Covid19-Sources

Our findings suggest that a third dose of the BNT162b2 mRNA vaccine is effective in protecting individuals against severe COVID-19-related outcomes, compared with receiving only two doses at least 5 months ago.

The worldwide outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Alongside vaccines, antiviral therapeutics are an important part of the healthcare response to counter the ongoing threat presented by COVID-19. Here, we report the discovery and characterization of PF-07321332, an orally bioavailable SARS-CoV-2 main protease inhibitor with in vitro pan-human coronavirus antiviral activity and excellent off-target selectivity and in vivo safety profiles. PF-07321332 has demonstrated oral activity in a mouse-adapted SARS-CoV-2 model and has achieved oral plasma concentrations exceeding the in vitro antiviral cell potency in a phase I clinical trial in healthy human participants.

Pfizer’s is the second pill to show effectiveness against Covid-19, and it is the first purpose-built to attack the virus that causes the disease.

Myocarditis in Kindern & Jugendlichen #COVID19 Erkrankung vs #Impfung Ein paar Gedanken dazu - Herzmuskel-, Herzbeutelentzündungen (Myokarditis, Pericarditis) finden sich gehäuft in jungen Männern mit Beginn der Pubertät. 1/n https://t.co/lulmTB47bH

The Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has outcompeted previously prevalent variants and become a dominant strain worldwide. We report the structure, function, and antigenicity of its full-length spike (S) trimer and those of the Gamma and Kappa variants and compare their characteristics with the G614, Alpha, and Beta variants. Delta S can fuse membranes more efficiently at low levels of cellular receptor ACE2, and its pseudotyped viruses infect target cells substantially faster than the other five variants, possibly accounting for its heightened transmissibility. Each variant shows different rearrangement of the antigenic surface of the N-terminal domain of the S protein, but only causes local changes in the receptor-binding domain (RBD), making the RBD a better target for therapeutic antibodies.

Research conducted since the start of the pandemic is starting to suggest that the mouth could be a key player in COVID-19 infection.

Background Critically ill patients diagnosed with COVID-19 may develop a pro-thrombotic state that places them at a dramatically increased lethal risk. Although platelet activation is critical for thrombosis and is responsible for the thrombotic events and cardiovascular complications, the role of platelets in the pathogenesis of COVID-19 remains unclear. Methods Using platelets from healthy volunteers, non-COVID-19 and COVID-19 patients, as well as wild-type and hACE2 transgenic mice, we evaluated the changes in platelet and coagulation parameters in COVID-19 patients. We investigated ACE2 expression and direct effect of SARS-CoV-2 virus on platelets by RT-PCR, flow cytometry, Western blot, immunofluorescence, and platelet functional studies in vitro, FeCl3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo. Results We demonstrated that COVID-19 patients present with increased mean platelet volume (MPV) and platelet hyperactivity, which correlated with a decrease in overall platelet count. Detectable SARS-CoV-2 RNA in the blood stream was associated with platelet hyperactivity in critically ill patients. Platelets expressed ACE2, a host cell receptor for SARS-CoV-2, and TMPRSS2, a serine protease for Spike protein priming. SARS-CoV-2 and its Spike protein directly enhanced platelet activation such as platelet aggregation, PAC-1 binding, CD62P expression, α granule secretion, dense granule release, platelet spreading, and clot retraction in vitro, and thereby Spike protein enhanced thrombosis formation in wild-type mice transfused with hACE2 transgenic platelets, but this was not observed in animals transfused with wild-type platelets in vivo. Further, we provided evidence suggesting that the MAPK pathway, downstream of ACE2, mediates the potentiating role of SARS-CoV-2 on platelet activation, and that platelet ACE2 expression decreases following SARS-COV-2 stimulation. SARS-CoV-2 and its Spike protein directly stimulated platelets to facilitate the release of coagulation factors, the secretion of inflammatory factors, and the formation of leukocyte–platelet aggregates. Recombinant human ACE2 protein and anti-Spike monoclonal antibody could inhibit SARS-CoV-2 Spike protein-induced platelet activation. Conclusions Our findings uncovered a novel function of SARS-CoV-2 on platelet activation via binding of Spike to ACE2. SARS-CoV-2-induced platelet activation may participate in thrombus formation and inflammatory responses in COVID-19 patients.

Read the latest article version by Andreas Martin Lisewski, at F1000Research.

Covid-19 Impfdurchbruch Kennzahlen basierend auf Wochenberichten des RKI.

Background Vaccination has proven effective against infection with SARS-CoV-2, as well as death and hospitalisation following COVID-19 illness. However, little is known about the effect of vaccination on other acute and post-acute outcomes of COVID-19. Methods Data were obtained from the TriNetX electronic health records network (over 81 million patients mostly in the USA). Using a retrospective cohort study and time-to-event analysis, we compared the incidences of COVID-19 outcomes between individuals who received a COVID-19 vaccine (approved for use in the USA) at least 2 weeks before SARS-CoV-2 infection and propensity score-matched individuals unvaccinated for COVID-19 but who had received an influenza vaccine. Outcomes were ICD-10 codes representing documented COVID-19 sequelae in the 6 months after a confirmed SARS-CoV-2 infection (recorded between January 1 and August 31, 2021). Associations with the number of vaccine doses (1 vs. 2) and age ( 60 vs. ≥ 60 years-old) were assessed. Results Among 10,024 vaccinated individuals with SARS-CoV-2 infection, 9479 were matched to unvaccinated controls. Receiving at least one COVID-19 vaccine dose was associated with a significantly lower risk of respiratory failure, ICU admission, intubation/ventilation, hypoxaemia, oxygen requirement, hypercoagulopathy/venous thromboembolism, seizures, psychotic disorder, and hair loss (each as composite endpoints with death to account for competing risks; HR 0.70-0.83, Bonferroni-corrected p.05), but not other outcomes, including long-COVID features, renal disease, mood, anxiety, and sleep disorders. Receiving 2 vaccine doses was associated with lower risks for most outcomes. Associations between prior vaccination and outcomes of SARS-CoV-2 infection were marked in those 60 years-old, whereas no robust associations were observed in those ≥ 60 years-old. Conclusions COVID-19 vaccination is associated with lower risk of several, but not all, COVID-19 sequelae in those with breakthrough SARS-CoV-2 infection. These benefits of vaccination were clear in younger people but not in the over-60s. The findings may inform service planning, contribute to forecasting public health impacts of vaccination programmes, and highlight the need to identify additional interventions for COVID-19 sequelae. Funding National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Work supported by the National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre (grant BRC-1215-20005). MT is an NIHR Academic Clinical Fellow and NIHR Oxford Health BRC Senior Research Fellow. The views expressed are those of the authors and not necessarily those of the UK National Health Service, NIHR, or the UK Department of Health. The funding source had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. ### 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: Data de-identification is attested to through a formal determination by a qualified expert as defined in Section 164.514(b)(1) of the HIPAA Privacy Rule. This formal determination supersedes TriNetX's waiver from the Western Institutional Review Board (IRB). 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 TriNetX system returned the results of these analyses as csv files which were downloaded and archived. Data presented in this paper and the Appendix can be freely accessed at [URL to be added on publication]. Additionally, TriNetX will grant access to researchers if they have a specific concern (via the third-party agreement option).

Am Sonntag, 31. Oktober 2021, gab es in Baden-Württemberg weitere 1.612 bestätigte Infektionen mit dem Coronavirus und 5 weitere COVID-19-Todesfälle. Die landesweite 7-Tage-Inzidenz liegt bei 195,7. Es gilt die Basisstufe.

Woher stammt das Coronavirus? Aus der Natur oder aus einem Forschungslabor? Auf Einladung des Wissenschaftsmagazin "Science" diskutierten nun vier Experten mit unterschiedlichen Ansichten die Ursprungstheorien. Thematisiert wurden dabei auch neue Studien und neu aufgetauchte Dokumente.

The first line of defense against SARS-CoV-2 is the upper respiratory tract, yet we know little about the amount, type, and kinetics of mucosal anti-Spike antibodies (Ab) in response to intramuscular (i.m.) COVID-19 vaccination. We analyzed salivary Ab against SARS-CoV-2 Spike following mRNA/mRNA and adenovirus (Ad)/mRNA regimes. While anti-Spike/RBD IgG was detected in the saliva and correlated with the systemic response, anti-Spike/RBD IgA associated with the secretory component (sIgA) was also detected, and did not necessarily correlate with serum Ab. Only modest levels of neutralizing capacity were observed in saliva at 2 weeks post-dose 2, and by 6 months, anti-Spike/RBD IgG were greatly diminished. In contrast, low levels of anti-Spike sIgA persisted up to 6 months after dose 2. Our results show that SARS-CoV-2 vaccination induces an IgG response in the saliva that decays over time and an sIgA response that does not necessarily correlate with systemic immunity. One-Sentence Summary Our study delves into how intra-muscular mRNA/mRNA or mRNA/Ad COVID-19 vaccination regimes confer immunity in the oral cavity with important implications for understanding protection against breakthrough infections in healthy vaccinated people. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by an Ontario Together province of Ontario grant to JG and ACG and a Foundation grant from the Canadian Institutes of Health Research to JG (Fund #15992). Funding for the LTCH cohort was provided through a Canada COVID-19 Immunity Task force grant (to SS, AM, MO, ACG and JG). Funding for initial development of the assays in the Gingras lab was provided through generous donations from the Royal Bank of Canada (RBC) and the Krembil Foundation to the Sinai Health System Foundation. The robotics equipment used is housed in the Network Biology Collaborative Centre at the Lunenfeld-Tanenbaum Research Institute, a facility supported by Canada Foundation for Innovation funding, by the Ontarian Government and by Genome Canada and Ontario Genomics (OGI-139). ### 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 Mount Sinai Hospital Research Ethics Board (REB) granted approval for recruiting staff in long-term care facilities located in the Greater Toronto Area for blood and saliva collection and for conducting serum ELISAs at the Lunenfeld-Tanenbaum Research Institute (study number: 20-0339-E). The University of Toronto REB granted approval for subject recruitment to collect blood and saliva samples and for conducting saliva ELISAs (study number: 23901). The University of Saskatchewan REB granted approval for saliva sample collection during the pre-COVID era (study number: BIO-USask-1579). 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 data will be available upon reasonable request.

#CoronaInfo – Eine wichtige Frage bei der Corona-Impfung ist: macht sie genügend Immunität in Nase/Hals, um das Virus dort gleich nach der Ansteckung zu stoppen? Zwei Studien, hier zusammengefasst, haben dafür Corona-Antikörper im Speichel gemessen. … (1/7)

Cell Discovery - <ArticleTitle Language="En" xml:lang="en">Comprehensive investigations revealed consistent pathophysiological alterations after...

Nisreen A Alwan questions whether the current rates of covid infection in UK school children are acceptable when we have emerging evidence of the virus's lingering health effects I recently wrote on Twitter1 in reference to the current SARS-CoV-2 child infection rates in England: “It really isn’t fair how covid is allowed to spread so uncontrollably in school-aged kids. I feel like a broken record, but I can’t stop saying this. Kids paid such a high price to protect the adults in the first year of the pandemic and now the adults don’t seem to care. Not fair.” Childism is a term that has been used to describe institutional prejudice and systemic injustice against children,2 as observed during the pandemic in policy decisions. Adami and Dineen critique the language that describes children as “vectors of transmission,” as well as the effect of school closures, and policies that exacerbate child hunger and compromise their safety. I’d argue that allowing mass SARS-CoV-2 infections among children is also a form of childism. The latest data from the Office for National Statistics (ONS) on infection prevalence in England3 show that 7.8% of secondary school aged children (school year 7 to 11) and 3.8% of those aged 2 to school year 6 …

Fast Deterministic Selection Andrei Alexandrescu The D Language Foundation Abstract The selection problem, in forms such as finding the median or choosing the k top ranked items in a dataset, is a core task in computing with numerous applications in fields as diverse as statistics, databases, Machine Learning, finance, biology, and graphics. The selection algorithm Median of Medians, although a landmark theoretical achievement, is seldom used in practice be- cause it is slower than simple approaches based on sampling. The main contribution of this paper is a fast linear-time deterministic selection algorithm MedianOfNinthers based on a refined definition of MedianOfMedians. A complementary algorithm MedianOfExtrema is also pro- posed. These algorithms work together to solve the selection problem in guaranteed linear time, faster than state-of-the-art baselines, and without resorting to randomization, heuristics, or fall- back approaches for pathological cases. We demonstrate results on uniformly distributed random numbers, typical low-entropy artificial datasets, and real-world data.

Background: Whether vaccine effectiveness against Coronavirus disease 2019 (Covid-19) lasts longer than 6 months is unclear.brbrMethods: A retrospective coh

⚠️BREAKING—REINFECTION & NATURAL IMMUNITY—new CDC study in hospitalized adults finds: unvaccinated people with prior #COVID19 infection recently were **5 times more likely** to be reinfected / get breakthrough versus people recently fully vaccinated! 🧵 https://t.co/VGmWPmm5lE https://t.co/mlt5fJ3643

Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) today announced topline results from a Phase 3 randomized, controlled trial evaluating the effi

Comirnaty and Spikevax: EMA recommendations on extra doses boosters

This report describes mRNA COVID-19 vaccine recipients as having greater immunity from COVID-19 infection than previously infected, unvaccinated persons.

Background. Vaccination has proven effective against infection with SARS-CoV-2, as well as death and hospitalisation following COVID-19 illness. However, little is known about the effect of vaccination on other acute and post-acute outcomes of COVID-19. Methods. Data were obtained from the TriNetX electronic health records network (over 81 million patients mostly in the USA). Using a retrospective cohort study and time-to-event analysis, we compared the incidences of COVID-19 outcomes between individuals who received a COVID-19 vaccine (approved for use in the USA) at least 2 weeks before SARS-CoV-2 infection and propensity score-matched individuals unvaccinated for COVID-19 but who had received an influenza vaccine. Outcomes were ICD-10 codes representing documented COVID-19 sequelae in the 6 months after a confirmed SARS-CoV-2 infection (recorded between January 1 and August 31, 2021). Associations with the number of vaccine doses (1 vs. 2) and age ( 60 vs. ≥ 60 years-old) were assessed. Findings. Among 10,024 vaccinated individuals with SARS-CoV-2 infection, 9479 were matched to unvaccinated controls. Receiving at least one COVID-19 vaccine dose was associated with a significantly lower risk of respiratory failure, ICU admission, intubation/ventilation, hypoxaemia, oxygen requirement, hypercoagulopathy/venous thromboembolism, seizures, psychotic disorder, and hair loss (each as composite endpoints with death to account for competing risks; HR 0.70-0.83, Bonferroni-corrected p.05), but not other outcomes, including long-COVID features, renal disease, mood, anxiety, and sleep disorders. Receiving 2 vaccine doses was associated with lower risks for most outcomes. Associations between prior vaccination and outcomes of SARS-CoV-2 infection were marked in those 60 years-old, whereas no robust associations were observed in those ≥ 60 years-old. Interpretation. COVID-19 vaccination is associated with lower risk of several, but not all, COVID-19 sequelae in those with breakthrough SARS-CoV-2 infection. These benefits of vaccination were clear in younger people but not in the over-60s. The findings may inform service planning, contribute to forecasting public health impacts of vaccination programmes, and highlight the need to identify additional interventions for COVID-19 sequelae. Funding. National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Work supported by the National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre (grant BRC-1215-20005). MT is an NIHR Academic Clinical Fellow and NIHR Oxford Health BRC Senior Research Fellow. The views expressed are those of the authors and not necessarily those of the UK National Health Service, NIHR, or the UK Department of Health. The funding source had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. ### 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: Data de-identification is attested to through a formal determination by a qualified expert as defined in Section 164.514(b)(1) of the HIPAA Privacy Rule. This formal determination supersedes TriNetX's waiver from the Western Institutional Review Board (IRB). 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 TriNetX system returned the results of these analyses as csv files which were downloaded and archived. Data presented in this paper and the Appendix can be freely accessed at [URL to be added on publication]. Additionally, TriNetX will grant access to researchers if they have a specific concern (via the third-party agreement option).

BACKGROUND Following administration to persons 60+ years of age, the booster vaccination campaign in Israel was gradually expanded to younger age groups who received a second dose 5 months earlier. We study the booster effect on COVID-19 outcomes. METHODS We extracted data for the period July 30, 2021 to October 6, 2021 from the Israeli Ministry of Health database regarding 4,621,836 persons. We compared confirmed Covid-19 infections, severe illness, and death of those who received a booster ≥12 days earlier (booster group) with a nonbooster group. In a secondary analysis, we compared the rates 3-7 days with ≥12 days after receiving the booster dose. We used Poisson regressions to estimate rate ratios after adjusting for possible confounding factors. RESULTS Confirmed infection rates were ≈10-fold lower in the booster versus nonbooster group (ranging 8.8-17.6 across five age groups) and 4.8-11.2 fold lower in the secondary analysis. Severe illness rates in the primary and secondary analysis were 18.7-fold (95% CI, 15.7-22.4) and 6.5-fold (95% CI, 5.1-8.3) lower for ages 60+, and 22.0-fold (95% CI, 10.3-47.0) and 3.2-fold (95% CI, 1.1-9.6) lower for ages 40-60. For ages 60+, COVID-19 associated death rates were 14.7-fold (95% CI, 9.4-23.1) lower in the primary analysis and 4.8-fold (95% CI, 2.8-8.2) lower in the secondary analysis. CONCLUSIONS Across all age groups, rates of confirmed infection and severe illness were substantially lower among those who received a booster dose of the BNT162b2 vaccine. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement None ### 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 was approved by the institutional review board of the Sheba Medical Center (Helsinki approval number: SMC-8228-21). 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 Aggregated data are given in the supplementary information. Personal data cannot be shared due to privacy.

The microscopic characteristics of the virus that causes Covid disease will determine the macroscopic state in which our world is governed…

Rund 80% der deutschen Bevölkerung leidet heutzutage unter einem Vitamin D Mangel. Gerade wegen solchen Aussagen entscheiden sich immer mehr Menschen dazu, selbständig Vitamin D Präparate zu sich zu nehmen, um einen Mangel auszugleichen oder vorzubeugen. Eine unbedachte Einnahme ohne […]

Zu viel Vitamin D aufzunehmen ist gar nicht so einfach. Erfahren Sie hier, wann es zu einer Vitamin D-Überdosierung kommen kann.

Vitamin D Überdosierung tritt erst bei sehr großen Mengen auf. Allerdings kann hochdosiertes Vitamin D zu Mineralstoffmängeln und Verkalkung führen.

Studies investigating the association between 25-hydroxyvitamin D [25(OH)D] and cognition in the very old (85+) are lacking.Cross-sectional (baseline) and prospective data (up to 3 years follow-up) from 775 participants in the Newcastle 85+ Study ...

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