Covid19-Sources

Background The safety of SARS-CoV-2 vaccines is unknown in children aged

The Omicron lineage of SARS-CoV-2, first described in November 2021, spread rapidly to become globally dominant and has split into a number of sub-lineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africa's Gauteng region uncovered two new sub-lineages, BA.4 and BA.5 which are taking over locally, driving a new wave. BA.4 and BA.5 contain identical spike sequences and, although closely related to BA.2, contain further mutations in the receptor binding domain of spike. Here, we study the neutralization of BA.4/5 using a range of vaccine and naturally immune serum and panels of monoclonal antibodies. BA.4/5 shows reduced neutralization by serum from triple AstraZeneca or Pfizer vaccinated individuals compared to BA.1 and BA.2. Furthermore, using serum from BA.1 vaccine breakthrough infections there are likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections. ### Competing Interest Statement G.R.S. sits on the GSK Vaccines Scientific Advisory Board and is a founder member of RQ Biotechnology. Oxford University holds intellectual property related to the Oxford-Astra Zeneca vaccine and SARS-CoV-2 mAb discovered in G.R.S laboratory. A.J.P. is Chair of UK Dept. Health and Social Care (DHSC) Joint Committee on Vaccination & Immunisation (JCVI) but does not participate in the JCVI COVID-19 committee, and is a member of the WHO SAGE. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, or WHO. The University of Oxford has entered into a partnership with AstraZeneca on coronavirus vaccine development. T.L. is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and was a consultant to Vaccitech for an unrelated project whilst the study was conducted. S.J.D. is a Scientific Advisor to the Scottish Parliament on COVID-19.

This report describes how survivors of COVID-19 were at higher risk for developing many other health conditions.

Background: A substantial proportion of persons who develop COVID-19 report persistent symptoms after acute illness. Various pathophysiologic mechanisms have been implicated in the pathogenesis of postacute sequelae of SARS-CoV-2 infection (PASC). Objective: To characterize medical sequelae and persistent symptoms after recovery from COVID-19 in a cohort of disease survivors and controls. Design: Cohort study. (ClinicalTrials.gov: NCT04411147) Setting: National Institutes of Health Clinical Center, Bethesda, Maryland. Participants: Self-referred adults with laboratory-documented SARS-CoV-2 infection who were at least 6 weeks from symptom onset were enrolled regardless of presence of PASC. A control group comprised persons with no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, recruited regardless of their current health status. Both groups were enrolled over the same period and from the same geographic area. Measurements: All participants had the same evaluations regardless of presence of symptoms, including physical examination, laboratory tests and questionnaires, cognitive function testing, and cardiopulmonary evaluation. A subset also underwent exploratory immunologic and virologic evaluations. Results: 189 persons with laboratory-documented COVID-19 (12% of whom were hospitalized during acute illness) and 120 antibody-negative control participants were enrolled. At enrollment, symptoms consistent with PASC were reported by 55% of the COVID-19 cohort and 13% of control participants. Increased risk for PASC was noted in women and those with a history of anxiety disorder. Participants with findings meeting the definition of PASC reported lower quality of life on standardized testing. Abnormal findings on physical examination and diagnostic testing were uncommon. Neutralizing antibody levels to spike protein were negative in 27% of the unvaccinated COVID-19 cohort and none of the vaccinated COVID-19 cohort. Exploratory studies found no evidence of persistent viral infection, autoimmunity, or abnormal immune activation in participants with PASC. Limitations: Most participants with COVID-19 had mild to moderate acute illness that did not require hospitalization. The prevalence of reported PASC was likely overestimated in this cohort because persons with PASC may have been more motivated to enroll. The study did not capture PASC that resolved before enrollment. Conclusion: A high burden of persistent symptoms was observed in persons after COVID-19. Extensive diagnostic evaluation revealed no specific cause of reported symptoms in most cases. Antibody levels were highly variable after COVID-19. Primary Funding Source: Division of Intramural Research, National Institute of Allergy and Infectious Diseases.

Correspondence from The New England Journal of Medicine — Neutralization Profile after Recovery from SARS-CoV-2 Omicron Infection

Objectives: Establishing the rate of post-vaccination cardiac myocarditis in the 12-15 and 16-17-year-old population in the context of their COVID-19 hospitalization risk is critical for developing a vaccination recommendation framework that balances harms with benefits for this patient demographic. Design, Setting and Participants: Using the Vaccine Adverse Event Reporting System (VAERS), this retrospective epidemiological assessment reviewed reports filed between January 1, 2021, and June 18, 2021, among adolescents ages 12-17 who received mRNA vaccination against COVID-19. Symptom search criteria included the words myocarditis, pericarditis, and myopericarditis to identify children with evidence of cardiac injury. The word troponin was a required element in the laboratory findings. Inclusion criteria were aligned with the CDC working case definition for probable myocarditis. Stratified cardiac adverse event (CAE) rates were reported for age, sex and vaccination dose number. A harm-benefit analysis was conducted using existing literature on COVID-19-related hospitalization risks in this demographic. Main outcome measures: 1) Stratified rates of mRNA vaccine-related myocarditis in adolescents age 12-15 and 16-17; and 2) harm-benefit analysis of vaccine-related CAEs in relation to COVID-19 hospitalization risk. Results: A total of 257 CAEs were identified. Rates per million following dose 2 among males were 162.2 (ages 12-15) and 94.0 (ages 16-17); among females, rates were 13.0 and 13.4 per million, respectively. For boys 12-15 without medical comorbidities receiving their second mRNA vaccination dose, the rate of CAE is 3.7-6.1 times higher than their 120-day COVID-19 hospitalization risk as of August 21, 2021 (7-day hospitalizations 1.5/100k population) and 2.6-4.3-fold higher at times of high weekly hospitalization risk (2.1/100k), such as during January 2021. For boys 16-17 without medical comorbidities, the rate of CAE is currently 2.1-3.5 times higher than their 120-day COVID-19 hospitalization risk, and 1.5-2.5 times higher at times of high weekly COVID-19 hospitalization. Conclusions: Post-vaccination CAE rate was highest in young boys aged 12-15 following dose two. For boys 12-17 without medical comorbidities, the likelihood of post vaccination dose two CAE is 162.2 and 94.0/million respectively. This incidence exceeds their expected 120-day COVID-19 hospitalization rate at both moderate (August 21, 2021 rates) and high COVID-19 hospitalization incidence. Further research into the severity and long-term sequelae of post-vaccination CAE is warranted. Quantification of the benefits of the second vaccination dose and vaccination in addition to natural immunity in this demographic may be indicated to minimize harm. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement There was no funding received for this study. ### 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: NA 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 used in this analysis are available at the link listed below.

Summary Background Vaccination against COVID-19 is the cornerstone to control and mitigate the ongoing pandemic. Thrombotic adverse events linked to Moderna, Pfizer and the Oxford-AstraZeneca vaccine have been documented and described as extremely rare. While the Oxford-AstraZeneca vaccine has received much of the attention, the other vaccines should not go unchallenged. This study aimed to determine the frequency of reported thrombotic adverse events and clinical outcomes for these three COVID-19 vaccines, namely, Moderna, Pfizer and Oxford-AstraZeneca Methods A retrospective descriptive analysis was conducted of spontaneous reports for Moderna, Pfizer and Oxford-AstraZeneca COVID-19 vaccines submitted to the EudraVigilance database in the period from 17 February to 14 June 2021. Findings There were 729,496 adverse events for the three vaccines, of which 3,420 were thrombotic, mainly Oxford-AstraZeneca (n=1,988; 58.1%) followed by Pfizer (n=1,096; 32.0%) and Moderna (n=336; 9.8%). As serious adverse events, there were 705 reports of pulmonary embolism for the three vaccines, of which 130 reports (18.4%) were for Moderna, 226 reports (32.1%) for Pfizer and 349 (49.5%) for Oxford-AstraZeneca vaccines. The occurrence of pulmonary embolism is significantly associated with a fatal outcome (P=

Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the...

Correspondence from The New England Journal of Medicine — SARS-CoV-2 Neutralization with BNT162b2 Vaccine Dose 3

Bei insgesamt 36 291 Todesbescheinigungen war im Jahr 2020 laut vorläufigen Daten der Todesursachenstatistik COVID-19 als Erkrankung vermerkt. In 30 136 Fällen war dies die Todesursache, in den anderen 6 155 Fällen war es eine Begleiterkrankung. Nach diesen ersten vorläufigen Angaben des Statistischen Bundesamtes (Destatis) starben somit in 83 % dieser Fälle die betroffenen Personen an COVID-19 als sogenanntem Grundleiden, das heißt die Krankheit war die für den Tod verantwortliche Todesursache. In 17 % der Fälle starben die Personen mit COVID-19 als Begleiterkrankung, jedoch an einem anderen Grundleiden. Dies geht aus den vorläufigen Ergebnissen der Todesursachenstatistik hervor, die ab dem Berichtszeitraum Januar 2020 erstmals monatlich veröffentlicht werden und die bis zur vorliegenden Auswertung knapp 92 % aller Sterbefälle umfassen.

New @TheLancetInfDis Reduction in vaccine + booster effectiveness vs hospitalization for BA.2 vs BA.1 variants at 10+ weeks https://t.co/PZ6r29aba510-14 wks: 70.2 vs 85.415+ wks: 56.5 vs 80.4See table below for 95% CI and text for detailsby @freja_kirsebom and colleagues pic.twitter.com/VLEmW0t2js— Eric Topol (@EricTopol) May 24, 2022

Human coronaviruses (HCoV) cause common colds but can also infect neural cell cultures. To provide definitive experimental evidence for the neurotropism and neuroinvasion of HCoV and its possible association with multiple sclerosis (MS), we have performed ...

Marit J. van Gils and colleagues investigate antibody responses against diverse emerging SARS-CoV-2 variants induced by four different SARS-CoV-2 vaccines in health care workers in the Netherlands.

Recent studies suggest that medication that stabilizes mast cell activation may help both conditions.

Out now – our preprint "A live attenuated vaccine confers superior mucosal and systemic immunity to SARS-CoV-2 variants", comparing live attenuated/mRNA/Adeno vaccines using histopathology, serology, scRNA-seq in hamsters.https://t.co/V1rquNNbXF – summary in the thread … (1/8) pic.twitter.com/UNnR5ZMK8k— Emanuel Wyler (@ewyler) May 17, 2022

Vaccines are a cornerstone in COVID-19 pandemic management. Here, we compare immune responses to and preclinical efficacy of the mRNA vaccine BNT162b2, an adenovirus-vectored spike vaccine, and the live-attenuated-virus vaccine candidate sCPD9 after single and double vaccination in Syrian hamsters. All regimens containing sCPD9 showed superior efficacy. The robust immunity elicited by sCPD9 was evident in a wide range of immune parameters after challenge with heterologous SARS-CoV-2 including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue. Our results demonstrate that use of live-attenuated vaccines may offer advantages over available COVID-19 vaccines, specifically when applied as booster, and may provide a solution for containment of the COVID-19 pandemic. ### Competing Interest Statement Related to this work, Freie Universität Berlin has filed a patent application for the use of sCPD9 as vaccine in humans. In this application, JT, NO and DK are named as inventors of sCPD9. Freie Universität Berlin is collaborating with RocketVax Inc. for further development of sCPD9 and receives funding for research. Independent of this work GN has received project funding from Biotest AG. Independent of this work MW received funding for research from Bayer Health Care, Biotest, Pantherna, Vaxxilon, and for lectures and advisory from Alexion, Aptarion, Astra Zeneca, Bayer Health Care, Berlin Chemie, Biotest, Boehringer Ingelheim, Chiesi, Glaxo Smith Kline, Insmed, Novartis, Teva and Vaxxilon. The other authors declare that they have no competing interest.

Novel intranasal COVID-19 vaccine, CoviLivTM, induced strong cellular immune response in healthy adults against many conserved proteins in known variants of SARS-CoV-2, in particular, a peptide pool 99% Omicron BA.2. Spike protein focused vaccines have shown lower protection against viral mutants.1 Unlike other spike-only vaccine approaches that may need to re-formulate as COVID evolves, this…

SARS-CoV-2 infection is associated with a surprising number of morbidities. Uncanny similarities with amyloid-disease associated blood coagulation and fibrinolytic disturbances together with neurologic and cardiac problems led us to investigate the amyloidogenicity of the SARS-CoV-2 spike protein (S-protein). Amyloid fibril assays of peptide library mixtures and theoretical predictions identified seven amyloidogenic sequences within the S-protein. All seven peptides in isolation formed aggregates during incubation at 37 °C. Three 20-amino acid long synthetic spike peptides (sequence 192–211, 601–620, 1166–1185) fulfilled three amyloid fibril criteria: nucleation dependent polymerization kinetics by ThT, Congo red positivity, and ultrastructural fibrillar morphology. Full-length folded S-protein did not form amyloid fibrils, but amyloid-like fibrils with evident branching were formed during 24 h of S-protein coincubation with the protease neutrophil elastase (NE) in vitro. NE efficiently cleaved S-protein, rendering exposure of amyloidogenic segments and accumulation of the amyloidogenic peptide 194–203, part of the most amyloidogenic synthetic spike peptide. NE is overexpressed at inflamed sites of viral infection. Our data propose a molecular mechanism for potential amyloidogenesis of SARS-CoV-2 S-protein in humans facilitated by endoproteolysis. The prospective of S-protein amyloidogenesis in COVID-19 disease associated pathogenesis can be important in understanding the disease and long COVID-19.

The rising case numbers of the SARS-CoV-2 Omicron BA.4, BA.5, and BA.2.12.1 subvariants has generated serious concern about the course of the pandemic. Here we examine the neutralization resistance, infectivity, processing, and fusogenicity of spike from the BA.4/5 and BA.2.12.1 SARS-CoV-2 variants compared with other Omicron subvariants and Delta. Critically, we found that the new Omicron subvariants BA.4/5 and BA.2.12.1 were more resistant to neutralization by mRNA-vaccinated and boosted health care worker sera and Omicron-BA.1-wave patient sera than were the BA.1 and BA.2 variants. Interestingly, Delta-wave patient sera neutralized more efficiently against not only Delta but also BA.4/5 and BA.2.12.1 variants that also contain substitutions at position L452, similar to Delta. The BA.4/5 and BA.2.12.1 variants also exhibited higher fusogenicity, and increased spike processing, dependent on the L452 substitution. These results highlight the key role of the L452R and L452Q mutations in BA.4/5 and BA.2.12.1 subvariants. ### Competing Interest Statement The authors have declared no competing interest.

Derzeit haben in Deutschland erst 5,8% der Bevölkerung eine vierte Impfung erhalten, und auch bei den über 60-jährigen sind es gerade mal 17,5%.Vor diesem Hintergrund hier ein Thread mit einem Überblick…#ImpfenSchuetzt#COVID19#LongCovid#coronavirushttps://t.co/epYiNhiYIt pic.twitter.com/dUROI7Wdd3— Ralf Wittenbrink (@RWittenbrink) May 21, 2022

We conducted a distributed network cohort study using primary care records from the Netherlands, Italy, Spain, and the UK, and outpatient specialist records from Germany. The Spanish database was linked to hospital admissions. Participants were followed up from the date of a diagnosis of COVID-19 or positive RT-PCR test for SARS-CoV-2 (index date) for 90 days. The primary study outcomes were venous thromboembolic events, arterial thromboembolic events, and death, all over the 90 days from the index date. We estimated cumulative incidences for the study outcomes. Multistate models were used to calculate adjusted hazard ratios (HRs) for the association between venous thromboembolism or arterial thromboembolism occurrence and risks of hospitalisation or COVID-19 fatality. Findings Overall, 909 473 COVID-19 cases and 32 329 patients hospitalised with COVID-19 on or after Sept 1, 2020, were studied. The latest index dates across the databases ranged from Jan 30, 2021, to July 31, 2021. Cumulative 90-day incidence of venous thromboembolism ranged from 0·2% to 0·8% among COVID-19 cases, and up to 4·5% for those hospitalised. For arterial thromboembolism, estimates ranged from 0·1% to 0·8% among COVID-19 cases, increasing to 3·1% among those hospitalised. Case fatality ranged from 1·1% to 2·0% among patients with COVID-19, rising to 14·6% for hospitalised patients. The occurrence of venous thromboembolism in patients with COVID-19 was associated with an increased risk of death (adjusted HRs 4·42 [3·07–6·36] for those not hospitalised and 1·63 [1·39–1·90] for those hospitalised), as was the occurrence of arterial thromboembolism (3·16 [2·65–3·75] and 1·93 [1·57–2·37]). Interpretation Risks of venous thromboembolism and arterial thromboembolism were up to 1% among COVID-19 cases, and increased with age, among males, and in those who were hospitalised. Their occurrence was associated with excess mortality, underlying the importance of developing effective treatment strategies that reduce their frequency.

It's not a problem entirely solved by highly vaccinated population or Omicron though - over 400,000 people developed Long Covid from Omicron (and that's not including the big March wave!). 5/8 pic.twitter.com/EwKkKwXXxe— Prof. Christina Pagel 🇺🇦 (@chrischirp) May 17, 2022

Background. A growing number of long COVID cases after infection have been reported. By definition, long COVID is the condition whereby affected individ

Omicron s escape to vaccine-induced systemic antibody responses has been shown in several studies in Omicron-infected patients and vaccine controls. In the present study we compared mucosal antibody response to Omicron to mucosal antibody response to ancestral strain and Delta variant. This was done on nasal epithelial lining fluid (NELF) prospectively collected in 84 otherwise healthy healthcare workers who had never exhibited PCR-documented COVID-19 and had received three doses of the Pfizer-BioNTech COVID-19 mRNA vaccine. NELF was collected prior to Omicron detection in the geographical area of inclusion. We show that NELF antibodies from vaccinated individuals were less efficient at inhibiting the binding of the Omicron Spike protein to ACE-2 compared to those of Delta or the ancestral strain. These findings may explain the increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta in countries with a high vaccination coverage. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Research reported in this publication was supported by grants from the Conseil Departemental des Alpes Maritimes, the Metropole Nice Cote dAzur. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the CPP Sud Mediterranee V ethics committee 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

The World Health Organisation (WHO) has been tracking the impact of COVID-19 as the pandemic has evolved over time. Aggregate case and death numbers are being reported to the WHO and the data have been made publicly available at https://covid19.who.int/. For a number of reasons, these data do not provide a complete picture of the health burden attributable to COVID-19, nor of how many lives have been lost due to the pandemic. Some deaths that are attributable to COVID-19 have not been certified as such because tests had not been conducted prior to death. There have also been variations in the death certification rules countries have applied in regards to COVID-19 (Riffe and Acosta, 2021). The impact of the pandemic is far reaching. Beyond the deaths directly attributable to it are those that can be linked to the conditions that have prevailed since the pandemic began and have led to some health systems being overwhelmed or some patients avoiding healthcare. In countries where COVID-19 spread was limited, due to lockdown measures or otherwise, some potential causes of death have decreased, such as those attributable to air pollution, or traffic accidents, or from other communicable diseases such as influenza like illness, resulting in negative excess or deficit deaths (Kung, Doppen, Black, Hills, and Kearns, 2020; Karlinsky and Kobak, 2021).

Risk Factors for SARS-CoV-2 in Cats and Dogs

Berlin – In Deutschland haben sich nach Schätzungen der Bundesregierung schon 50 Millionen Menschen mit dem Coronavirus SARS-CoV-2 infiziert. Bundesweit sind... #Coronainfektionen #Deutschland

Early anecdotes about Paxlovid’s effects on long COVID are intriguing, but no one’s testing them in clinical trials yet.

There is ample evidence that masking and social distancing are effective in reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. However, due to the complexity of airborne disease transmission, it is difficult to quantify their effectiveness, especially in the case of one-to-one exposure. Here, we introduce the concept of an upper bound for one-to-one exposure to infectious human respiratory particles and apply it to SARS-CoV-2. To calculate exposure and infection risk, we use a comprehensive database on respiratory particle size distribution; exhalation flow physics; leakage from face masks of various types and fits measured on human subjects; consideration of ambient particle shrinkage due to evaporation; and rehydration, inhalability, and deposition in the susceptible airways. We find, for a typical SARS-CoV-2 viral load and infectious dose, that social distancing alone, even at 3.0 m between two speaking individuals, leads to an upper bound of 90% for risk of infection after a few minutes. If only the susceptible wears a face mask with infectious speaking at a distance of 1.5 m, the upper bound drops very significantly; that is, with a surgical mask, the upper bound reaches 90% after 30 min, and, with an FFP2 mask, it remains at about 20% even after 1 h. When both wear a surgical mask, while the infectious is speaking, the very conservative upper bound remains below 30% after 1 h, but, when both wear a well-fitting FFP2 mask, it is 0.4%. We conclude that wearing appropriate masks in the community provides excellent protection for others and oneself, and makes social distancing less important.