertheless cause for pause. In the months since COVID-19 has spread, researchers have launched more than 180 clinical trials of everything from repurposed antivirals and immunomodulators to unproven cell therapies and vitamin C. A further 150 trials are preparing to recruit patients.
COVID-19 exacerbating inequalities in the US
COVID-19 does not affect everyone equally. In the US, it is exposing inequities in the health system. Aaron van Dorn, Rebecca E Cooney, and Miriam L Sabin report from New York.
April 17, 2020
We found that ocular fluids from SARS-CoV-2-infected patients may contain infectious virus, and hence may be a potential source of infection. These findings highlight the importance of control measures, such as avoiding touching the nose, mouth, and eyes and frequent hand washing. A related implication is the importance of appropriate use of personal protective equipment for ophthalmologists during clinical examination, because ocular mucosa may be not only a site of virus entry but also a source of contagion. Furthermore, we observed that ocular involvement of SARS-CoV-2 may occur early in the COVID-19 course, suggesting that measures to prevent transmission via this route must be implemented as early as possible.
Masks and Coronavirus Disease 2019 (COVID-19)
Recent studies suggest that coronavirus disease 2019 (COVID-19) may be transmitted by infected persons even in the absence of symptoms of disease. While social distancing and good hand hygiene are the most important methods to prevent virus transmission, new guidelines state that healthy individuals can consider wearing masks in public settings, particularly when physical distancing is difficult (like in grocery stores or pharmacies). Primary benefits of wearing a mask include limiting the spread of the virus from someone who knows or does not know they have an infection to others.
In this cohort, screening only for fever, cough, shortness of breath, or sore throat might have missed 17% of symptomatic HCP at the time of illness onset; expanding criteria for symptoms screening to include myalgias and chills may still have missed 10%. The data indicate that HCP worked for several days while symptomatic, when, according to a growing body of evidence, they may transmit SARS-CoV-2 to vulnerable patients and other HCP.1 Interventions to prevent transmission from HCP include expanding symptoms-based screening criteria,2 furloughing symptomatic HCP,2 facilitating testing of symptomatic HCP,4 and creating sick leave policies that are nonpunitive, flexible, and consistent with public health guidance.5
From Mitigation to Containment of the COVID-19 Pandemic
Putting the SARS-CoV-2 Genie Back in the Bottle
The COVID-19 pandemic will one day be in the rearview mirror. US history will inevitably recount an early phase of the crisis plagued with denial, flawed testing, a patchwork response, and inadequate supplies that resulted in thousands of excess infections and deaths. Therefore, before the US “reopens,” the country must ensure that this chapter will end with a course-corrected public health strategy that promises widespread testing, resources for those affected, and a profound appreciation for an impressive, inspired, and tireless health care workforce that helped the US deal with this pandemic.
COVID-19—Looking Beyond Tomorrow for Health Care and Society
While acknowledging that there will be uncertainty in addressing the topics in the “COVID-19: Beyond Tomorrow” series, the insights from these Viewpoints should serve to help inform physicians, other health care professionals, administrators, and policy makers about what the future may hold with COVID-19 for health care and society. Perhaps these Viewpoints could also serve to provide suggestions to galvanize efforts about what will need to be done beyond tomorrow.
April 16, 2020
This platform is disease indication and disease mechanism‐agnostic, and potentially applicable to the systematic N‐of‐1 and population‐wide design of highly efficacious and tolerable clinical regimens. This work also discusses key factors ranging from healthcare economics to global health policy that may serve to drive the broader deployment of this platform to address COVID‐19 and future pandemics.
April 15, 2020
COVID-19 and African Americans
Public health is complicated and social reengineering is complex, but change of this magnitude does not happen without a new resolve. The US has needed a trigger to fully address health care disparities; COVID-19 may be that bellwether event. Certainly, within the broad and powerful economic and legislative engines of the US, there is room to definitively address a scourge even worse than COVID-19: health care disparities. It only takes will. It is time to end the refrain.
Rates of Co-infection Between SARS-CoV-2 and Other Respiratory Pathogens
These results suggest higher rates of co-infection between SARS-CoV-2 and other respiratory pathogens than previously reported, with no significant difference in rates of SARS-CoV-2 infection in patients with and without other pathogens. The presence of a non–SARS-CoV-2 pathogen may not provide reassurance that a patient does not also have SARS-CoV-2.
April 14, 2020
Stay 6 Feet Apart, We’re Told. But How Far Can Air Carry Coronavirus?
And scientists agree that six feet is a sensible and useful minimum distance, but, some say, farther away would be better.
FDA authorizes process it says could decontaminate 4 million masks daily
Amid widespread shortages of personal protective equipment and masks during the COVID-19 pandemic, the FDA has granted several emergency use authorizations, or EUAs, for the decontamination and reuse of N95 or N95-equivilent masks.
IDSA publishes ‘living guidelines’ on treatment of COVID-19
The Infectious Diseases Society of America published rapid guidelines on the treatment and management of patients with COVID-19 that mostly recommend recruiting patients into ongoing trials for investigational therapies.
CMS waiver on telehealth amid COVID-19 represents a ‘sea change’
CMS recently announced that video and chat apps that normally do not comply with HIPAA security and privacy regulations can be used to facilitate patient care during the COVID-19 public health emergency.
Weathering the cytokine storm in COVID-19: Telltale signs, therapeutic hope on the horizon
Good news about COVID-19 is at a premium these days. Encouraging reports about therapeutic options or vaccine development usually are either overly optimistic or entirely spurious. But scientific advancement is as relentless as the virus itself, and this is exemplified by a growing body of research into a potential association between cytokine storm syndrome and COVID-19.
Health care personnel (HCP) are at heightened risk of acquiring COVID-19 infection, but limited information exists about transmission in health care settings.
Spread of SARS-CoV-2 in the Icelandic Population
In a population-based study in Iceland, children under 10 years of age and females had a lower incidence of SARS-CoV-2 infection than adolescents or adults and males. The proportion of infected persons identified through population screening did not change substantially during the screening period, which was consistent with a beneficial effect of containment efforts.
Drug Evaluation during the Covid-19 Pandemic
The pandemic will inevitably leave considerable morbidity, mortality, and loss in its wake. Damage to the country’s medication-assessment process — and the public’s respect for it — should not be part of its legacy.
Not Dying Alone — Modern Compassionate Care in the Covid-19 Pandemic
There may be no way for families to hold patients’ hands or hug them while they’re dying, but with the care and compassion of frontline health care workers, maybe we can harness creative solutions to help them feel some connection, while still keeping everyone safe.
April 13, 2020
Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19)A Review
The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection.
Who Is Immune to the Coronavirus?
Among the many uncertainties that remain about Covid-19 is how the human immune system responds to infection and what that means for the spread of the disease. Immunity after any infection can range from lifelong and complete to nearly nonexistent. So far, however, only the first glimmers of data are available about immunity to SARS-CoV-2, the coronavirus that causes Covid-19.
Universal Screening for SARS-CoV-2 in Women Admitted for Delivery
The potential benefits of a universal testing approach include the ability to use Covid-19 status to determine hospital isolation practices and bed assignments, inform neonatal care, and guide the use of personal protective equipment. Access to such clinical data provides an important opportunity to protect mothers, babies, and health care teams during these challenging times.
Mental Health and the Covid-19 Pandemic
The Covid-19 pandemic has alarming implications for individual and collective health and emotional and social functioning. In addition to providing medical care, already stretched health care providers have an important role in monitoring psychosocial needs and delivering psychosocial support to their patients, health care providers, and the public — activities that should be integrated into general pandemic health care.
And I also know something about myself that I didn’t know even a few weeks ago: that as averse to risk as I am by nature, I would take on more if called to do so. The sentiments expressed by a character in The Plague, a novel by Albert Camus that I first read in high school, are no longer abstract to me: “I have no idea what’s awaiting me, or what will happen when this all ends,” says Dr. Rieux. “For the moment I know this: there are sick people and they need curing.”
For clinicians in areas that have not yet been hard hit, the pandemic wave will surely come. Persons under investigation for Covid-19 should be treated as if they are infected. These patients often have a progression of disease severity, with approximately 15% of admitted patients requiring upgrades in care. We hope that lessons from our center will help prepare other physicians and hospitals for what is likely to come so they can stay ahead of the wave.
April 6, 2020
In conclusion, both surgical and cotton masks seem to be ineffective in preventing the dissemination of SARS–CoV-2 from the coughs of patients with COVID-19 to the environment and external mask surface.
In this case series of critically ill patients with laboratory-confirmed COVID-19 admitted to ICUs in Lombardy, Italy, the majority were older men, a large proportion required mechanical ventilation and high levels of PEEP, and ICU mortality was 26%.
Coronavirus Disease 2019 in Children — United States, February 12–April 2, 2020
Pediatric COVID-19 patients might not have fever or cough. Social distancing and everyday preventive behaviors remain important for all age groups because patients with less serious illness and those without symptoms likely play an important role in disease transmission.
Sample Pooling as a Strategy to Detect Community Transmission of SARS-CoV-2
Strategies such as pooled screening may facilitate detection of early community transmission of SARS-CoV-2 and enable timely implementation of appropriate infection control measures to reduce spread.
April 3, 2020
Following identification of two COVID-19 cases in a Seattle independent and assisted living facility, stringent preventive measures were implemented. Testing of all residents and staff members found few cases of COVID-19. Three of four residents who had positive test results were asymptomatic.
Lessons from Covid-19 Hotspots
Eric J. Rubin, Lindsey R. Baden, and Stephen Morrissey
In this audio interview conducted April 1, the editors draw lessons from the early Covid-19 outbreak in Seattle and the growing crisis in New York City. Listen to the interview.
Barrier Enclosure during Endotracheal Intubation
Clinicians with inadequate access to standard personal protective equipment (PPE) have been compelled to improvise protective barrier enclosures for use during endotracheal intubation. We describe one such barrier that is easily fabricated and may help protect clinicians during this procedure.
Addressing the COVID-19 Pandemic in Populations With Serious Mental Illness
The coronavirus disease 2019 (COVID-19) pandemic will present an unprecedented stressor to patients and health care systems across the globe. Because there is currently no vaccine or treatment for the underlying infection, current health efforts are focused on providing prevention and screening, maintaining continuity of treatment for other chronic conditions, and ensuring access to appropriately intensive services for those with the most severe symptoms.
April 2, 2020
Audio Interview: Lessons from Covid-19 Hotspots
The rapid spread of SARS-CoV-2, a novel coronavirus that emerged in late 2019, and the resulting Covid-19 disease has been labeled a Public Health Emergency of International Concern by the World Health Organization. What physicians need to know about transmission, diagnosis, and treatment is the subject of ongoing updates from infectious disease experts at the Journal.
Governmental Public Health Powers During the COVID-19 Pandemic
The president and all 50 governors have declared health emergencies to counteract the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). While researchers race to develop vaccines, officials are implementing physical distancing, including orders to stay at home, restricting travel, and closing nonessential businesses.
April 1, 2020
Virological assessment of hospitalized patients with COVID-2019
Altogether, this suggests active virus replication in upper respiratory tract tissues, where SARS-CoV is not thought to replicate in spite of detectable ACE-2 expression19,20 . At the same time, the concurrent use of ACE-2 as a receptor by SARS-CoV and SARS-CoV-2 corresponds to a highly similar excretion kinetic in sputum, with active replication in the lung.
An Uncomplicated Delivery in a Patient with Covid-19 in the United States
This case describes uncomplicated labor and vaginal delivery in a woman with Covid-19. Care was taken to avoid infecting hospital staff, and 7 days after the delivery, no caregivers appeared to be infected.
Detection of Covid-19 in Children in Early January 2020 in Wuhan, China
A small number of cases of coronavirus disease 2019 (Covid-19) have been described in children,1,2 and our understanding of the spectrum of illness is limited.3 We conducted a retrospective analysis involving hospitalized children in Wuhan, China.
Rather than stumble through a series of starts and stops and half-measures on both the health and the economic fronts, we should forge a strategy to defeat the coronavirus and open the way to economic revival. If we act immediately, we can make the anniversary of D-Day on June 6, 2020, the day America declares victory over the coronavirus.
Universal Masking in Hospitals in the Covid-19 Era
As the SARS-CoV-2 pandemic continues to explode, hospital systems are scrambling to intensify their measures for protecting patients and health care workers from the virus. An increasing number of frontline providers are wondering whether this effort should include universal use of masks by all health care workers. Universal masking is already standard practice in Hong Kong, Singapore, and other parts of Asia and has recently been adopted by a handful of U.S. hospitals.
March 31, 2020
Based on preliminary U.S. data, persons with underlying health conditions such as diabetes mellitus, chronic lung disease, and cardiovascular disease, appear to be at higher risk for severe COVID-19–associated disease than persons without these conditions.
Safety Recommendations for Evaluation and Surgery of the Head and Neck During the COVID-19 Pandemic
Health care workers who come in close contact with a patient’s head and neck are particularly at risk for developing coronavirus disease 2019 (COVID-19) because of the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) through respiratory droplets. This article provides safety recommendations for these health care workers regarding exams and surgical procedures based on a review of the literature and the experiences of physicians with firsthand knowledge of safety procedures during this pandemic.
Surgical Considerations for Tracheostomy During COVID-19 Pandemic
Lessons learned from the 2003 severe acute respiratory syndrome (SARS) epidemic may help reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), the cause of coronavirus disease 2019 (COVID-19), to health care workers performing open tracheostomies, a surgical procedure to open an airway that may be required for many patients with COVID-19.
Ocular Findings of Patients With COVID-19
One-third of COVID-19 patients from Hubei, China, had ocular manifestations, occurring frequently in patients with more severe physical conditions.
Measures for Care of Cancer Patients During COVID-19 Outbreak in China
The authors describe measures taken to reduce the risk of transmitting severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) to medical staff and cancer patients seeking treatment during the COVID-19 outbreak in China.
Perspectives on COVID-19 Control Measures for Ophthalmology Clinics
This article describes treatment initiatives being undertaken for novel coronavirus 2019 at an ophthalmology center in Singapore.
WHO advises that ivermectin only be used to treat COVID-19 within clinical trials
The current evidence on the use of ivermectin to treat COVID-19 patients is inconclusive. Until more data is available, WHO recommends that the drug only be used within clinical trials.
March 30, 2020
Pharyngeal swabs are widely used to determine the appropriateness of a patient's discharge from the hospital and whether isolation continues to be required. We observed 22 patients who had positive RT-qPCR results for SARS–CoV-2 in the sputum or feces after pharyngeal swabs became negative. These finding raise concern about whether patients with negative pharyngeal swabs are truly virus-free, or sampling of additional body sites is needed.
Covid-19 in Critically Ill Patients in the Seattle Region — Case Series
During the first 3 weeks of the Covid-19 outbreak in the Seattle area, the most common reasons for admission to the ICU were hypoxemic respiratory failure leading to mechanical ventilation, hypotension requiring vasopressor treatment, or both. Mortality among these critically ill patients was high.
Older Clinicians and the Surge in Novel Coronavirus Disease 2019 (COVID-19)
The recent report of 2 critically ill emergency physicians infected by the novel coronavirus disease 2019 (COVID-19) is a sobering reminder of the vulnerability of the nation’s health care workforce.1 While all members of the health care workforce are vital as the health care system faces perhaps its greatest challenge in memory, physicians and nurses are the caregivers who typically have the most direct contact with patients, whether through advising, triaging, or treating those who require hospitalization.
Optimizing the Trade-off Between Learning and Doing in a Pandemic
The world is united regarding the goal of ending the coronavirus disease 2019 (COVID-19) pandemic but not the strategy to achieve that goal. One stark example is the debate over whether to prescribe available therapies, such as quinine-based antimalarial drugs (eg, chloroquine or hydroxychloroquine), or test these drugs in randomized clinical trials (RCTs). At the heart of the problem is one of the oldest dilemmas in human organizations: the “exploitation-exploration” trade-off.
March 27, 2020
Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19)
Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable. Myocardial injury is associated with cardiac dysfunction and arrhythmias. Inflammation may be a potential mechanism for myocardial injury. Aggressive treatment may be considered for patients at high risk of myocardial injury.
Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma
In this uncontrolled case series of 5 critically ill patients with COVID-19 and acute respiratory distress syndrome (ARDS), administration of convalescent plasma containing neutralizing antibody was followed by an improvement in clinical status.
Epidemiology of Covid-19 in a Long-Term Care Facility in King County, Washington
In the context of rapidly escalating Covid-19 outbreaks, proactive steps by long-term care facilities to identify and exclude potentially infected staff and visitors, actively monitor for potentially infected patients, and implement appropriate infection prevention and control measures are needed to prevent the introduction of Covid-19.
March 26, 2020
Cutaneous manifestations in COVID‐19: a first perspective
From the collected data (88 patients), 18 patients (20.4%) developed cutaneous manifestations. 8 patients developed cutaneous involvement at the onset, 10 patients after the hospitalization. Cutaneous manifestations were erythematous rash (14 patients), widespread urticaria (3 patients) and chickenpox-like vesicles (1 patient). Trunk was the main involved region. Itching was low or absent and usually lesions healed in few days. Apparently there was not any correlation with disease’s severity.
Although 2 recent studies1,2 have shown that there were no clinical findings or investigations suggestive of COVID-19 in neonates born to affected mothers, and all samples, including amniotic fluid, cord blood, and breast milk, were negative for SARS-CoV-2, the vertical maternal-fetal transmission cannot be ruled out in the current cohort. Therefore, it is crucial to screen pregnant women and implement strict infection control measures, quarantine of infected mothers, and close monitoring of neonates at risk of COVID-19.
As of March 25, 2020, WHO’s online coronavirus disease 2019 (COVID-19) situation dashboard reveals that the pandemic spans 195 countries and territories with 375 498 cases. With this rapid expansion of the pandemic comes a growing need to ensure that accurate and credible information is accessible to public health authorities, researchers, and the wider public.
March 25, 2020
Our projections show that physical distancing measures were most effective if the staggered return to work was at the beginning of April; this reduced the median number of infections by more than 92% (IQR 66–97) and 24% (13–90) in mid-2020 and end-2020, respectively.
Novel Coronavirus and Old Lessons — Preparing the Health System for the Pandemic
How sad that the people who remember the last major pandemic — influenza in 1968 — are the primary victims of today’s. How sad that despite the many medical advances that have been made since then — critical care, extracorporeal membrane oxygenation (ECMO), emergency medicine, and emergency medical services, to name a few — the treatments offered to many patients in areas where Covid-19 has exploded are the same ones they might have received in that era. Perhaps the lessons they remember, those of quarantine, isolation, and social distancing, are the ones that will save us again.
March 24, 2020
Although many drugs have in vitro activity against different coronaviruses, no clinical evidence currently supports the efficacy and safety of any drug against any coronavirus in humans, including SARS-CoV-2. Numerous drugs that have been highly promising in vitro for other infectious diseases have failed in clinical studies.
Novel 2019 coronavirus SARS-CoV-2 (COVID-19): An updated overview for emergency clinicians
This overview analyzes the best information from the early research, including epidemiologic and demographic features from SARS-CoV-1 and MERS-CoV viruses; lessons learned from the experience of an emergency physician in Northern Italy, where the outbreak has devastated the healthcare system
Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease
Among those with COVID-19, there is a higher prevalence of cardiovascular disease and more than 7% of patients suffer myocardial injury from the infection (22% of the critically ill).
COVID-19: Abnormal Clotting Common in More Severe Disease
Endothelial damage and subsequent clotting is common in severe and critical COVID-19 coronavirus, which may have implications for treatment, Chinese clinicians said at a webinar co-sponsored by the Chinese Cardiovascular Association and American College of Cardiology.
Psychiatrists Anticipate Mental Health Needs With COVID-19
Psychiatric appointments across the country have been going virtual as mental health professionals try to limit potential exposures by moving to home offices and keeping outpatient visits to a minimum.
COVID-19 Update: 17 Days on Surfaces; U.S. 'New Epicenter'? Fatal Chloroquine
March 23, 2020
COVID-19: Melatonin as a potential adjuvant treatment.
This article summarizes the likely benefits of melatonin in the attenuation of COVID-19 based on its putative pathogenesis. The recent outbreak of COVID-19 has become a pandemic with tens of thousands of infected patients. Based on clinical features, pathology, the pathogenesis of acute respiratory disorder induced by either highly homogenous coronaviruses or other pathogens, the evidence suggests that excessive inflammation, oxidation, and an exaggerated immune response very likely contribute to COVID-19 pathology.
These findings suggest that, among Chinese health care workers exposed to COVID-19, women, nurses, those in Wuhan, and front-line health care workers have a high risk of developing unfavorable mental health outcomes and may need psychological support or interventions.
Interventions to mitigate early spread of SARS-CoV-2 in Singapore: a modelling study
Implementing the combined intervention of quarantining infected individuals and their family members, workplace distancing, and school closure once community transmission has been detected could substantially reduce the number of SARS-CoV-2 infections.
Coronavirus in New York - Report From The Front Lines (Video)
Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy
New Guidelines on CPR When COVID-19 Is Known or Suspected
The Toughest Triage — Allocating Ventilators in a Pandemic
Fair Allocation of Scarce Medical Resources in the Time of Covid-19
Public Health Responses to COVID-19 Outbreaks on Cruise Ships — Worldwide, February–March 2020
March 22, 2020
Chloroquine for Coronavirus? Not So Fast
Chloroquine, the old malaria drug, is making news as a potential therapy for coronavirus. Does it belong in the headlines for its antiviral properties, or is it just hype and bluster? Will it become a drug? Let's find out.
Point-of-Care RNA-Based Diagnostic Device for COVID-19
March 21, 2020
Loss of sense of smell as marker of COVID-19 infection
March 20, 2020
LH significantly inhibits the SARS-COV-2 replication, affects virus morphology and exerts anti-inflammatory activity in vitro. These findings indicate that LH protects against the virus attack, making its use a novel strategy for controlling the COVID-19 disease.
People who are at higher risk for severe illness
Telehealth for global emergencies: Implications for coronavirus disease 2019 (COVID-19)
Treatment for severe acute respiratory distress syndrome from COVID-19
COVID-19 and the liver: little cause for concern
Rational use of face masks in the COVID-19 pandemic
COVID-19: protecting health-care workers
Is COVID-19 A Bigger Threat than Flu?
March 19, 2020
A review of the 2019 Novel Coronavirus (COVID-19) based on current evidence
Systematically summarizes the epidemiology, clinical characteristics, diagnosis, treatment and prevention of knowledge surrounding COVID-19.
Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State
Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak
Partha Kar: Covid-19-we must keep faith in our experts
Securing the Safety Net and Protecting Public Health During a Pandemic
Use of antiviral drugs to reduce COVID-19 transmission
Estimation of COVID-19 outbreak size in Italy
Viral dynamics in mild and severe cases of COVID-19
March 18, 2020
A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19
Presidential Powers and Response to COVID-19
March 17, 2020
Updated: WHO Now Doesn't Recommend Avoiding Ibuprofen For COVID-19 Symptoms
Aminoquinolines Against Coronavirus Disease 2019 (COVID-19): Chloroquine or Hydroxychloroquine
Coronavirus Disease 2019 (COVID-19) in Italy
Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1
CDC Expert Answers Top COVID-19 Questions
Clinical course and mortality risk of severe COVID-19
Prevention of SARS-CoV-2 infection in patients with decompensated cirrhosis
COVID-19 in pregnant women – Authors' reply
March 16, 2020
On the front lines of coronavirus: the Italian response to covid-19
Coronavirus Testing – March 16 Q&A with the CDC’s Jay Butler, MD
COVID-19 in Seattle: Clinical Features and Managing the Outbreak
COVID-19: consider cytokine storm syndromes and immunosuppression
COVID-19: the need for continuous medical education and training
March 13, 2020
From Containment to Mitigation of COVID-19 in the US
Coronavirus in Italy – March 13 Q&A with ICU Physician Maurizio Cecconi of Humanitas University JAMA Video Interview
COVID-19, ECMO, and lymphopenia: a word of caution
From Containment to Mitigation of COVID-19 in the US
The Effect of the COVID-19 Pandemic on Clinic Operations
March 12, 2020
Supporting the Health Care Workforce During the COVID-19 Global Epidemic
A comparative study on the clinical features of COVID-19 pneumonia to other pneumonias
March 11, 2020
Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?
Early dynamics of transmission and control of COVID-19: a mathematical modelling study
Detection of SARS-CoV-2 in Different Types of Clinical Specimens
March 4, 2020
March 3, 2020
Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore
Response to COVID-19 in Taiwan: Big Data Analytics, New Technology, and Proactive Testing
Journal Pre Proof
Don't overlook digestive symptoms in patients with 2019 novel coronavirus disease (COVID-19)
Over the course of the current pandemic, it became apparent that some patients can present with abdominal symptoms without fever or respiratory manifestations, and could be overlooked by health care providers.
National Institutes of Health Coronavirus
Coronavirus 2019-nCoV Global Cases by Johns Hopkins CSSE
World Health Organization, Coronavirus
LDH Emergency Order: Face Covering Mandate for Health Care Facilities – April 27, 2021
Health Department confirms two cases of the Brazil COVID-19 variant in Louisiana
J & J Vaccine Information for Clinicians
See important LSU Healthcare Network COVID-19 information and updates, as well as how to request a patient appointment at the buttons below.
COVID-19 Updates Request an Appointment
COVID-19 Vaccines: A Conversation with Nurses Webinar
COVID-19 Research Study
General Information and Guidance
FDA updates on hand sanitizers consumers should not use
FDA continues to find issues with certain hand sanitizer products. FDA test results show certain hand sanitizers have concerningly low levels of ethyl alcohol or isopropyl alcohol, which are active ingredients in hand sanitizer products. The agency urges consumers not to use these subpotent products and has expanded its list to include subpotent hand sanitizers, in addition to hand sanitizers that are or may be contaminated with methanol.
Louisiana Coronavirus (COVID-19) Case Count
Louisiana Department of Health
COVID-19 Vaccination Information
Directives
Allowable Medical, Surgical and Dental Procedures (4/24/20)
Routine, Non-essential Dental Procedures
Louisiana Department of Health COVID-19 Information Updates
Health Alert Network Messages
Health Alert Network Message 22-22: COVID-19 Rebound After Paxlovid Treatment
Health Alert Network Message 22-18: Updated COVID-19 Diagnostic Reporting Requirements
Health Alert Network Message 21-80: WHO Classifies the COVID19 Omicron Variant
Health Alert Network Message 21-78: CDC Approval of Pfizer COVID-19 Vaccine for Children 5-11 Years
Health Alert Network Message 21-72: Louisiana Pfizer-BioNTech COVID-19 Booster Recommendations
Health Alert Network Message 21-55: Temporary Statewide Mask Mandate Guidance for All Business Types
Health Alert Network Message 21-54: COVID-19 Vaccine Storage and Ordering Updates
Health Alert Network Message 21-53: Anti-SARS-CoV-2 Antibody Products
Health Alert Network Message 21-47: Extension of Johnson & Johnson COVID-19 Vaccine Shelf Life
Health Alert Network Message 21-46: COVID-19 Vaccine Pediatric Toolkit for Providers
Health Alert Network Message 21-44: One-Time COVID-19 Provider Vaccine Return Procedure
Health Alert Network Message 20-52: COVID-19 Vaccination Severe/Allergic Reaction Reporting
Health Alert Network Message 20-49: Message on Quarantine Options After Exposure to COVID-19
Health Alert Network Message 20-47: Message on Nursing Home Visitation Related to COVID-19
Health Alert Network Message 20-46: Update COVID-19 Viral Testing Guidance
Health Alert Network Message 20-45: Update: Reporting of COVID-19/SARSCoV-2 Results
Bulletins
Informational Bulletin 20-6: COVID-19 – LMHP Telemedicine/Telehealth
Informational Bulletin 20-5: COVID-19 Provider Update
Informational Bulletin 20-4: COVID-19 – MHR Telemedicine/Telehealth
Press Releases
Louisiana Health Alert Network (LA HAN)--Message on Nursing Home Visitation – November 16, 2020
Louisiana Department of Health adds antigen tests to COVID-19 dashboard – November 13, 2020
Immediate resources from the Office of Behavioral Health – October 8, 2020
Emergency Order: Healthcare Facility Reopening Procedures – October 4, 2020
LSU, LDH community primary care clinic bridges the gap after Hurricane Laura – September 28, 2020
LDH updates methodology for assigning locations to COVID cases, tests – August 25, 2020
Department of Health attributes fourth death to Multisystem Inflammatory Syndrome in Children – August 10, 2020
LDH confirms COVID-19 outbreak connected to Tigerland bars in Baton Rouge
LDH reports 48,515 total COVID-19 cases after removing duplicates and out-of-state residents
Gov. Edwards Announces Louisiana's Roadmap to Resilience Will Start Phase 2 on Friday, June 5
LDH Blog: How one hard-hit state is rallying to support those with addiction amidst COVID-19
Louisiana Department of Health Updates for 5/25/2020
Neighborhood-based COVID-19 testing coming to Northshore parishes
Crisis counseling text line now available to Louisiana residents
Louisiana Department of Health Updates for 5/21/2020
Louisiana Department of Health Updates for 5/18/2020
EMERGENCY ORDER: Continuation of LDH Notices and Orders Due to COVID-19 – May 15, 2020
Louisiana Department of Health Updates for 5/11/2020
Louisiana Department of Health Updates for 5/7/2020
Louisiana Department of Health Updates for 5/6/2020
Louisiana Department of Health Updates for 5/4/2020
Department of Health shares regional data informing decision to extend Stay at Home order -5-1-20
Louisiana Department of Health Updates for 4/29/2020
EMERGENCY ORDER: Continuation of LDH Notices and Orders Due to COVID-19 – April 28, 2020
Louisiana Department of Health Updates for 4/22/2020
Louisiana Department of Health Updates for 4/20/2020 – April 20, 2020
Dr. Courtney N. Phillips joins Louisiana Department of Health as Secretary – April 17, 2020
Louisiana Department of Health Updates for 4/15/2020
Gov. Edwards Issues Statement as Louisiana Surpasses 1,000 COVID-19 Deaths
Louisiana Department of Health Updates for 4/13/2020
Louisiana Department of Health Updates for 4/11/2020
LDH Blog: Public health workers deserve our thanks
Louisiana Department of Health Updates for 4/8/2020
The Department of Health has extended all guidance to April 30, 2020
Louisiana Department of Health Updates for 4/7/2020
Louisiana Department of Health Updates for 4/6/2020
Louisiana Department of Health Updates for 4/1/2020
Louisiana Department of Health Updates for 3/31/2020
Louisiana Department of Health Updates for 3/30/2020
Louisiana Department of Health Updates for 3/29/2020
Louisiana Department of Health Updates for 3/28/2020
Louisiana Department of Health Updates for 3/27/2020
Louisiana Department of Health Updates for 3/26/2020
Louisiana Department of Health Updates for 3/25/2020
Louisiana Department of Health Updates for 3/24/2020
Louisiana Department of Health Updates for 3/23/2020
Louisiana Department of Health Updates for 3/22/2020
Emergency Order: Tattoo/Body Art Closures COVID-19
IEE COMMITTEE CORONAVIRUS RESOURCES
CovidActNow.org was created by a team of data scientists, engineers, and designers in partnership with epidemiologists, public health officials, and political leaders to help understand how the COVID-19 pandemic will affect their region. This tool is built to enable political leaders to quickly make decisions in their Coronavirus response informed by best available data and modeling.
Bill Gates is spending billions to ‘save months’ on a coronavirus vaccine
The Creative Coalition, Association for Healthcare Philanthropy, and the American Hospital Association have united to launch the “Protect the Heroes” campaign, which allows the general public to make direct impact donations to America’s hospital and health systems. Every dollar raised from Protect the Heroes goes directly to the donor’s choice of local hospital to purchase personal protective equipment (PPE) and other support for their local healthcare workers to fight the ravages of COVID-19.
Convalescent plasma transfusion shows promise for severely ill patients with COVID-19
Preliminary research has shown the potential of convalescent plasma therapy to improve clinical outcomes of patients with severe disease related to COVID-19.
Endocrinologists warn of increased COVID-19 complication risks with glucocorticoid use
Adults who are prescribed glucocorticoid therapy for common conditions, such as asthma, allergies and arthritis, as well as individuals with adrenal insufficiency, are at high risk for developing serious complications from COVID-19 due to an inability to mount a normal stress response, according to an editorial published in the Journal of Clinical Endocrinology & Metabolism.\
Medical Companies Win Approval for Rapid Coronavirus Tests
Starting this week, Abbott Laboratories ABT +1.46% plans to make a rapid test available for use in physicians’ offices, urgent-care clinics and other settings through an Abbott device. The test can detect the virus in a patient sample in as few as five minutes and return negative results in 13 minutes.
FDA approved 3 additional kits today (2 PCR, 1 RAPID), 31 March 2020. Total registered COVID-19 Test Kits for commercial use is now 26. Click this link for details.
Johnson & Johnson announces lead COVID-19 vaccine candidate
Johnson & Johnson today announced the selection of a lead COVID-19 vaccine candidate from constructs it had been working on since January 2020, with expected initiation of human clinical studies by September 2020 at the latest.
Q&A: Telepsychiatry plays vital role in combating mental health effects of COVID-19
The novel coronavirus pandemic has led to numerous quarantine and social isolation measures throughout the United States and the world. Thus, psychiatric patients may be unable to attend an in-person appointment with their clinician.
CMS eases requirements for transferring non-COVID-19 infected patients
During a White House Rose Garden event, CMS Administrator Seema Verma unveiled the hospitals without walls program.
"Under the CMS's temporary new rules, hospitals will be able to transfer patients to outside facilities, such as ambulatory surgery centers, inpatient rehabilitation hospitals, hotels, and dormitories, while still receiving hospital payments under Medicare. For example, a healthcare system can use a hotel to take care of patients needing less intensive care while using its inpatient beds for COVID-19 patients," CMS noted in a press release.
Limited testing poses challenges to mapping COVID-19 spread
But how to accurately display and project the spread of the disease has proven difficult, particularly given the limited number of tests available to confirm where cases of COVID-19 actually are.
Coronavirus outbreak: NYU, Chinese researchers develop AI tool to predict severe COVID-19 cases
Researchers have created an artificial intelligence tool that may help physicians predict which patients will develop severe lung disease, even if they initially have a mild case of the novel coronavirus.
In a study published in Computers, Materials & Continua, NYU and Chinese researchers used data from a small group of COVID-19 patients in two Chinese hospitals.They found that patients with mildly elevated liver enzymes and body aches were most likely to develop acute respiratory distress syndrome.
Coronavirus Test Tracker: Commercially Available COVID-19 Diagnostic Tests
As labs and diagnostic developers race to meet demand for assays to detect the SARS-CoV-2 coronavirus, 360Dx is updating this tracker on a regular basis in order to provide readers with up-to-date and accurate information on the regulatory status of these tests in the US, European, and Asian markets.
The tracker includes only those tests that are available for diagnostic use. Links to primary regulatory decisions are provided where available.
AHA launches “100 Million Mask Challenge” to aid front line health professionals
The American Hospital Association (AHA) today announced a national initiative to secure millions of masks for the physicians, nurses and caregivers who are treating coronavirus patients and at greater risk due to a nationwide shortage of personal protective equipment. The effort will facilitate private sector partnerships to address these shortages in the fight against COVID-19.
AHA Urges HHS to Clarify EMTALA, HIPAA Waivers
The AHA March 24 urged the Department of Health and Human Services to clarify the Emergency Medical Treatment and Labor Act and Health Insurance Portability and Accountability Act waivers issued under the public health and national emergency declarations.
AHA Comments to Department of Labor on the Families First Coronavirus Response Act
The AHA has asked the Department of Labor to accurately define "health care provider" as it promulgates regulations implementing key sections of the recently-enacted Families First Coronavirus Response Act and clarify how this policy will be operationalized, including how it interacts with state law.
COVID-19 Drug Therapy –Potential Options
NETEC: Personal Protective Equipment for 2019 Novel Coronavirus (COVID-19)
Information from LabCorp about Coronavirus Disease 2019 (COVID-19)
Quest Diagnostics Testing for COVID-19
Health Articles
Doctors keep discovering new ways the coronavirus attacks the body
Today, there is widespread recognition the novel coronavirus is far more unpredictable than a simple respiratory virus. Often it attacks the lungs, but it can also strike anywhere from the brain to the toes. Many doctors are focused on treating the inflammatory reactions it triggers and its capacity to cause blood clots, even as they struggle to help patients breathe.
As States Rush to Reopen, Scientists Fear a Coronavirus Comeback
Most have not met even minimal criteria for doing so safely, and some are reopening even as coronavirus cases rise, inviting disaster. The much-feared “second wave” of infection may not wait until fall, many scientists say, and instead may become a storm of wavelets breaking unpredictably across the country.
Pharmaceutical giant Pfizer begins testing coronavirus vaccine in people
Pharmaceutical giant Pfizer began testing multiple versions of an experimental coronavirus vaccine in healthy young people in the United States this week, a first step toward establishing the safety, dosage and most promising candidate to take into larger trials that will test effectiveness.
Anti-vaccination leaders seize on coronavirus to push resistance to inoculation
As scientists around the world race to develop a vaccine for the coronavirus, the pandemic is also stoking a surge of activity among activists who argue that such a vaccine must be resisted.
Coronavirus Q&A: Update from the CDC
Anne Schuchat, MD, Principal Deputy Director of the Centers for Disease Control and Prevention (CDC), discusses evolution of CDC guidance and latest developments in the COVID-19 pandemic. Recorded on Friday May 1, 2020.
COVID-19: Anticoagulation Recommended Even After Discharge
Of COVID-19's hallmark symptoms, clotting may not rank high in the national consciousness. But it has made quite an impression in-hospital.
U.S. Coronavirus Death Toll Is Far Higher Than Reported, C.D.C. Data Suggests
Total deaths in seven states that have been hard hit by the coronavirus pandemic are nearly 50 percent higher than normal for the five weeks from March 8 through April 11, according to new death statistics from the Centers for Disease Control and Prevention. That is 9,000 more deaths than were reported as of April 11 in official counts of deaths from the coronavirus.
Young and middle-aged people, barely sick with covid-19, are dying from strokes
Reports of strokes in the young and middle-aged — not just at Mount Sinai, but also in many other hospitals in communities hit hard by the novel coronavirus — are the latest twist in our evolving understanding of the disease it causes. The numbers of those affected are small but nonetheless remarkable because they challenge how doctors understand the virus. Even as it has infected nearly 2.8 million people worldwide and killed about 195,000 as of Friday, its biological mechanisms continue to elude top scientific minds. Once thought to be a pathogen that primarily attacks the lungs, it has turned out to be a much more formidable foe — impacting nearly every major organ system in the body.
In New York’s largest hospital system, many coronavirus patients on ventilators didn’t make it
One other surprising finding from the study was that 70 percent of the patients sick enough to be admitted to the hospital did not have a fever. Fever is listed as the top symptom of covid-19 by the CDC, and for weeks, many testing centers for the virus turned away patients if they did not have one.
A mysterious blood-clotting complication is killing coronavirus patients
One doctor replied that one of his patients had a strange blood problem. Despite being put on anticoagulants, the patient was still developing clots. A second said she’d seen something similar. And a third. Soon, every person on the text chat had reported the same thing.
Chloroquine phosphate, when used without a prescription and supervision of a healthcare provider, can cause serious health consequences, including death. Clinicians and public health officials should discourage the public from misusing non-pharmaceutical chloroquine phosphate (a chemical used in home aquariums). Clinicians should advise patients and the public that chloroquine, and the related compound hydroxychloroquine, should be used only under the supervision of a healthcare provider as prescribed medications.