Covid19-Sources

AbstractBackground. Long COVID is defined as the persistence of symptoms beyond 3 months after SARS-CoV-2 infection. To better understand the long-term course a

Moderna geht mit dem weltweit ersten mRNA-Impfstoff gegen eine Infektion mit Influenzaviren an den Start. Das Biotechnologieunternehmen teilt mit, den Impfstoff im Rahmen von Studien zum ersten Mal an Menschen zu testen.

The Origins of SARS-CoV-2: A Critical Review Holmes et al. Since the first reports of a novel SARS-like coronavirus in December 2019 in Wuhan, China, there has been intense interest in understanding how SARS-CoV-2 emerged in the human population. Recent debate has coalesced around two competing ideas: a “laboratory escape” scenario and zoonotic emergence. Here, we critically review the current scientific evidence that may help clarify the origin of SARS-CoV-2.

The SARS-CoV-2 B.1.617.2 Variant of Concern (VOC), first detected in India, is now dominant in the UK, having rapidly1 displaced the B.1.1.7 strain2 that emerged in the UK with the second COVID-19 wave in late 2020. The efficacy of currently licensed COVID-19 vaccines against B.1.617.2 is unknown; although it possesses 12 mutations in its spike protein relative to the wildtype SARS-CoV-2 first detected in Wuhan, China, in December, 2019, B.1.617.2 lacks mutations at amino acid positions 501 or 484 in its ACE2 receptor-binding domain, commonly associated with VOCs (appendix p 2) or escape from neutralising antibodies (NAbs).

Eine Impfung, die in der Nasenschleimhaut wirkt, könnte Impfdurchbrüche vermeiden – ist aber kompliziert

Variants of SARS-CoV-2 are evolving under acombination of immune selective pressure in infected hosts and natural genetic drift, raising a global alarm regarding the durability of COVID-19 vaccines. Here, we conducted longitudinal analysis over 1.8 million SARS-CoV-2 genomes from 183 countries or territories to capture vaccination-associated viral evolutionary patterns. To augment this macroscale analysis, we performed viral genome sequencing in 23 vaccine breakthrough COVID-19 patients and30 unvaccinated COVID-19 patientsfor whom we also conducted machine-augmented curation of the electronic health records (EHRs). Strikingly, we find the diversity of the SARS-CoV-2 lineages is declining at the country-level with increased rate of mass vaccination (n = 25 countries, mean correlation coefficient = -0.72, S.D. = 0.20). Given that the COVID-19 vaccines leverage B-cell and T-cell epitopes, analysis of mutation rates shows neutralizing B-cell epitopes to be particularly more mutated than comparable amino acid clusters (4.3-fold, p < 0.001). Prospective validation of these macroscale evolutionary patternsusing clinically annotated SARS-CoV-2 whole genome sequences confirms that vaccine breakthrough patients indeed harbor viruses with significantly lower diversity in known B cell epitopes compared to unvaccinated COVID-19 patients (2.3-fold, 95% C.I. 1.4-3.7). Incidentally, in these study cohorts, vaccinated breakthrough patients also displayed fewer COVID-associated complications and pre-existing conditions relative to unvaccinated COVID-19 patients. This study presents the first known evidence that COVID-19 vaccines are fundamentally restricting the evolutionary and antigenic escape pathways accessible to SARS-CoV-2. The societal benefit of mass vaccination may consequently go far beyond the widely reported mitigation of SARS-CoV-2 infection risk and amelioration of community transmission, to include stemming of rampant viral evolution.

The choice is between vaccinating or eventually getting infected.

Die dritte Welle der Corona-Pandemie gilt als gebrochen – seit Ende April 2021 sind die Zahlen deutlich rückläufig. Forschende des Fraunhofer ITWM haben mit Hilfe der EpideMSE-Software mathematisch analysiert, welche Auswirkungen unterschiedliche Maßnahmen bei der Pandemiebekämpfung hatten. Dabei erweisen sich Massentests als besonders wirksam.

Jung J, et al. Infect Chemother. 2021 Jun;53(2):332-341. https://doi.org/10.3947/ic.2021.0046

Objectives To estimate the effectiveness of BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and ChAdOx1 (AstraZeneca) vaccines against symptomatic SARS-CoV-2 infection and severe outcomes (COVID-19 hospitalization or death) caused by the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) variants of concern (VOCs) during December 2020 to May 2021. Methods We conducted a test-negative design study using linked population-wide vaccination, laboratory testing, and health administrative databases in Ontario, Canada. Results Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination (≥14 days after dose 1) was higher for mRNA-1273 than BNT162b2 and ChAdOx1. Full vaccination (≥7 days after dose 2) increased vaccine effectiveness for BNT162b2 and mRNA-1273 against Alpha. Protection against symptomatic infection caused by Beta/Gamma was lower with partial vaccination for ChAdOx1 than mRNA-1273. Against Delta, vaccine effectiveness after partial vaccination tended to be lower than against Alpha for BNT162b2 and mRNA-1273, but was similar to Alpha for ChAdOx1. Full vaccination with BNT162b2 increased protection against Delta to levels comparable to Alpha and Beta/Gamma. Vaccine effectiveness against hospitalization or death caused by all studied VOCs was generally higher than for symptomatic infection after partial vaccination with all three vaccines. Conclusions Our findings suggest that even a single dose of these 3 vaccine products provide good to excellent protection against symptomatic infection and severe outcomes caused by the 4 currently circulating variants of concern, and that 2 doses are likely to provide even higher protection. ### Competing Interest Statement KW is CEO of CANImmunize and serves on the data safety board for the Medicago COVID-19 vaccine trial. The other authors declare no conflicts of interest. ### Funding Statement This work was supported by the Canadian Immunization Research Network (CIRN) through a grant from the Public Health Agency of Canada and the Canadian Institutes of Health Research (CNF 151944). This project was also supported by funding from the Public Health Agency of Canada, through the Vaccine Surveillance Reference group and the COVID-19 Immunity Task Force. This study was also supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH). JCK is supported by Clinician-Scientist Award from the University of Toronto Department of Family and Community Medicine. PCA is supported by a Mid-Career Investigator Award from the Heart and Stroke 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: ICES is a prescribed entity under Ontarios Personal Health Information Protection Act (PHIPA). Section 45 of PHIPA authorizes ICES to collect personal health information, without consent, for the purpose of analysis or compiling statistical information with respect to the management of, evaluation or monitoring of, the allocation of resources to or planning for all or part of the health system. Projects that use data collected by ICES under section 45 of PHIPA, and use no other data, are exempt from REB review. The use of the data in this project is authorized under section 45 and approved by ICES Privacy and Legal Office. 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 The dataset from this study is held securely in coded form at ICES. While legal data sharing agreements between ICES and data providers (e.g., healthcare organizations and government) prohibit ICES from making the dataset publicly available, access may be granted to those who meet pre-specified criteria for confidential access, available at www.ices.on.ca/DAS (email: das@ices.on.ca). The full dataset creation plan and underlying analytic code are available from the authors upon request, understanding that the computer programs may rely upon coding templates or macros that are unique to ICES and are therefore either inaccessible or may require modification.

Objectives The primary hypothesis was that the risk of incident or repeat psychiatric illness, fatigue and sleep problems increased following COVID-19 infection. The analysis plan was pre-registered (). Design Matched cohorts were assembled using a UK primary care registry (the CPRD-Aurum database). Patients were followed-up for up to 10 months, from 1st February 2020 to 9th December 2020. Setting Primary care database of 11,923,499 adults (≥16 years). Participants From 232,780 adults with a positive COVID-19 test (after excluding those with

Jetzt mal ein Thread warum es aus fachlicher Sicht keine Begründung für eine FFP2-Masken-Pflicht gibt....und dies nach meiner fachlichen Bewertung von jedem Gericht gekippt werden müsste.— David Weissflog (@infect_prevent) January 18, 2021

Background Data on long-term outcomes of hospitalized COVID-19 patients are scarce. Objective To provide a detailed account of hospitalized COVID-19 patients until 180 days after their initial hospitalization. Design Nationwide cohort study using claims data from the German Local Health Care Funds, the health insurer of one-third of the German population. Setting Germany. Patients Adult patients hospitalized in Germany between Feb 1 and April 30, 2020 with PCR-confirmed COVID-19 and a related principal diagnosis. Measurements Patient characteristics and ventilation status, in-hospital, 30-,...

Ever since the COVID-19 pandemic began and antivaxxers made common cause with COVID-19 cranks, deniers, and conspiracy theorists, I've been repeating a simple message: Everything old is new again. The

A third shot of the vaccine lifted immune response in volunteers who had already received two.

New research suggests that a coronavirus infection alters the biomechanical properties of red and white blood cells, in some cases for months -- a possible explanation for long COVID.

Auch wenn im Moment der weitere Verlauf sehr schwer abzuschätzen ist: Für die nächsten 4-6 Wochen sieht es aus der Sicht meiner Modelle ganz gut aus für uns in Deutschland. Die täglichen Zahlen fie…

Original Article from The New England Journal of Medicine — Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine

Myocarditis 101With recent reports of myocarditis after vaccination in young people after the mRNA vaccines, it is worthwhile to reexamine the risk/benefit ratio of these vaccines in this population

Background: The impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective cohort study, we compared outcomes of pati

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing Corona Virus Disease-2019 (COVID-19), affects the pulmonary systems via angiotensin-converting enzyme-2 (ACE-2) receptor being an entry to systemic infection. As COVID-19 disease features ACE-2 deficiency, a link to microcirculation is proposed. OCT-angiography (OCT-A) enables non-invasive analysis of retinal microvasculature. Thus, an impaired systemic microcirculation might be mapped on retinal capillary system. As recent OCT-A studies, analyzing microcirculation in two subdivided layers, yielded contrary results, an increased subdivision of retinal microvasculature might offer an even more fine analysis. The aim of the study was to investigate retinal microcirculation by OCT-A after COVID-19 infection in three subdivided layers (I). In addition, short-term retinal affections were monitored during COVID-19 disease (II). Considering (I), a prospective study (33 patientspost-COVID, 28 controls) was done. Macula and peripapillary vessel density (VD) were scanned with the Spectralis II. Macula VD was measured in three layers: superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Analysis was done by the EA-Tool, including an Anatomical Positioning System and an analysis of peripapillary VD by implementing BMO landmarks. Overall, circular (c1, c2, c3) and sectorial VD (s1-s12) were analyzed. Considering (II), a retrospective study of 29 patients with severe ...

The journal retracts the article, The Safety of COVID-19 Vaccinations—We Should Rethink the Policy [...]

Eine Analyse von Daten des israelischen Gesundheitsministeriums führt in die Irre. Die Impfung senkt das Risiko, an Covid-19 zu sterben.

A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429), originally detected in California, carries spike glycoprotein mutations S13I in the signal peptide, W152C in the N-terminal domain (NTD), and L452R in the receptor-binding domain (RBD). Plasma from individuals vaccinated with a Wuhan-1 isolate-based mRNA vaccine or convalescent individuals exhibited neutralizing titers, which were reduced 2-3.5 fold against the B.1.427/B.1.429 variant relative to wildtype pseudoviruses. The L452R mutation reduced neutralizing activity of 14 out of 34 RBD-specific monoclonal antibodies (mAbs). The S13I and W152C mutations resulted in total loss of neutralization for 10 out of 10 NTD-specific mAbs since the NTD antigenic supersite was remodeled by a shift of the signal peptide cleavage site and formation of a new disulphide bond, as revealed by mass spectrometry and structural studies.

Objective to assess reactogenicity and immunogenicity of heterologous prime-boost immunisations of ChAdOx1-nCoV19 (Vaxzevria, ChAdOx) followed by BNT162b2 (Comirnaty, BNT) compared to homologous BNT/BNT immunisation. Design prospective, observational cohort study. Setting unicenter study in a cohort of health care workers at a tertiary care center in Berlin, Germany. Participants 340 health care workers immunised between 27 December 2020 and 21 May 2021 at Charité - Universitätsmedizin Berlin, Germany Main outcome measures the main outcomes were reactogenicity assessed on days one, three, five and seven post prime and boost vaccination, and immunogenicity measured by serum SARS-CoV-2 full spike-, spike S1-, and spike RBD-IgG, virus neutralisation capacity, anti-S1-IgG avidity, and T cell reactivity measured by Interferon gamma release assay at 3-4 weeks post prime and boost immunisation. Results Heterologous ChAdOx/BNT booster vaccination was overall well-tolerated and reactogenicity was largely comparable to homologous BNT/BNT vaccination. Systemic reactions were most frequent after prime immunisation with ChAdOx (86%, 95CI: 79-91), and less frequent after homologous BNT/BNT (65%, 95CI: 56-72), or heterologous ChAdOx/BNT booster vaccination (48%, 95CI: 36-59). Serum antibody responses and T cell reactivity were strongly increased after both homologous and heterologous boost, and immunogenicity was overall robust, and comparable between both regimens in this cohort, with slightly increased S1-IgG avidity and T cell responses following heterologous booster immunisation. Conclusions Evidence of rare thrombotic events associated with ChAdOx has led to recommendation of a heterologous booster with mRNA vaccines for certain age groups in several European countries, despite a lack of robust safety and immunogenicity data for this vaccine regimen. This interim analysis provides evidence that the currently recommended heterologous ChAdOx/BNT immunisation regimen with 10-12 week vaccine intervals is well tolerated and slightly more immunogenic compared to homologous BNT/BNT vaccination with three week vaccine intervals. Heterologous prime-boost immunisation for COVID-19 may be generally applicable to optimise logistics and improve immunogenicity and to mitigate potential intermittent supply shortages for individual vaccines. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial EudraCT-No. 2021-001512-28 ### Funding Statement Supported by the German Federal Ministry of Education and Research (BMBF) Forschungsnetzwerk der Universitaetsmedizin zu Covid-19 COVIM - FKZ: 01KX2021 (to L.E.S., V.M.C., F.K., C.D., N.S.). ### 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: EICOV was approved by the ethics committee (IRB) of Charite - Universitaetsmedizin Berlin (EA4/245/20) and COVIM (EudraCT-No. 2021-001512-28) was approved by the Federal Institute for Vaccines and Biomedicines (Paul Ehrlich Institute) and by the Ethics committee of the state of Berlin. 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 Data is available upon reasonable request.

Three regional groups with different dynamics and different degrees of effectiveness of the applied measures were identified. The partial shutdown was moderately effective and at most stopped the exponential growth, but the spread remained partly plateau-like and regionally continued to grow in a nearly linear fashion. Only the extended shutdown reversed the linear growth.

Background: Identifying areas that pose the greatest risk for community transmission of COVID-19 is essential to direct public health action and allow safe re-o

Severe COVID-19 patients show various immunological abnormalities including T-cell reduction and cytokine release syndrome, which can be fatal and is a major concern of the pandemic. However, it is poorly understood how T-cell dysregulation can contribute to the pathogenesis of severe COVID-19. Here we show single cell-level mechanisms for T-cell dysregulation in severe COVID-19, demonstrating new pathogenetic mechanisms of T-cell activation and differentiation underlying severe COVID-19. By in silico sorting CD4+ T-cells from a single cell RNA-seq dataset, we found that CD4+ T-cells were highly activated and showed unique differentiation pathways in the lung of severe COVID-19 patients. Notably, those T-cells in severe COVID-19 patients highly expressed immunoregulatory receptors and CD25, whilst repressing the expression of FOXP3. Furthermore, we show that CD25+ hyperactivated T-cells differentiate into multiple helper T-cell lineages, showing multifaceted effector T-cells with Th1 and Th2 characteristics. Lastly, we show that CD25-expressing hyperactivated T-cells produce the protease Furin, which facilitates the viral entry of SARS-CoV-2. Collectively, CD4+ T-cells from severe COVID-19 patients are hyperactivated and FOXP3-mediated negative feedback mechanisms are impaired in the lung, which may promote immunopathology. Therefore, our study proposes a new model of T-cell hyperactivation and paralysis that drives immunopathology in severe COVID-19.