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Latest Publications and Scientific Information
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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.
Association of BNT162b2 Vaccine Third Dose Receipt With Incidence of SARS-CoV-2 Infection, COVID-19–Related Hospitalization, and Death Among Residents of Long-term Care Facilities, August to October 2021
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.
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.
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.
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.
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
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.
Lab studies identify resistance mutations in SARS-CoV-2’s protease, and some circulating variants have them.
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.
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.
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).
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.
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
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.
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 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.
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
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.
Effect of a 2-week interruption in methotrexate treatment versus continued treatment on COVID-19 booster vaccine immunity in adults with inflammatory conditions (VROOM study): a randomised, open label, superiority trial
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
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
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.
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.
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.
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.
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.
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.
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.
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.
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 (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.
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.
Investigation of the use of a sensor bracelet for the presymptomatic detection of changes in physiological parameters related to COVID-19: an interim analysis of a prospective cohort study (COVI-GAPP)
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).
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
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 18, 2022
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 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.
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.
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.
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
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.
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.
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
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.
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
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.
Fewer people are eligible for the massive studies needed to test treatments for severe COVID-19.
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
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.
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.
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.
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.
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).
Safety and immunogenicity of the FINLAY-FR-1A vaccine in COVID-19 convalescent participants: an open-label phase 2a and double-blind, randomised, placebo-controlled, phase 2b, seamless, clinical trial
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
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.
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.
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.
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.
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.
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).
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
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.
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.
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.
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.
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.
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.
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?
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
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.
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
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.
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.
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.
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.
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.
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.
Real-world effectiveness of molnupiravir and nirmatrelvir/ritonavir against mortality, hospitalization, and in-hospital outcomes among community-dwelling, ambulatory COVID-19 patients during the BA.2.2 wave in Hong Kong: an observational study
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
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.
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).
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.
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.
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 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.
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.
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.
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.
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
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.
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.
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.
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
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
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.\
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
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.
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
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
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
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.
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.
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.
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 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
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
Effectiveness of a COVID-19 Additional Primary or Booster Vaccine Dose in Preventing SARS-CoV-2 Infection Among Nursing Home Residents During Widespread Circulation of the Omicron Variant — United States, February 14–March 27, 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
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
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).
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
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.
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.
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
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.
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.
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.
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
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.
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.
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.
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 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.
Impact of the additional/booster dose of COVID-19 vaccine against severe disease during the epidemic phase characterized by the predominance of the Omicron variant in Italy, November 2021 - March 2022
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.
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.
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.
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.
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
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
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.
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.
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.
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.
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
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.
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.
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.
A single dose of AZD7442 had efficacy for the prevention of Covid-19, without evident safety concerns.
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.
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.
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
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.
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
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
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.
Vaccine effectiveness against SARS-CoV-2 infection and severe outcomes among individuals with immune-mediated inflammatory diseases tested between March 1 and Nov 22, 2021, in Ontario, Canada: a population-based analysis
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.
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
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.
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.
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
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).
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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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
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
Effectiveness of Homologous and Heterologous COVID-19 Booster Doses Following 1 Ad.26.COV2.S (Janssen [Johnson & Johnson]) Vaccine Dose Against COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults — VISION Network, 10 States, December 2021–March 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
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.
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.
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.
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
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
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.
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
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).
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.
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.
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.
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
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.
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
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
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.
The Advisory Committee on Immunization Practices’ Recommendation for Use of Moderna COVID-19 Vaccine in Adults Aged ≥18 Years and Considerations for Extended Intervals for Administration of Primary Series Doses of mRNA COVID-19 Vaccines — United States, February 2022
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 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.
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
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.
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
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
Effectiveness of 2-Dose BNT162b2 (Pfizer BioNTech) mRNA Vaccine in Preventing SARS-CoV-2 Infection Among Children Aged 5–11 Years and Adolescents Aged 12–15 Years — PROTECT Cohort, July 2021–February 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
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
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.
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.
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.
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
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 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.
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
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.
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.
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.
Effectiveness of COVID-19 Pfizer-BioNTech BNT162b2 mRNA Vaccination in Preventing COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Nonimmunocompromised Children and Adolescents Aged 5–17 Years — VISION Network, 10 States, April 2021–January 2022
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%.
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.
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.
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.
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 genomic diversity early in the COVID-19 pandemic points to emergence via repeated zoonotic event.
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.
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.
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
Global, regional, and national minimum estimates of children affected by COVID-19-associated orphanhood and caregiver death, by age and family circumstance up to Oct 31, 2021: an updated modelling study
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
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.
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
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%.
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.
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
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.
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.
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
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.
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.
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.
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.
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
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.
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
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
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.
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
Waning 2-Dose and 3-Dose Effectiveness of mRNA Vaccines Against COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance — VISION Network, 10 States, August 2021–January 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
Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with 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.
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.
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.
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.
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.
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.
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.
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.
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 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.
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
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.
Clinical Characteristics and Outcomes Among Adults Hospitalized with Laboratory-Confirmed SARS-CoV-2 Infection During Periods of B.1.617.2 (Delta) and B.1.1.529 (Omicron) Variant Predominance — One Hospital, California, July 15–September 23, 2021, and December 21, 2021–January 27, 2022
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.
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.
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
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.
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.
Efficacy and safety of baricitinib plus standard of care for the treatment of critically ill hospitalised adults with COVID-19 on invasive mechanical ventilation or extracorporeal membrane oxygenation: an exploratory, randomised, placebo-controlled trial
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
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.
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.
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
SARS-CoV-2 Infection and Hospitalization Among Adults Aged ≥18 Years, by Vaccination Status, Before and During SARS-CoV-2 B.1.1.529 (Omicron) Variant Predominance — Los Angeles County, California, November 7, 2021–January 8, 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.
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.
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.
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.
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.
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.
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).
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
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
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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
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.
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
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
COVID-19 Incidence and Death Rates Among Unvaccinated and Fully Vaccinated Adults with and Without Booster Doses During Periods of Delta and Omicron Variant Emergence — 25 U.S. Jurisdictions, April 4–December 25, 2021
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.
Effectiveness of a Third Dose of mRNA Vaccines Against COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance — VISION Network, 10 States, August 2021–January 2022
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.
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.
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 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.
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.
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.
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
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.
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
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.
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.
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.
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.
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.
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
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.
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.
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.
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
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.
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.
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
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.
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.
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.
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.
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 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.
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.
Here, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.
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.
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 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.
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
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.
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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%).
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
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.
Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with 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.
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.
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.
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.
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
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.
Discovery Health, South Africa’s largest private health insurance administrator, releases at-scale, real-world analysis of Omicron outbreak based on 211 000 COVID-19 test results in South Africa, including collaboration with the South Africa
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.
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
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.
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
Comparative Effectiveness and Antibody Responses to Moderna and Pfizer-BioNTech COVID-19 Vaccines among Hospitalized Veterans — Five Veterans Affairs Medical Centers, United States, February 1–September 30, 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.
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.
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.
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
In this audio interview conducted on December 7, 2021, the editors discuss new studies of the duration of immunity conferred by Covid-19 vaccines.
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
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.
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.
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.
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
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
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.
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.
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
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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
Effectiveness of ChAdOx1 nCoV-19 vaccine against SARS-CoV-2 infection during the delta (B.1.617.2) variant surge in India: a test-negative, case-control study and a mechanistic study of post-vaccination immune responses
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 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
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.
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.
Incidence of SARS-CoV-2 Infection, Emergency Department Visits, and Hospitalizations Because of COVID-19 Among Persons Aged ≥12 Years, by COVID-19 Vaccination Status — Oregon and Washington, July 4–September 25, 2021
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
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.
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.
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.
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.
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.
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.
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.
“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
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.
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
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
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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
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.
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.
Disparities in COVID-19 Vaccination Status, Intent, and Perceived Access for Noninstitutionalized Adults, by Disability Status — National Immunization Survey Adult COVID Module, United States, May 30–June 26, 2021
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.
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 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.
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
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.
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
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.
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.
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
Comparative Effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson & Johnson) Vaccines in Preventing COVID-19 Hospitalizations Among Adults Without Immunocompromising Conditions — United States, March–August 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
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.
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.
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
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.
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 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”).
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
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
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.
Interim Estimates of COVID-19 Vaccine Effectiveness Against COVID-19–Associated Emergency Department or Urgent Care Clinic Encounters and Hospitalizations Among Adults During SARS-CoV-2 B.1.617.2 (Delta) Variant Predominance — Nine States, June–August 2021
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.
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%).
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.
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 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
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.
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.
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.
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
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.
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
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-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
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.
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
Effectiveness of COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Frontline Workers Before and During B.1.617.2 (Delta) Variant Predominance — Eight U.S. Locations, December 2020–August 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.
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
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.
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
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.
Effectiveness of Pfizer-BioNTech and Moderna Vaccines in Preventing SARS-CoV-2 Infection Among Nursing Home Residents Before and During Widespread Circulation of the SARS-CoV-2 B.1.617.2 (Delta) Variant — National Healthcare Safety Network, March 1–August 1, 2021
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.
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.
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.
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.
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.
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.
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.
Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial
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
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.
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
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.
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.
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
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.
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.
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.
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.
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.
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
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.
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.
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.
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
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
Use of COVID-19 Vaccines After Reports of Adverse Events Among Adult Recipients of Janssen (Johnson & Johnson) and mRNA COVID-19 Vaccines (Pfizer-BioNTech and Moderna): Update from the Advisory Committee on Immunization Practices — United States, July 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.
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.
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
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.
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
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.
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 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.
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.
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).
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.
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.
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%.
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
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.
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.
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.
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.
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.
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.
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.
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
Among patients hospitalized with Covid-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than placebo.
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
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.
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 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, 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.
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.
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.
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.
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.
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
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.
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.
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
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.
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.
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
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.
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.
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 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.
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.
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.
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
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
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.
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
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
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.
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
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
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.
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.
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
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.
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.
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.
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.
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.
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.
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
Symptoms of Depression, Anxiety, Post-Traumatic Stress Disorder, and Suicidal Ideation Among State, Tribal, Local, and Territorial Public Health Workers During the COVID-19 Pandemic — United States, March–April 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
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
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.
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
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
Among patients hospitalized with Covid-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than placebo.
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.
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.
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.
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
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
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.
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.
Decreases in COVID-19 Cases, Emergency Department Visits, Hospital Admissions, and Deaths Among Older Adults Following the Introduction of COVID-19 Vaccine — United States, September 6, 2020–May 1, 2021
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.
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.
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.
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.
Ventilation is a key mitigation measure against airborne transmission, and recommendations and funding should be provided to business and schools for assessments and upgrades.
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.
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.
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.
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
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
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.)
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.
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.
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
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
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.
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
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
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.
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).
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.
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
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.
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.
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.
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.
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
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.
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.
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
The safety and immunogenicity profiles of Ad26.COV2.S support further development of this vaccine candidate.
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
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.
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.
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.
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
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.
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
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.
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.
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.
Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data
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.
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.
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.
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.
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).
Ethnic differences in SARS-CoV-2 infection and COVID-19-related hospitalisation, intensive care unit admission, and death in 17 million adults in England: an observational cohort study using the OpenSAFELY platform
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.
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.
Nature wades through the literature on the coronavirus — and summarizes key papers as they appear.
April 29, 2021
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.
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.
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.
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.
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.
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
Updated Recommendations from the Advisory Committee on Immunization Practices for Use of the Janssen (Johnson & Johnson) COVID-19 Vaccine After Reports of Thrombosis with Thrombocytopenia Syndrome Among Vaccine Recipients — United States, April 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.
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.
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.
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
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.)
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 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.
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.
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.
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.
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
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
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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
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.
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.
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.