Covid19-Sources

Preclinical studies of COVID-19 mRNA vaccine BNT162b2, developed by Pfizer and BioNTech, showed reversible hepatic effects in animals that received the BNT162b2 injection. Furthermore, a recent study showed that SARS-CoV-2 RNA can be reverse-transcribed and integrated into the genome of human cells. In this study, we investigated the effect of BNT162b2 on the human liver cell line Huh7 in vitro. Huh7 cells were exposed to BNT162b2, and quantitative PCR was performed on RNA extracted from the cells. We detected high levels of BNT162b2 in Huh7 cells and changes in gene expression of long interspersed nuclear element-1 (LINE-1), which is an endogenous reverse transcriptase. Immunohistochemistry using antibody binding to LINE-1 open reading frame-1 RNA-binding protein (ORFp1) on Huh7 cells treated with BNT162b2 indicated increased nucleus distribution of LINE-1. PCR on genomic DNA of Huh7 cells exposed to BNT162b2 amplified the DNA sequence unique to BNT162b2. Our results indicate a fast up-take of BNT162b2 into human liver cell line Huh7, leading to changes in LINE-1 expression and distribution. We also show that BNT162b2 mRNA is reverse transcribed intracellularly into DNA in as fast as 6 h upon BNT162b2 exposure.

Scientific Reports - Communicate hope to motivate the public during the COVID-19 pandemic

Geographical clustering of the earliest known COVID-19 cases and the proximity of positive environmental samples to live-animal vendors suggest that the Huanan Seafood Wholesale Market in Wuhan was the site of origin of the COVID-19 pandemic.

The newly found Omicron SARS-CoV-2 variant of concern has rapidly spread worldwide. Omicron carries numerous mutations in key regions and is associated with increased transmissibility and immune escape. The variant has recently been divided into four subvariants with substantial genomic differences, in particular between Omicron BA.1 and BA.2. With the surge of Omicron subvariants BA.1 and BA.2, a large number of reinfections from earlier cases has been observed, raising the question of whether BA.2 specifically can escape the natural immunity acquired shortly after a BA.1 infection. To investigate this, we selected a subset of samples from more than 1,8 million cases of infections in the period from November 22, 2021, until February 11, 2022. Here, individuals with two positive samples, more than 20 and less than 60 days apart, were selected. From a total of 187 reinfection cases, we identified 47 instances of BA.2 reinfections shortly after a BA.1 infection, mostly in young unvaccinated individuals with mild disease not resulting in hospitalization or death. In conclusion, we provide evidence that Omicron BA.2 reinfections do occur shortly after BA.1 infections but are rare. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Not applicable ### 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 conducted using data from the Danish COVID-19 surveillance. According to Danish law, ethics approval is not needed for this type of research but approved by the Legal Advisory Board at Statens Serum Institut, a Danish sector research institute under the auspices of the Danish Ministry of Health. The publication only contains aggregated results without personal data. Therefore, the publication is in compliance with the European General Data Protection Regulations. 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 The data are available for research upon reasonable request to the Danish Health Data Authority and Statens Serum Institut and within the framework of the Danish data protection legislation and any required permission from authorities. Consensus genome data from the Danish cases are routinely shared publicly at GISAID (www.gisaid.org), including information on reinfections.

New light is being shed on the colossal human impact of the pandemic, not from government health reports, but from the financial accounts of giant corporations.

Vaccine spike antigen and mRNA persist for two months in lymph node germinal centers...

Autopsies are an important tool in medicine, dissecting disease pathophysiology and causes of death. In COVID-19, autopsies revealed e.g., the effects…

But since I know some folks prefer their evidence in the format of an animated GIF, I'm happy to oblige. Sorry, it lacks the cutesy punch of an out-of-context scene from a Will Ferrell movie, but I'll just have to hope actual scientific evidence is equally entertaining. pic.twitter.com/lZB70oni0O— Dr. Angela Rasmussen (@angie_rasmussen) February 26, 2022

Scientific Reports - Prospective postmortem evaluation of 735 consecutive SARS-CoV-2-associated death cases

A national autopsy registry can provide multicentre quantitative information on COVID-19 deaths on a national level, supporting medical research, political decision-making and public discussion.

Nature - Massive study shows a long-term, substantial rise in risk of cardiovascular disease, including heart attack and stroke, after a SARS-CoV-2 infection.

The aim of this study was to determine clinical outcomes of older patients with coronavirus (COVID-19) who received a combination of vitamin D, magnes…

The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute …

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