Covid19-Sources

Objectives  To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect. Design  Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials. Data sources  Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015. Eligibility criteria for study selection  Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome. Results  25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity

Nature - Immunity acquired through previous infection is less effective against Omicron than against other variants, but the risk of severe COVID-19 remains low.

Monoclonal antibody therapy for the treatment of SARS-CoV-2 infection has been highly successful in decreasing disease severity; however, the recent emergence of the heavily mutated Omicron variant has posed a challenge to this treatment strategy. The Omicron variant BA.1 has been found to evade neutralization by the Regeneron and Eli Lilly therapeutic monoclonal antibodies, while Sotrovimab and the Evusheld monoclonal antibody cocktail retain significant neutralizing activity. A newly emerged variant, Omicron BA.2, containing the BA.1 mutations plus an additional 6 mutations and 3 deletions, 3 of which lie in the receptor binding domain, has been found to be spreading with increased transmissibility. We report here, using a spike protein-pseudotyped lentivirus assay, that Omicron BA.2 is not neutralized with detectable titer by any of the therapeutic monoclonal antibodies, including Sotrovimab and the Evusheld monoclonal antibodies. The results demonstrate the difficulty of identifying broadly neutralizing monoclonal antibodies against SARS-CoV-2 and the importance of the T cell response from which immunoevasion is more difficult. ### Competing Interest Statement The authors have declared no competing interest.

There has been much discussion on the general principle of "naturally-acquired” immunity arising from recovery from SARS CoV 2infection, and this recovery state contributing to the prevalence of immunity to reinfection, often referred to as Herd Immunity. This has led to the belief that hospit...

Autopsies of deceased with a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can provide important insights into the novel disease and its course. Furthermore, autopsies are essential for the correct statistical recording of the coronavirus disease 2019 (COVID-19) deaths. In the northern German Federal State of Hamburg, all deaths of Hamburg citizens with ante- or postmortem PCR-confirmed SARS-CoV-2 infection have been autopsied since the outbreak of the pandemic in Germany. Our evaluation provides a systematic overview of the first 80 consecutive full autopsies. A proposal for the categorisation of deaths with SARS-CoV-2 infection is presented (category 1: definite COVID-19 death; category 2: probable COVID-19 death; category 3: possible COVID-19 death with an equal alternative cause of death; category 4: SARS- CoV-2 detection with cause of death not associated to COVID-19). In six cases, SARS-CoV-2 infection was diagnosed post- mortem by a positive PCR test in a nasopharyngeal or lung tissue swab. In the other 74 cases, SARS-CoV-2 infection had already been known antemortem. The deceased were aged between 52 and 96 years (average 79.2 years, median 82.4 years). In the study cohort, 34 deceased were female (38%) and 46 male (62%). Overall, 38% of the deceased were overweight or obese. All deceased, except for two women, in whom no significant pre-existing conditions were found autoptically, had relevant comor- bidities (in descending order of frequency): (1) diseases of the cardiovascular system, (2) lung diseases, (3) central nervous system diseases, (4) kidney diseases, and (5) diabetes mellitus. A total of 76 cases (95%) were classified as COVID-19 deaths, corresponding to categories 1–3. Four deaths (5%) were defined as non-COVID-19 deaths with virus-independent causes of death. In eight cases, pneumonia was combined with a fulminant pulmonary artery embolism. Peripheral pulmonary artery embolisms were found in nine other cases. Overall, deep vein thrombosis has been found in 40% of the cases. This study provides the largest overview of autopsies of SARS-CoV-2-infected patients presented so far.

This descriptive study compares the effect of mRNA-based COVID-19 vaccination with BNT162b2 (Pfizer-BioNTech) vs mRNA-1273 (Moderna) on the reported cases of myocarditis in the US after each vaccination dose.

Although much has been published since the first cases of COVID-19, there remain unanswered questions regarding SARS-CoV-2 impact on testes and the potential consequences for reproductive health. We investigated testicular alterations in deceased COVID-19-patients, the precise location of the virus, its replicative activity, and the molecules involved in the pathogenesis. We found that SARS-CoV-2 testicular tropism is higher than previously thought and that reliable viral detection in the testis requires sensitive nanosensoring or RT-qPCR using a specific methodology. Macrophages and spermatogonial cells are the main SARS-CoV-2 lodging sites and where new virions form inside the Endoplasmic Reticulum Golgi Intermediate Complex. Moreover, we showed infiltrative infected monocytes migrating into the testicular parenchyma. SARS-CoV-2 maintains its replicative and infective abilities long after the patient infection, suggesting that the testes may serve as a viral sanctuary. Further, infected testes show thickening of the tunica propria, germ cell apoptosis, Sertoli cell barrier loss, evident hemorrhage, angiogenesis, Leydig cell inhibition, inflammation, and fibrosis. Finally, our findings indicate that high angiotensin II levels and activation of mast cells and macrophages may be critical for testicular pathogenesis. Importantly, our data suggest that patients who become critically ill exhibit severe damages and may harbor the active virus in testes. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was primarily financed by Ferring COVID19 Investigational Grant (grant FIN0042393, to G.M.J.C). G.M.J.C. also received resources from FAPEMIG (APQ0107821). Other specific grants from coauthors punctually helped in some experiments and logistics of the present study. A.F.V. was supported by a FAPESP (grant #18/176470) when the study was conducted. G.R.F.C. is supported by a FAPESP (grant #20/074190). M.H.F. was supported by the Laboratorio Sao Paulo/BH/MG. M.L.N. is supported by FAPESP (grant # 2019/072509 and #2020/048360) and CNPq. F.G.F. received grants from FAPEMIG (CBBAPQ0308117, and CBBAPQ0429517), and from Rede Mineira de Pesquisa e Inovacao para Bioengenharia de Nanossistemas (RM PIBEM FAPEMIG TEC RED0028216). R.S.A was supported by CNPq (R.S.A.: 312688/20172 and 439119/20189). ### 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 Research Ethics Committee of the Mater Dei Hospital and the National Research Ethics Committee (CONEP) approved this investigation under the number CAAE: 30999320.1.0000.5128. Testicular fragments were obtained after the study was approved by the Ethics Committee in Research of the Universidade Federal de Minas Gerais COEP/UFMG (COEP ETIC 104 n117/07) 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

Importance: Despite widespread vaccination against COVID-19 in the United States, there are limited empirical data quantifying the public health impact in the population. Objective: To estimate the number of cases of COVID-19 averted due to COVID-19 vaccination Design, Setting, and Participants: The California Department of Public Health (CDPH) provided person-level data on COVID-19 cases and COVID-19 vaccine administration. To estimate the number of COVID-19 cases that would have occurred in the vaccine era in absence of vaccination, we applied a statistical model that estimated the relationship of COVID-19 cases in the pre-vaccine era between the unvaccinated age group (

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. ### Competing Interest Statement K.S.C. is an inventor on U.S. Patent No. 10,960,070 B2 and International Patent Application No. WO/2018/081318 entitled: Prefusion Coronavirus Spike Proteins and Their Use. K.S.C. is an inventor on U.S. Patent Application No. 62/972,886 entitled: 2019-nCoV Vaccine. L.W., W.S., J.R.M., M.R., N.J.S. and D.C.D are inventors on U.S. Patent Application No. 63/147,419 entitled: Antibodies Targeting the Spike Protein of Coronaviruses. L.P., A.V.R., B.N., D.V., A.C., A.D., K.S., H.A. and M.G.L. are employees of Bioqual. K.S.C, L.W. and W.S. are inventors on multiple U.S. Patent Applications entitled Anti-Coronavirus Antibodies and Methods of Use. A.C. and D.K.E. are employees of Moderna. M.S.S. serves on the scientific board of advisors for Moderna and Ocugen. The other authors declare no competing interests.

New: Assessment of an Omicron-specific booster vs Moderna original (vs ancestral) booster in macaques: no difference"An Omicron boost may not provide greater immunity or protection compared to a boost with the current mRNA-1273 vaccine"https://t.co/9lonQjawcj pic.twitter.com/wGq6WCLdIx— Eric Topol (@EricTopol) February 4, 2022

People with long Covid face an uphill battle convincing skeptics their malady is real – but discrediting uncommon conditions is hardly a new phenomenon

OBJECTIVE. The aim of this study was to investigate the incidence of type 1 diabetes in children and adolescents during the coronavirus disease 2019 (COVID-19)

Severe infection with severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is characterized by massive cytokine release and T cell loss. The exaggerated host immune response, incapable of viral clearance, instead aggravates respiratory distress, as well as cardiac, and/or damage to other organ …

Recently Csabai et al.1 have found a most likely contaminated metagenomic sample set from Antarctica that contained traces of unique SARS-CoV-2 variants. This is a short followup of that report where we attempt to find genetic footprint of the hosts. With reasonable confidence we could identif...

European Journal of Epidemiology - Determine age-specific infection fatality rates for COVID-19 to inform public health policies and communications that help protect vulnerable age groups. Studies...

AbstractBackground. Most of the millions of people that are vaccinated against SARS-CoV-2, the causative agent of COVID-19, have previously been infected by rel

Drei Fragen aus dem Forum. Eine Telepolis-Kolumne

Eine Studie der US-Gesundheitsbehörde CDC belege, dass 81,8 Prozent der früh gegen Covid-19 geimpften Schwangeren eine Fehlgeburt erleiden. Das stimmt nicht

This study investigates the immunogenicity of extended mRNA vaccine dosing intervals.

INFECTION INSIGHTS - Findings from the UK’s world-leading human challenge study provide new insights into mild infections with SARS-CoV-2 in healthy young adults.

Patients with COVID-19 may develop abnormal inflammatory response and lymphopenia, followed in some cases by delayed-onset syndromes, often long-lasting after the initial SARS-CoV-2 infection. As viral infections may activate human endogenous retroviral elements (HERV), we studied the effect of SARS-CoV-2 on HERV-W and HERV-K envelope (ENV) expression, known to be involved in immunological and neurological pathogenesis of human diseases. Our results have showed that the exposure to SARS-CoV-2 virus activates early HERV-W and K transcription but only HERV-W ENV protein expression, in an infection- and ACE2-independent way within peripheral blood mononuclear cell cultures from one-third of healthy donors. Moreover, HERV-W ENV protein was significantly increased in serum and plasma of COVID-19 patients, correlating with its expression in CD3+ lymphocytes and with disease severity. Finally, HERV-W ENV was found expressed in post-mortem tissues of lungs, heart, brain olfactory bulb and nasal mucosa from acute COVID-19 patients in cell-types relevant for COVID-19-associated pathogenesis within affected organs, but different from those expressing of SARS-CoV-2 antigens. Altogether, the present study revealed that SARS-CoV-2 can induce HERV-W ENV expression in cells from individuals with symptomatic and severe COVID-19. Our data suggest that HERV-W ENV is likely to be involved in pathogenic features underlying symptoms of acute and post-acute COVID. It highlights the importance to further understand patients’ genetic susceptibility to HERV-W activation and the relevance of this pathogenic element as a prognostic marker and a therapeutic target in COVID-19 associated syndromes. ![Figure][1] ### Competing Interest Statement HP, BC, JB, JP, NQ received compensation for their work from Geneuro Innovation (France) ### Funding Statement This study was funded by the french National Agency for Researsch (ANR) - program RA-COVID-19 V15 (project name : COVERI) ### 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 SECRETARIA DE SALUD INSTITUTO NACIONAL DE ENFERMEDADES RESPIRATORIAS ISMAEL COSIO VILLEGAS (MEXICO)gave ethical approval for this work - Ethics committee/IRB of HOSPICES CIVILS DE LYON (HCL)/ BIOBANK OF CROIX ROUSSE HOSPITAL (FRANCE) gave ethical approval for this work - Ethics committee/IRB of SERVICIOS CIENTIFICO TECNICOS - SERVICIO DE BIOBANCO (BSSA)OF UNIVERSITY OF SARAGOZA (SPAIN) 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 work are contained in the manuscript [1]: pending:yes

To overcome pandemics, such as COVID-19, vaccines are urgently needed at very high volumes. Here we assess the techno-economic feasibility of producing RNA vaccines for the demand associated with a global vaccination campaign. Production process performance ...

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) causes severe acute respiratory syndrome. mRNA vaccines directed at the SARS-CoV-2 spike protein resulted in development of Abs and protective immunity. To determine the mechanism, we analyzed the kinetics of induction of circulating

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 third-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 lower after infection compared with 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 postvaccination 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 with vaccination.

Shi Zhengli has spent years at the Wuhan Institute of Virology researching coronaviruses that live in bats. Her work has come under fire as the world tries to understand where covid-19 came from.

The novel coronavirus, or SARS-CoV-2, which causes the highly contagious COVID-19, has infected millions of people worldwide.

Virus-like particle (VLP) and live virus assays were used to investigate neutralizing immunity to Delta and Omicron SARS-CoV-2 variants in 239 samples from 125 fully vaccinated individuals. In uninfected, non-boosted individuals, VLP neutralization titers to Delta and Omicron were reduced 2.7-fold and 15.4-fold, respectively, compared to wild-type (WT), while boosted individuals (n=23) had 18-fold increased titers. Delta breakthrough infections (n=39) had 57-fold and 3.1-fold titers whereas Omicron breakthrough infections (n=14) had 5.8-fold and 0.32-fold titers compared to uninfected non-boosted and boosted individuals, respectively. The difference in titers (p=0.049) was related to a higher proportion of moderate to severe infections in the Delta cohort (p=0.014). Correlation of neutralizing and spike quantitative antibody titers was decreased with Delta or Omicron compared to WT. Neutralizing antibodies in Delta and Omicron breakthrough infections increase overall, but the relative magnitude of increase is greater in more clinically severe infection and against the specific infecting variant. ### Competing Interest Statement C.Y.C. is the director of the UCSF-Abbott Viral Diagnostics and Discovery and receives research support for SARS-CoV-2 studies from Abbott Laboratories. The other authors declare no competing interests. ### Funding Statement This work was funded by US CDC Epidemiology and Laboratory Capacity (ELC) for Infectious Diseases Grant 6NU50CK000539 to the California Department of Public Health (COVIDnet) (M-K.M., C.H., D.A.W., C.Y.C.), the Innovative Genomics Institute (IGI) at UC Berkeley and UC San Francisco (J.D., M.O., C.Y.C.), US Centers for Disease Control and Prevention contract 75D30121C10991 (C.Y.C.), the Roddenberry Foundation (M.O.), National Institutes of Health (NIH) grants R37AI083139 (M.O.), R21AI59666 (J.A.D.), and U54HL147127 (M.M.K.), the Howard Hughes Medical Institute (J.A.D.), the Gladstone Institutes (J.A.D. and M.O.), Abbott Laboratories (C.Y.C.), and the Sandler Program for Breakthrough Biomedical Research (C.Y.C.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The findings and conclusions in this article are those of the author(s) and do not necessarily represent the views or opinions of the California Department of Public Health or the California Health and Human Services Agency. ### 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: Institutional Review Board of UCSF gave ethical approval for this work Details in manuscript: Blood samples were collected through two methods. First, remnant whole blood and plasma samples from patients hospitalized with COVID-19 at UCSF were retrieved from UCSF Clinical Laboratories daily based on availability. Remnant samples were biobanked and retrospective medical chart reviews for relevant demographic and clinical metadata were performed under a waiver of consent and according to protocols approved by the UCSF Institutional Review Board (protocol numbers 10-01116 and 11-05519). Samples were obtained from pediatric and adult patients of all genders. No analyses based on sex or age were conducted. Second, plasma samples were also collected through the UMPIRE (UCSF EMPloyee and community member Immune REsponse) study, a longitudinal COVID-19 research study focused on collection of prospective whole blood and plasma samples from enrolled subjects to evaluate the immune response to vaccination, with and without boosting, and/or vaccine breakthrough infection. Informed consent for participation in the UMPIRE study and collection of data and samples were obtained according to a protocol approved by the UCSF Institutional Review Board (protocol number 20-33083). 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.

This report describes how children and adolescents were more likely to receive a new diabetes diagnosis after infection with SARS-CoV-2, the virus that causes COVID-19.

Nature Communications - To monitor the presence of novel SARS-CoV-2 variants in New York City, Smyth et al. perform deep-sequencing of the receptor binding domain of S protein in wastewater samples...