Covid19-Sources

Background Protection from SARS-CoV-2 vaccines wanes over time and is compounded by emerging variants including Omicron subvariants. This study evaluated safety and immunogenicity of SARS-CoV-2 variant vaccines. Methods This phase 2 open-label, randomized trial enrolled healthy adults previously vaccinated with a SARS-CoV-2 primary series and a single boost. Eligible participants were randomized to one of six Moderna COVID19 mRNA vaccine arms (50µg dose): Prototype (mRNA-1273), Omicron BA.1+Beta (1 or 2 doses), Omicron BA.1+Delta, Omicron BA.1 monovalent, and Omicron BA.1+Prototype. Neutralization antibody titers (ID50) were assessed for D614G, Delta, Beta and Omicron BA.1 variants and Omicron BA.2.12.1 and BA.4/BA.5 subvariants 15 days after vaccination. Results From March 30 to May 6, 2022, 597 participants were randomized and vaccinated. Median age was 53 years, and 20% had a prior SARS-CoV-2 infection. All vaccines were safe and well-tolerated. Day 15 geometric mean titers (GMT) against D614G were similar across arms and ages, and higher with prior infection. For uninfected participants, Day 15 Omicron BA.1 GMTs were similar across Omicron-containing vaccine arms (3724-4561) and higher than Prototype (1,997 [95%CI:1,482-2,692]). The Omicron BA.1 monovalent and Omicron BA.1+Prototype vaccines induced a geometric mean ratio (GMR) to Prototype for Omicron BA.1 of 2.03 (97.5%CI:1.37-3.00) and 1.56 (97.5%CI:1.06-2.31), respectively. A subset of samples from uninfected participants in four arms were also tested in a different laboratory at Day 15 for neutralizing antibody titers to D614G and Omicron subvariants BA.1, BA.2.12.2 and BA.4/BA.5. Omicron BA.4/BA.5 GMTs were approximately one third BA.1 GMTs (Prototype 517 [95%CI:324-826] vs. 1503 [95%CI:949-2381]; Omicron BA.1+Beta 628 [95%CI:367-1,074] vs. 2125 [95%CI:1139-3965]; Omicron BA.1+Delta 765 [95%CI:443-1,322] vs. 2242 [95%CI:1218-4128] and Omicron BA.1+Prototype 635 [95%CI:447-903] vs. 1972 [95%CI:1337-2907). Conclusions Higher Omicron BA.1 titers were observed with Omicron-containing vaccines compared to Prototype vaccine and titers against Omicron BA.4/BA.5 were lower than against BA.1 for all candidate vaccines. [Clinicaltrials.gov][1] NCT05289037 ### Competing Interest Statement ARB has research grants from Pfizer, Janssen, Merck Sharp and Dohme and CyanVac and serves on the DSMB board for AzurX Biopharma and has served as a consultant for Janssen. ARF has research grants from Pfizer, Janssen, CyanVac, Merck Sharp and Dohme and BioFire Diagnostics and serves on the DSMB for Novavax. EW has research grants from Janssen, Merck Sharp and Dohme and Pfizer and served on a DSMB sponsored by GlaxoSmithKline. NGR has research grants from Pfizer, Sanofi Pasteur, Merck Sharp and serves on the Safety Monitoring Committees for ICON and EMMES. DSG receives consulting fees from Critica, Inc a non-profit organization. LRB has received grant support from NIH for SARS-CoV-2 therapeutic and vaccine development work and is involved in SARS-CoV-2 vaccine trials conducted in collaboration with the NIH, Covid Prevention Network (CoVPN), Crucell/Janssen, Moderna, and Harvard Medical School. SRW has conducted clinical trials funded by Sanofi Pasteur, Janssen Vaccines, ModernaTx, and NIAID/NIH and chairs an Independent Data Monitoring Committee (IDMC) for Janssen Vaccines. CMH is a member of a Safety Monitoring Committee for the Emmes Corporation. SJL has received research grant support to UCSD from Gilead Sciences. Her institution has also received funding from NIH to conduct clinical trials of Janssen and AstraZeneca COVID-19 vaccines. EJA has consulted for Pfizer, Sanofi Pasteur, Janssen, GSK, Moderna, and Medscape, and his institution receives funds to conduct clinical research unrelated to this manuscript from MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Sanofi-Pasteur, Janssen, and Micron. He also serves on data and safety monitoring boards for Kentucky BioProcessing, Inc. and Sanofi Pasteur. He also serves on safety monitoring committees for WCG-ACI Clinical. His institution has also received funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines. The institution for SK has received funding from CDC to conduct clinical research unrelated to this manuscript, from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines, and from Pfizer to conduct clinical trials of Pfizer COVID-19 vaccine. The institution for CAR has received funds to conduct clinical research unrelated to this manuscript from BioFire Inc, GSK, MedImmune, Micron, Janssen, Merck, Novavax, PaxVax, Regeneron, Sanofi-Pasteur. She is co-inventor of patented RSV vaccine technology unrelated to this manuscript, which has been licensed to Meissa Vaccines, Inc. Her institution has received funds from NIH, Moderna, Pfizer, and Janssen to conduct clinical trials of COVID-19 vaccines. EBW has served as an investigator for vaccine studies sponsored by Pfizer, Moderna and Sequiris. He has served on advisory boards for Vaxcyte and Iliad Biotechnologies. MJS has served as an investigator for vaccine studies sponsored by Pfizer, and has received investigator-initiated grants from Merck related to antimicrobial stewardship. RMN has received research grant funding from ModernaTX, Inc and Janssen Vaccines & Prevention B.V. AW has received funding from NIH, GlaxoSmithKline and Sanofi and has been a consultant for Aicuris, X-Vax, Vir, Crozet, and Auritec. ACK reported clinical trials contract funding for vaccines or MAB vs SARS-CoV-2 with Regeneron and Pfizer. AFL has received research grant support to UCSF from Astra Zeneca. The Washington University Clinical Trials Unit has received unrelated funding support in sponsored research agreements from Moderna. PAG receives grant funding from the NIH and is a consultant for Johnson and Johnson. ### Clinical Trial NCT05289037 ### Funding Statement The trial was sponsored and funded by the National Institute of Allergy and Infectious Diseases. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The trial was reviewed and approved by the Advarra central institutional review board which gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: http://Clinicaltrials.gov

Eine vollständige Entwarnung kann Leif Erik Sander für den nahenden Corona-Herbst nicht geben. Das sagt der Impfstoffforscher von der Berliner Charité im RND-Interview. Und erklärt, warum sich Jüngere nicht unbedingt ein viertes Mal gegen Covid-19 impfen lassen müssen.

Der Kinderpneumologe und -kardiologe Dr. Gerald Hofner erzählt im Interview, welche Herausforderungen die Pädiatrie meistern muss, wie er die Corona-Debatte zwischen „Kinderdurchseuchung“ und psychosozialen Folgen erlebt und wie es um die Zukunft von Kinder- und Jugendarztpraxen steht.

Mit den eigenen Waffen schlagen: Die Moleküle der hochansteckenden Omikron-Variante besitzen eine höhere Ladung – das lässt sich auch gegen das Coronavirus verwenden

🚨POST-COVID & Kids🚨New @CDCgov report showing quite clearly that children are at significantly more risk for life-threatening diagnoses after COVID infection. Very convincing evidence that prevention of COVID-19 in children is very important to reduce childhood mortality./1 pic.twitter.com/ntNs5CuQ6d— Tyler Black, MD (@tylerblack32) August 4, 2022

Kids, School, and Suicide=-=-=-=-=-=-=-=-People are asking about the stats I presented about school days being associated with child suicide. There are many ways to look at it.Simply, using July as a reference month, you can easily see "school peaks."It's very striking./1 pic.twitter.com/3CYslprNFP— Tyler Black, MD (@tylerblack32) July 1, 2022

Recently, we reported that BNT162b2-vaccinated individuals after Omicron BA.1 breakthrough infection have strong serum neutralizing activity against Omicron BA.1, BA.2, and previous SARS-CoV-2 variants of concern (VOCs), yet less against the highly contagious Omicron sublineages BA.4 and BA.5 that have displaced previous variants. As the latter sublineages are derived from Omicron BA.2, we characterized serum neutralizing activity of COVID-19 mRNA vaccine triple-immunized individuals who experienced BA.2 breakthrough infection. We demonstrate that sera of these individuals have broadly neutralizing activity against previous VOCs as well as all tested Omicron sublineages, including BA.2 derived variants BA.2.12.1, BA.4/BA.5. Furthermore, applying antibody depletion we showed that neutralization of BA.2 and BA.4/BA.5 sublineages by BA.2 convalescent sera is driven to a significant extent by antibodies targeting the N-terminal domain (NTD) of the spike glycoprotein, whereas their neutralization by Omicron BA.1 convalescent sera depends exclusively on antibodies targeting the receptor binding domain (RBD). These findings suggest that exposure to Omicron BA.2, in contrast to BA.1 spike glycoprotein, triggers significant NTD specific recall responses in vaccinated individuals and thereby enhances the neutralization of BA.4/BA.5 sublineages. Given the current epidemiology with a predominance of BA.2 derived sublineages like BA.4/BA.5 and rapidly ongoing evolution, these findings are of high relevance for the development of Omicron adapted vaccines. ### Competing Interest Statement U.S. and O.T. are management board members and employees at BioNTech SE. A.M., B.G.L., K.K., A.W., M.B., A.F., A.T., and O.O. are employees at BioNTech SE. K.G., S.H. and S.C. are employees at University Hospital, Goethe University Frankfurt. U.G. is an employee at the Health Protection Authority, City of Frankfurt am Main. U.S., O.T. and A.M. are inventors on patents and patent applications related to RNA technology and COVID-19 vaccines. U.S., O.T., A.M., B.G.L., K.K., A.W., M.B., A.F., A.T., and O.O. have securities from BioNTech SE. S.C. has received honorarium for serving on a clinical advisory board for BioNTech.

Since early 2022, Omicron BA.1 has been eclipsed by BA.2, which was in turn outcompeted by BA.5, that displays enhanced antibody escape properties. Here, we evaluated the duration of the neutralizing antibody (Nab) response, up to 16 months after Pfizer BNT162b2 vaccination, in individuals with or without BA.1/BA.2 breakthrough infection. We measured neutralization of the ancestral D614G lineage, Delta and Omicron BA.1, BA.2, BA.5 variants in 291 sera and 35 nasal swabs from 27 individuals. Upon vaccination, serum Nab titers were reduced by 10-, 15-and 25-fold for BA.1, BA.2 and BA.5, respectively, compared with D614G. The duration of neutralization was markedly shortened, from an estimated period of 11.5 months post-boost with D614G to 5.5 months with BA.5. After breakthrough, we observed a sharp increase of Nabs against Omicron subvariants, followed by a plateau and a slow decline after 4-5 months. In nasal swabs, infection, but not vaccination, triggered a strong IgA response and a detectable Omicron neutralizing activity. Thus, BA.5 spread is partly due to abbreviated vaccine efficacy, particularly in individuals who were not infected with previous Omicron variants. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Work in OS lab is funded by: Institut Pasteur Urgence COVID-19 Fundraising Campaign of Institut Pasteur Fondation pour la Recherche Medicale (FRM) ANRS Vaccine Research Institute (ANR10LABX77) Labex IBEID (ANR10LABX62IBEID) ANR/FRM Flash Covid PROTEOSARSCoV2 ANR Coronamito and IDISCOVR. DP is supported by the Vaccine Research Institute. Work in OS lab is funded by: Institut Pasteur INCEPTION program (Investissements Avenir grant ANR16CONV0005) The French Government Investissement Avenir programme Laboratoire Excellence Integrative Biology of Emerging Infectious Diseases (grant no. ANR10LABX62IBEID) NIH PICREID (grant no U01AI151758). The Opera system was cofunded by Institut Pasteur and the Region ile de France (DIM1Health). Work in UPBI is funded by: grant ANR10INSB0401 Region Ile de France program DIM1 Health. The funders of this study had no role in study design data collection and analysis and interpretation or writing of the article. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study [NCT04750720][1] was approved by the Ile de France IV ethical committee. At enrollment, written informed consent was collected and participants completed a questionnaire covering sociodemographic characteristics, virological findings (SARSCoV2 RTqPCR results, date of testing) and data related to SARSCoV2 vaccination (brand product, date of first, second and third vaccination). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the corresponding authors. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04750720&atom=%2Fmedrxiv%2Fearly%2F2022%2F07%2F22%2F2022.07.22.22277885.atom

Nature Medicine - A retrospective analysis of primary care records in the United Kingdom reveals individual symptoms associated with SARS-CoV-2 infections, which persisted for 12 weeks or more...

Nature Biotechnology - Multiple variants of SARS-CoV-2 are inhibited by a trispecific DARPin.

The diagnosis and management of post-acute sequelae of COVID-19 (PASC) poses an ongoing medical challenge. Identifying biomarkers associated with PASC would immensely improve the classification of PASC patients and provide the means to evaluate treatment strategies. We analyzed plasma samples collected from a cohort of PASC and COVID-19 patients (n = 63) to quantify circulating viral antigens and inflammatory markers. Strikingly, we detect SARS-CoV-2 spike antigen in a majority of PASC patients up to 12 months post-diagnosis, suggesting the presence of an active persistent SARS-CoV-2 viral reservoir. Furthermore, temporal antigen profiles for many patients show the presence of spike at multiple time points over several months, highlighting the potential utility of the SARS-CoV-2 full spike protein as a biomarker for PASC. ### Competing Interest Statement David Walt has a financial interest in Quanterix Corporation, a company that develops an ultra-sensitive digital immunoassay platform. He is an inventor of the Simoa technology, a founder of the company and also serves on its Board of Directors. Dr. Walt's interests were reviewed and are managed by Brigham and Women's Hospital and Partners Healthcare in accordance with their conflict of interest policies. ### Funding Statement This study was funded by the Hostetter Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of Massachusetts General Brigham Hospital gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon request to the authors.

The molecular properties of CD8+ T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of 80,000 virus-reactive CD8+ T cells, obtained using a modified antigen-reactive T cell enrichment assay, from 39 patients with COVID-19 and 10 healthy participants. Patients with COVID-19 were segregated into two groups based on whether the dominant CD8+ T cell response to SARS-CoV-2 was “exhausted” or “non-exhausted.” SARS-CoV-2–reactive cells in the exhausted subset were increased in frequency and displayed lesser cytotoxicity and inflammatory features in patients with COVID-19 experiencing mild compared with severe illness. In contrast, SARS-CoV-2–reactive cells in the dominant nonexhausted subset from patients with severe disease showed enrichment of transcripts linked to costimulation, prosurvival NF-κB signaling, and antiapoptotic pathways, suggesting the generation of robust CD8+ T cell memory responses in patients with severe COVID-19 illness. CD8+ T cells reactive to influenza and respiratory syncytial virus from healthy participants displayed polyfunctional features and enhanced glycolysis. Cells with such features were largely absent in SARS-CoV-2–reactive cells from both patients with COVID-19 and healthy controls nonexposed to SARS-CoV-2. Overall, our single-cell analysis revealed substantial diversity in the nature of CD8+ T cells responding to SARS-CoV-2.

This evidence brief includes evidence that has emerged since the previous Public Health Ontario (PHO) BA.4 and BA.5 Evidence and Risk Assessment. 1

Repeated SARS-CoV-2 infections may be prematurely aging human immune systems, research suggests

In order to design actionable SARS-CoV-2 strategies, we extended the SEIRS model to support stratified isolation levels for healthy 60 and vulnerable individuals. At first, we forced isolation levels to be uniform, showing that daily deaths curves of all metropolitan areas in the analysis can be fitted using homogeneous Ro=3.3. In the process, we established the possibility that an extremely short infectiousness period of 2 days coupled with 5 days exposure may be responsible for the multiple deaths valleys observed during the weeks following lockdowns. Regardless of the infectiousness period, we realized that is possible to infer non-uniform isolation levels for healthy 60 and vulnerable by forcing the model to match the 60 to 60 age serology ratio reported in seroprevalence studies. Since the serology ratio is more robust than absolute values, we argue immunity level estimations made in this way (Madrid 43%; Catalonia 24%; Brussels 73%; and Stockholm 65%) are closer to reality. In locations where we didn’t find reliable serology, we performed immunity estimations assuming Spain’s serology ratio (Paris: 24%; London: 34%). We predict that, with the exception of Brussels, no location can return to normal life without having a second wave (albeit in Stockholm a smaller one). For locations far from the herd immunity threshold (HIT) we searched what isolation values allow to return to normal life in 90 days minimizing final deaths, shockingly all found isolations for healthy 60 were negative (i.e. coronavirus parties minimize final deaths). Then, assuming an ideal 1-day long vaccination campaign with a 77% efficacy vaccine, we compared predicted final deaths of those 90-day strategies for all possible vaccination dates with a 180-day long vaccine waiting strategy that imposes 0.40 mandatory isolation to healthy 60 and results in 0.65 isolation to vulnerable. We found that 180-day of mandatory isolations to healthy 60 (i.e. schools and workplaces closed) produces more final deaths if the vaccination date is later than (Madrid: March 7 2021; Catalonia: Dec 26 2020; Paris: Jan 12 2021; London: Jan 25 2021). We conclude that our 2-stratum SEIRS model is suitable to predict SARS-CoV-2 epidemic behavior and can be used to minimize covid-19 disease and isolations related damages.

With reinfections on the rise, scientists warn that each bout increases your risk of troubling outcomes, from long COVID to heart disease.

This cohort study of health care workers in Israel evaluates whether a fourth BNT162b2 vaccine dose lowered breakthrough infection rates of SARS-CoV-2.

Deutsche Forscher haben ein Gen entdeckt, das seine Träger offenbar vor tödlichen Verläufen von Covid-19 schützt. Zehn Prozent der Europäer besitzen GNB3 TT und damit eine stärkere Immunantwort.

Monitoring ambulanter Akut- und Notfälle in Deutschland und aktuelle Aktivität respiratorischer Erkrankungen des Zi.

Background More than two years into the COVID-19 pandemic, it is generally assumed that most of the population has developed anti-SARS-CoV-2 antibodies from infection and/or vaccination. However, public health decision-making is hindered by the lack of up-to-date and precise characterization of the immune landscape in the population. We thus aimed to estimate anti-SARS-CoV-2 antibodies seroprevalence and cross-variant neutralization capacity after Omicron became dominant in Geneva, Switzerland. Methods We conducted a population-based serosurvey between April 29th and June 9th, 2022, recruiting children and adults of all ages from age-stratified random samples of the Geneva general population. Anti-SARS-CoV-2 antibody presence was assessed using commercial immunoassays targeting either the spike (S) or nucleocapsid (N) protein. Antibodies neutralization capacity against different SARS-CoV-2 variants was evaluated using a cell-free Spike trimer-ACE2 binding-based surrogate neutralization assay. Seroprevalence of anti-SARS-CoV-2 antibodies and neutralization capacity were estimated using Bayesian modeling frameworks accounting for the demographics, vaccination, and infection statuses of the Geneva population. Results Among the 2521 individuals included in the analysis (55.2% women; 21.4% aged

Introduction The COVID-19 booster vaccination programme in England used both BNT162b2 and mRNA-1273 vaccines. Direct comparisons of the effectiveness against severe COVID-19 of these two vaccines for boosting have not been made in trials or observational data. Methods On behalf of NHS England, we used the OpenSAFELY-TPP database to match adult recipients of each vaccine type on date of vaccination, primary vaccine course, age, and other characteristics. Recipients were eligible if boosted between 29 October 2021 and 31 January 2022, and followed up for 12 weeks. Outcomes were positive SARS-CoV-2 test, COVID-19 hospitalisation, and COVID-19 death. We estimated the cumulative incidence of each outcome, and quantified comparative effectiveness using risk differences (RD) and hazard ratios (HRs). Results 1,528,431 people were matched in each group, contributing a total 23,150,504 person-weeks of follow-up. The 12-week risks per 1,000 people of positive SARS-CoV-2 test were 103.2 (95%CI 102.4 to 104.0) for BNT162b2 and 96.0 (95.2 to 96.8) for mRNA-1273: the HR comparing mRNA-1273 with BNT162b2 was 0.92 (95%CI 0.91 to 0.92). For COVID-19 hospitalisations the 12-week risks per 1,000 were 0.65 (95%CI 0.56 to 0.75) and 0.44 (0.36 to 0.54): HR 0.67 (95%CI 0.58 to 0.78). COVID-19 deaths were rare: the 12-week risks per 1,000 were 0.03 (95%CI 0.02 to 0.06) and 0.01 (0.01 to 0.02): HR 1.23 (95%CI 0.59 to 2.56). Comparative effectiveness was generally similar within subgroups. Conclusion Booster vaccination with mRNA-1273 COVID-19 vaccine was more effective than BNT162b2 in preventing SARS-CoV-2 infection and COVID-19 hospitalisation during the first 12 weeks after vaccination. ### Competing Interest Statement BG's work on better use of data in healthcare more broadly is currently funded in part by: the Bennett Foundation, the Wellcome Trust, NIHR Oxford Biomedical Research Centre, NIHR Applied Research Collaboration Oxford and Thames Valley, the Mohn-Westlake Foundation; all Bennett Institute staff are supported by BG's grants on this work. EW holds grants from MRC. RHK was funded by UK Research and Innovation (Future Leaders Fellowship MR/S017968/1). ### Funding Statement This work was jointly funded by UKRI [COV0076;MR/V015737/1], the Longitudinal Health and Wellbeing strand of the National Core Studies programme (MC\_PC\_20030; MC\_PC\_20059; COV-LT-0009), NIHR and Asthma UK-BLF. The OpenSAFELY data science platform is funded by the Wellcome Trust (222097/Z/20/Z). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Health Research Authority (REC reference 20/LO/0651) and by the London School of Hygiene and Tropical Medicine Ethics Board (reference 21863). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Detailed pseudonymised patient data is potentially re-identifiable and therefore not shared. All study code is available for inspection and re-use at https://github.com/opensafely/comparative-booster

Objective To examine infants in Scotland aged 0-27 days with confirmed SARS-CoV-2 infection; the risk of neonatal infection by factors including maternal infection status and gestation at birth; and the need for hospital admission among infected neonates. Design Population-based cohort study. Setting and population All live births in Scotland, 1 March 2020 to 31 January 2022. Results There were 141 neonates with confirmed SARS-CoV-2 infection over the study period, giving an overall infection rate of 153 per 100,000 live births (141/92,009). Among infants born to women with confirmed infection around the time of birth, the infection rate was 1,811 per 100,000 live births (15/828). Nearly two-thirds (92/141, 65.2%) of babies with confirmed neonatal infection had an associated admission to neonatal or (more commonly) paediatric care. Of those admitted to hospital, 6/92 (6.5%) infants were admitted to neonatal or paediatric intensive care, however none of these six had COVID-19 recorded as the main diagnosis underlying their admission. There were no neonatal deaths among babies with confirmed infection. Implications and relevance Confirmed neonatal SARS-CoV-2 infection is uncommon. Secular trends in the neonatal infection rate broadly follow those seen in the general population, albeit at a lower level. Maternal infection at birth increases the risk of neonatal infection, but most babies with neonatal infection are born to women without confirmed infection. A high proportion of neonates with confirmed infection are admitted to hospital, with resulting implications for the baby, family, and services, although their outcomes are generally good. ### Competing Interest Statement CG and JK are lead investigators for the British Paediatric Surveillance Unit study Neonatal complications of COVID-19 and co-investigators for the SARS-CoV-2 infection in neonates or in pregnancy: outcomes at 18 months (SINEPOST) study. The other authors declare no competing interests. ### Funding Statement COPS is a sub-study of EAVE II which is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE - The Health Data Research Hub for Respiratory Health [MC\_PC\_19004] which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through Public Health Scotland and Scottish Government DG Health and Social Care and the Data and Connectivity National Core Study led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation. COPS has received additional funding from Tommys charity and support from Sands charity. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: COPS has ethical approval from the National Research Ethics Service Committee, South East Scotland 02 (REC 12/SS/0201: SA 2) and information governance approval from the Public Benefit and Privacy Panel for Health and Social Care (2021-0116). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Patient-level data underlying this article cannot be shared publicly due to data protection and confidentiality requirements. Data access for approved researchers can be authorised by the Public Benefit and Privacy Panel for Health and Social Care (https://www.informationgovernance.scot.nhs.uk/pbpphsc/). Enquiries regarding data availability should be directed to phs.edris@phs.scot.

Facemasks have become a symbol of disease prevention in the context of COVID-19; yet, there still exists a paucity of collected scientific evidence surrounding their epidemiological efficacy in the prevention of SARS-CoV-2 transmission. This systematic review sought to analyze the efficacy of facemasks, regardless of type, on the prevention of SARS-CoV-2 transmission in both healthcare and community settings. The initial review yielded 1732 studies, which were reviewed by three study team members. Sixty-one full text studies were found to meet entry criteria, and 13 studies yielded data that was used in the final analysis. In all, 243 subjects were infected with COVID-19, of whom 97 had been wearing masks and 146 had not. The probability of getting COVID-19 for mask wearers was 7% (97/1463, p=0.002), for non-mask wearers, probability was 52% (158/303, p=0.94). The Relative Risk of getting COVID-19 for mask wearers was 0.13 (95% CI: 0.10-0.16). Based on these results, we determined that across healthcare and community settings, those who wore masks were less likely to contact COVID-19. Future investigations are warranted as more information becomes available. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript.

Healing the sick, not cutting taxes, must be the priority In his final speeches as prime minister, Boris Johnson listed seemingly endless achievements. Prominent among them was the claim that more people are in work now than before the pandemic. Yet any employers listening may have struggled to reconcile that with their frantic search for people to harvest crops, serve in hotels and restaurants, provide health and social care, and ensure that transport hubs can operate. Front page pictures in newspapers of long queues at airports and crops rotting in fields painted a different picture. The explanation for this apparent paradox was simple. The prime minister’s claim, like so many he has made, was false. The independent fact checking organisation Full Fact provided the true figures in April 2022: the workforce actually had 600 000 fewer workers than before the pandemic. Full Fact noted with disappointment that Johnson had, by then, made this claim nine times in parliament without correcting the record.1 Yet despite formal complaints from official statisticians,23 he remains undeterred …

Among unvaccinated pregnant women, SARS-CoV-2 infection during the Delta wave, in comparison to the pre-Delta period, was associated with increased requirement for oxygen support (including ECMO) and higher maternal mortality. Disease severity and pregnancy complications were similar between the Omi …

This is the eighth update alert for a living rapid review (1) on the use of masks for the prevention of respiratory virus infections, including SARS-CoV-2, in health care and community settings. The first 3 updates (2–4) were monthly, after which the interval was switched to bimonthly (5, 6). Beginning in June 2021, the interval was extended to biannually. For this update, searches were done from 3 December 2021 to 2 June 2022 using the same search methods as the original review. Inclusion was restricted to randomized trials and observational studies that controlled for confounders. Non–peer-reviewed studies were excluded unless they were based on data collected after February 2021 to capture evidence on mask use in the B.1.617.2 (Delta) and B.1.1.529 (Omicron) variant predominant periods. The update searches identified 1592 citations. No new randomized controlled trials (RCTs) and 5 new observational studies on the association of mask use and SARS-CoV-2 infection met inclusion criteria (Supplement Table 1). Three studies were done in community settings (7–9), and 2 studies (10, 11) were done in health care settings. One preprint study (9) of mask use in community settings collected data during Delta and Omicron predominant periods; the other studies were done before the emergence of these variants. All studies had methodological limitations, including unclear or low participation rate, potential recall bias, and failure to report attrition or missing data (Supplement Table 2).

New research to be presented at this year's European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2022, Lisbon, 23–26 April) suggests that many of the symptoms connected to post-COVID ...

Studies have demonstrated a potential correlation between low vitamin D status and both an increased risk of infection with SARS-CoV-2 and poorer clinical outcomes. This retrospective study examines if, and to what degree, a relationship exists between ...

A randomized controlled trial of calcifediol (25-hydroxyvitamin D3) as a treatment for hospitalized COVID-19 patients in Córdoba, Spain, found that the treatment was associated with reduced ICU admissions with very large effect size and high statistical significance, but the study has had limited impact because it had only 76 patients and imperfect blinding, and did not measure vitamin D levels pre- and post-treatment or adjust for several comorbidities. Here we reanalyze the reported results of the study using rigorous and well established statistical techniques, and find that the randomization, large effect size, and high statistical significance address many of these concerns. We show that random assignment of patients to treatment and control groups is highly unlikely to distribute comorbidities or other prognostic indicators sufficiently unevenly to account for the large effect size. We also show that imperfect blinding would need to have had an implausibly large effect to account for the reported results. Finally, comparison with two additional randomized clinical trials of vitamin D supplementation for COVID-19 in India and Brazil indicates that early intervention and rapid absorption may be crucial for the observed benefits of vitamin D. We conclude that the Córdoba study provides sufficient evidence to warrant immediate, well-designed pivotal clinical trials of early calcifediol administration in a broader cohort of inpatients and outpatients with COVID-19. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement No funding was received. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Since this was a reanalysis of published information, no IRB or oversight board was involved. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data is included in the paper.

Convalescent human-derived SARS-CoV-2 RBD and NTD antibodies mediated neutralization as well as infection enhancement in vitro, yet infusion of these antibodies in mice or cynomolgus macaques resulted in suppression of virus replication.