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The SARS-CoV-2 accessory factor ORF7a downregulates MHC class I surface expression
The SARS-CoV-2 accessory factor ORF7a downregulates MHC class I surface expression
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 500 million infections and more than six million deaths worldwide. Although the viral genomes of SARS-CoV-1 and SARS-CoV-2 share high sequence homology, the clinical and pathological features of COVID-19 differ profoundly from those of SARS. It is apparent that changes in viral genes contribute to the increased transmissibility of SARS-CoV-2 and pathology of COVID-19. Cytotoxic T lymphocytes play a key role in the elimination of virus-infected cells, mediated by recognition of virus-derived peptides that are presented on MHC class I molecules. Here, we show that SARS-CoV-2 can interfere with antigen presentation thereby evading immune surveillance. SARS-CoV-2 infection of monkey and human cell lines resulted in reduced cell-surface expression of MHC class I molecules. We identified a single viral gene product, the accessory factor open reading frame 7a (ORF7a), that mediates this effect. ORF7a interacts with HLA class I molecules in the ER, resulting in ER retention or impaired HLA heavy chain (HC) trafficking to the Golgi. Ultimately, these actions result in reduced HLA class I surface expression on infected cells. Whereas ORF7a from SARS-CoV-2 reduces surface HLA class I levels, the homologous ORF7a from the 2002 pandemic SARS-CoV-1 did not, suggesting that SARS-CoV-2 ORF7a acquired the ability to downregulate HLA-I during evolution of the virus. We identified a single amino acid in the SARS-CoV-1 ORF7a luminal domain that, upon mutating to the corresponding SARS-CoV-2 ORF7a sequence, induced a gain-of-function in HLA surface downregulation. By abrogating HLA class I antigen presentation via ORF7a, SARS-CoV-2 may evade host immune responses by inhibiting anti-viral cytotoxic T cell activity, thereby contributing to the pathology of COVID-19. ### Competing Interest Statement The authors have declared no competing interest.
·biorxiv.org·
The SARS-CoV-2 accessory factor ORF7a downregulates MHC class I surface expression
Early investigation and management of children with acute non-A-E hepatitis, with and without liver failure
Early investigation and management of children with acute non-A-E hepatitis, with and without liver failure
This clinical framework is intended to provide a structure for the investigation, transfer and management of children with novel non-A-E acute hepatitis in the context of an emergence of a novel disease. The recommendations within this guidance are based on existing principles of management of acute hepatitis and acute liver failure and on expert consensus opinion in the absence of high quality evidence around this novel condition.
·rcpch.ac.uk·
Early investigation and management of children with acute non-A-E hepatitis, with and without liver failure
Eric Topol on Twitter
Eric Topol on Twitter
Omicron's lethality rate among seniors was worse than Deltahttps://t.co/DqZooPJKvaThe waning of vaccinations, lack of adequate booster uptake in this high-risk age group were contributory factors— Eric Topol (@EricTopol) May 31, 2022
·twitter.com·
Eric Topol on Twitter
Retracted coronavirus (COVID-19) papers
Retracted coronavirus (COVID-19) papers
via CDC We’ve been tracking retractions of papers about COVID-19 as part of our database. Here’s a running list, which will be updated as needed. (For some context on these figures, see…
·retractionwatch.com·
Retracted coronavirus (COVID-19) papers
Anti-nucleocapsid antibodies following SARS-CoV-2 infection in the blinded phase of the mRNA-1273 Covid-19 vaccine efficacy clinical trial
Anti-nucleocapsid antibodies following SARS-CoV-2 infection in the blinded phase of the mRNA-1273 Covid-19 vaccine efficacy clinical trial
Importance The performance of immunoassays for determining past SARS-CoV-2 infection, which were developed in unvaccinated individuals, has not been assessed in vaccinated individuals. Objective To evaluate anti-nucleocapsid antibody (anti-N Ab) seropositivity in mRNA-1273 vaccine efficacy trial participants after SARS-CoV-2 infection during the trial’s blinded phase. Design Nested analysis in a Phase 3 randomized, placebo-controlled vaccine efficacy trial. Nasopharyngeal swabs for SARS-CoV-2 PCR testing were taken from all participants on Day 1 and Day 29 (vaccination days), and during symptom-prompted illness visits. Serum samples from Days 1, 29, 57, and the Participant Decision Visit (PDV, when participants were informed of treatment assignment, median day 149) were tested for anti-N Abs. Setting Multicenter, randomized, double-blind, placebo-controlled trial at 99 sites in the US. Participants Trial participants were ≥ 18 years old with no known history of SARS-CoV-2 infection and at appreciable risk of SARS-CoV-2 infection and/or high risk of severe Covid-19. Nested sub-study consists of participants with SARS-CoV-2 infection during the blinded phase of the trial. Intervention Two mRNA-1273 (Moderna) or Placebo injections, 28 days apart. Main Outcome and Measure Detection of serum anti-N Abs by the Elecsys (Roche) immunoassay in samples taken at the PDV from participants with SARS-CoV-2 infection during the blinded phase. The hypothesis tested was that mRNA-1273 recipients have different anti-N Ab seroconversion and/or seroreversion profiles after SARS-CoV-2 infection, compared to placebo recipients. The hypothesis was formed during data collection; all main analyses were pre-specified before being conducted. Results We analyzed data from 1,789 participants (1,298 placebo recipients and 491 vaccine recipients) with SARS-CoV-2 infection during the blinded phase (through March 2021). Among participants with PCR-confirmed Covid-19 illness, seroconversion to anti-N Abs at a median follow up of 53 days post diagnosis occurred in 21/52 (40%) of the mRNA-1273 vaccine recipients vs. 605/648 (93%) of the placebo recipients (p 0.001). Higher SARS-CoV-2 viral copies at diagnosis was associated with a higher likelihood of anti-N Ab seropositivity (odds ratio 1.90 per 1-log increase; 95% confidence interval 1.59, 2.28). Conclusions and Relevance As a marker of recent infection, anti-N Abs may have lower sensitivity in mRNA-1273-vaccinated persons who become infected. Vaccination status should be considered when interpreting seroprevalence and seropositivity data based solely on anti-N Ab testing Trial Registration [ClinicalTrials.gov][1] [NCT04470427][2] Question Does prior mRNA-1273 vaccination influence anti-nucleocapsid antibody seroconversion and/or seroreversion after SARS-CoV-2 infection? Findings Among participants in the mRNA-1273 vaccine efficacy trial with PCR-confirmed Covid-19, anti-nucleocapsid antibody seroconversion at the time of study unblinding (median 53 days post diagnosis and 149 days post enrollment) occurred in 40% of the mRNA-1273 vaccine recipients vs. 93% of the placebo recipients, a significant difference. Higher SARS-CoV-2 viral copy number upon diagnosis was associated with a greater chance of anti-nucleocapsid antibody seropositivity (odds ratio 1.90 per 1-log increase; 95% confidence interval 1.59, 2.28). All infections analyzed occurred prior to the circulation of delta and omicron viral variants. Meaning Conclusions about the prevalence and incidence of SARS-CoV-2 infection in vaccinated persons based on anti-nucleocapsid antibody assays need to be weighed in the context of these results. ### Competing Interest Statement All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf. H.E.J. declares support in the form of grants (paid to her institution) from the National Institutes of Health for the submitted work and within the past 36 months, as well as support from a scientific writer/technical editor (independently contracted with her institution) for the submitted work and within the past 36 months. H.Z. is an employee of Moderna Inc. (sponsor of the mRNA-1273-P301 study) and owns Moderna stocks/stock options. B.G. is an employee of Moderna Therapeutics. K.M. declares support from Gilead Sciences, paid to her institution, within the past 36 months for the conduct of phase 3 remdesivir studies for COVID-19 treatment. K.K. declares support in the form of grants (paid to her institution) from the National Institutes of Health within the past 36 months for the conduct of a trial of Novavax's COVID-19 vaccine. L.C. declares support in the form of grants (paid to his institution) from the National Institutes of Health for the submitted work. K.M.N. declares support to her institution (but no salary support) for her role as an investigator on the Phase 1 trial of the Pfizer Covid-19 mRNA vaccine, and also declares salary support from the NIH for her role in co-leading the Coronavirus Prevention Network, which included work on multiple Phase 3 efficacy studies, including the study of the mRNA-1273 vaccine. K.M.N. also serves on a DSMB for a phase-1, open-label, ascending dose evaluation of a live, recombinant Newcastle disease virus expressing the spike protein of SARS-CoV-2 (NDV-HXP-S) sponsored by Icahn School of Medicine at Mount Sinai, is on the Board of Directors for the National Foundation for Infectious Diseases, and is a member of the WHO Strategic Advisory Group of Experts on Immunization (SAGE). J.M.M. is an employee of Moderna and has stock options/grants in Moderna. H.M.E.S. declares support (in the form of grants paid to her institution) from the National Institutes of Health for the submitted work. L.R.B. declares support (in the form of grants paid to his institution) from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) for the conduct of this study as well as grants (paid to his institution) within the last 36 months from NIH/NIAID, Gates Foundation, the Ragon Institute, and Wellcome Trust, outside the submitted work. L.R.B. is involved in HIV, other pathogens, and COVID vaccine clinical trials conducted in collaboration with the NIH, HIV Vaccine Trials Network (HVTN), COVID Vaccine Prevention Network (CoVPN), International AIDS Vaccine Initiative (IAVI), Crucell/Janssen, Moderna, Military HIV Research Program (MHRP), Gates Foundation, and the Ragon Institute. All other authors declare no support from any organization for the submitted work, no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work. ### Funding Statement This study was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases through grants UM1AI068635 (to H.E.J.), UM1AI068614 (to L.C.), 3UM1Al148575-01S2 (to H.M.E.S.), and UM1AI069412 (to L.R.B.). The mRNA-1273-P301 study is sponsored by Moderna, Inc. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. ### 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 mRNA-1273-P301 study is being conducted in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, Good Clinical Practice guidelines, and applicable government regulations. The Central Institutional Review Board approved the mRNA-1273-P301 protocol and the consent forms. All participants provided written informed consent before enrollment. Central IRB services for the mRNA-1273-P301 study were provided by Advarra, Inc., 6100 Merriweather Dr., Suite 600, Columbia, MD 21044. 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 As the trial is ongoing, access to participant-level data and supporting clinical documents with qualified external researchers may be available upon request and is subject to review once the trial is complete. [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04470427&atom=%2Fmedrxiv%2Fearly%2F2022%2F04%2F19%2F2022.04.18.22271936.atom
·medrxiv.org·
Anti-nucleocapsid antibodies following SARS-CoV-2 infection in the blinded phase of the mRNA-1273 Covid-19 vaccine efficacy clinical trial
Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C
Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C
Nature Communications - The antibody response to the SARS-CoV-2 Omicron variant is not well studied in children. Here, the authors provide an age-stratified analysis of SARS-CoV-2 neutralizing...
·nature.com·
Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C
Association between Self-reported Masking Behavior and SARS-CoV-2 Infection Wanes from Pre-Delta to Omicron-Predominant Periods — North Carolina COVID-19 Community Research Partnership
Association between Self-reported Masking Behavior and SARS-CoV-2 Infection Wanes from Pre-Delta to Omicron-Predominant Periods — North Carolina COVID-19 Community Research Partnership
We assessed the association between self-reported mask use during non-household interactions and COVID-19 infection during three pandemic periods. Odds of infection for those who did not always compared to those who always wore a mask was 66% higher during pre-Delta, 53% higher during Delta, declining to 16% higher during Omicron. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement This publication was supported by the Centers for Disease Control and Prevention (CDC) [Contract #75D30120C08405] and the CARES (Coronavirus Aid, Relief, and Economic Security) Act of the U.S. Department of Health and Human Services (HHS) [Contract # NC DHHS GTS #49927]. ### 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: All participants provided informed consent, and Institutional Review Board (IRB) approval was provided by the Wake Forest School of Medicine. 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 Results of the COVID-19 CRP are being disseminated on the study website (https://www.covid19communitystudy.org/) as well as in publications and presentations in medical journals and at scientific meetings. At end of the study, the databases will be made publicly available in a de-identified manner according to CDC and applicable U.S. Federal policies.
·medrxiv.org·
Association between Self-reported Masking Behavior and SARS-CoV-2 Infection Wanes from Pre-Delta to Omicron-Predominant Periods — North Carolina COVID-19 Community Research Partnership
Palaeoserology – teeth put into ancient plagues and pandemics
Palaeoserology – teeth put into ancient plagues and pandemics
Based on archived medical records and evolutionary modelling, a Coronavirus has been hypothesized as root and causative agent of the so-called ‘Russian Flu’ pandemic that surged in 1889–1890. In a Correspondence published in this volume of Microbial Biotechnology, Ramassy and colleagues try to support historical evidence by true experimental data using 'palaeoserology', a novel approach combining archaeology and modern immunological analysis. This Opinion piece tries to weigh arguments how strong such data may be, and where a refinement of methodology might be desirable before textbooks of medical history switch to call the 1890s pandemic ‘Russian Corona’.
·sfamjournals.onlinelibrary.wiley.com·
Palaeoserology – teeth put into ancient plagues and pandemics
Preclinical efficacy, safety, and immunogenicity of PHH-1V, a second-generation COVID-19 vaccine candidate based on a novel recombinant RBD fusion heterodimer of SARS-CoV-2
Preclinical efficacy, safety, and immunogenicity of PHH-1V, a second-generation COVID-19 vaccine candidate based on a novel recombinant RBD fusion heterodimer of SARS-CoV-2
Since the genetic sequence of SARS-CoV-2 became available in January 2020, new vaccines have been developed at an unprecedented speed. The current vaccines have been directly associated with a decline in new infection rates, prevention of severe disease and an outstanding decrease in mortality rates. However, the pandemic is still far from being over. New Variants of Concern (VoCs) are continuously evolving. Thus, it is essential to develop accessible second-generation COVID-19 vaccines against known and future VoCs to mitigate the current pandemic. Here, we provide preclinical data showing the immunogenicity, efficacy, and safety results in mice of a receptor-binding domain (RBD)-based recombinant protein vaccine candidate (PHH-1V) which consists of a novel RBD fusion heterodimer containing the B.1.1.7 (alpha) and B.1.351 (beta) variants of SARS-CoV-2, formulated with an oil-based adjuvant equivalent to MF59C.1. BALB/c and K18-hACE2 mice were immunized with different doses of recombinant RBD fusion heterodimer, following a two-dose prime-and-boost schedule. Upon 20 μg RBD fusion heterodimer/dose immunization, BALB/c mice produced RBD-binding antibodies with neutralising activity against the alpha, beta, gamma, and delta variants. Furthermore, vaccination elicited robust activation of CD4+ and CD8+ T cells with early expression of Th1 cytokines upon in vitro restimulation, along with a good tolerability profile. Importantly, vaccination with 10 μg or 20 μg RBD fusion heterodimer/dose conferred 100% efficacy preventing mortality and bodyweight loss upon SARS-CoV-2 challenge in K18-hACE2 mice. These findings demonstrate the feasibility of this novel recombinant vaccine strategy, allowing the inclusion of up to 2 different RBD proteins in the same vaccine. Most importantly, this new platform is easy to adapt to future VoCs and has a good stability profile, thus ensuring its global distribution. ### Competing Interest Statement Authors indicated as 1 are employees of HIPRA, a private pharmaceutical company that develops and manufactures vaccines. CReSA, IrsiCaixa, CMCiB-IGTP, UPF and ICREA have received financial support from HIPRA.
·biorxiv.org·
Preclinical efficacy, safety, and immunogenicity of PHH-1V, a second-generation COVID-19 vaccine candidate based on a novel recombinant RBD fusion heterodimer of SARS-CoV-2
Jüngste Stiko-Empfehlung: Ein bisschen Impfen?
Jüngste Stiko-Empfehlung: Ein bisschen Impfen?
Diese Woche hat die Stiko die Corona-Impfempfehlung für die Fünf- bis Elfjährigen aktualisiert. Der Neu-Ulmer Hausarzt Dr. Christian Kröner hat sich das Epidemiologisches Bulletin ganz genau angeschaut. In seinem Gastkommentar für den änd schreibt er, was er davon hält.
·aend.de·
Jüngste Stiko-Empfehlung: Ein bisschen Impfen?
The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants
The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants
Vaccination against SARS-CoV-2 protects from infection and improves clinical outcomes in breakthrough infections, likely reflecting residual vaccine-elicited immunity and recall of immunological memory. Here, we defined the early kinetics of spike-specific humoral and cellular immunity after vaccination of seropositive individuals, and after Delta or Omicron breakthrough infection in vaccinated individuals. Early longitudinal sampling revealed the timing and magnitude of recall, with the phenotypic activation of B cells preceding an increase in neutralizing antibody titres. While vaccination of seropositive individuals resulted in robust recall of humoral and T cell immunity, recall of vaccine elicited responses was delayed and variable in magnitude during breakthrough infections, and depended on the infecting variant of concern. While the delayed kinetics of immune recall provides a potential mechanism for the lack of early control of viral replication, the recall of antibodies coincided with viral clearance and likely underpins the protective effects of vaccination against severe COVID-19.
·cell.com·
The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants
Corona OpenData bei Rainer Gerhards - rainer-gerhards.de
Corona OpenData bei Rainer Gerhards - rainer-gerhards.de
Seit Beginn der Pandemie entwickeln wir Lösungen zur Bewertung der Corona-Lage und sammeln hierzu auch viele Daten. Diese Daten wurden bisher hauptsächlich von uns verwendet. In letzter Zeit erreichen uns … „Corona OpenData bei Rainer Gerhards“ weiterlesen
·rainer-gerhards.de·
Corona OpenData bei Rainer Gerhards - rainer-gerhards.de
Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5
Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5
After the global spread of SARS-CoV-2 Omicron BA.2 lineage, some BA.2-related variants that acquire mutations in the L452 residue of spike protein, such as BA.2.9.1 and BA.2.13 (L452M), BA.2.12.1 (L452Q), and BA.2.11, BA.4 and BA.5 (L452R), emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these L452R/M/Q-bearing BA.2-related Omicron variants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1 and BA.2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. Furthermore, infection experiments using hamsters indicated that BA.4/5 is more pathogenic than BA.2. Altogether, our multiscale investigations suggest that the risk of L452R/M/Q-bearing BA.2-related Omicron variants, particularly BA.4 and BA.5, to global health is potentially greater than that of original BA.2. ### Competing Interest Statement Yuki Yamamoto and Tetsuharu Nagamoto are founders and shareholders of HiLung, Inc. Jun Kanamune is an employee of HiLung, Inc. Yuki Yamamoto is a co-inventor of patents (PCT/JP2016/057254; "Method for inducing differentiation of alveolar epithelial cells", PCT/JP2016/059786, "Method of producing airway epithelial cells"). The other authors declare that no competing interests exist.
·biorxiv.org·
Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5
Variant-specific symptoms of COVID-19 among 1,542,510 people in England
Variant-specific symptoms of COVID-19 among 1,542,510 people in England
Infection with SARS-CoV-2 virus is associated with a wide range of symptoms. The REal-time Assessment of Community Transmission -1 (REACT-1) study has been monitoring the spread and clinical manifestation of SARS-CoV-2 among random samples of the population in England from 1 May 2020 to 31 March 2022. We show changing symptom profiles associated with the different variants over that period, with lower reporting of loss of sense of smell and taste for Omicron compared to previous variants, and higher reporting of cold-like and influenza-like symptoms, controlling for vaccination status. Contrary to the perception that recent variants have become successively milder, Omicron BA.2 was associated with reporting more symptoms, with greater disruption to daily activities, than BA.1. With restrictions lifted and routine testing limited in many countries, monitoring the changing symptom profiles associated with SARS-CoV-2 infection and induced changes in daily activities will become increasingly important. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study was funded by the Department of Health and Social Care in England. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of this manuscript. PE is Director of the Medical Research Council (MRC) Centre for Environment and Health (MR/L01341X/1, MR/S019669/1). PE acknowledges support from Health Data Research UK (HDR UK); the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre; NIHR Health Protection Research Units in Chemical and Radiation Threats and Hazards, and Environmental Exposures and Health; the British Heart Foundation Centre for Research Excellence at Imperial College London (RE/18/4/34215); and the UK Dementia Research Institute at Imperial College London (MC\_PC\_17114). HW acknowledges support from an NIHR Senior Investigator Award, the Wellcome Trust (205456/Z/16/Z), and the NIHR Applied Research Collaboration (ARC) North West London. JE is an NIHR academic clinical fellow in infectious diseases. GC is supported by an NIHR Professorship. CAD acknowledges support from the MRC Centre for Global Infectious Disease Analysis, the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections and the NIHR-funded Vaccine Efficacy Evaluation for Priority Emerging Diseases (PR-OD-1017-20007). MC-H and BB acknowledge support from Cancer Research UK, Population Research Committee Project grant 'Mechanomics' (grant No 22184 to MC-H). MC-H acknowledges support from the H2020-EXPANSE (Horizon 2020 grant No 874627) and H2020-LongITools (Horizon 2020 grant No 874739). ### 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: We obtained research ethics approval from the South Central-Berkshire B Research Ethics Committee (IRAS ID: 283787). Notification of favorable opinion and brief summary of the protocol are available here: https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/react1-covid-19-uph/ 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 Access to REACT-1 individual-level data is restricted to protect participants' anonymity. Summary statistics, descriptive tables, and code from the current REACT-1 study are available at https://github.com/mrc-ide/reactidd (doi 10.5281/zenodo.6550327). REACT-1 study materials are available for each round at https://www.imperial.ac.uk/medicine/research-and-impact/groups/react-study/react-1-study-materials/ Sequence read data are available without restriction from the European Nucleotide Archive at https://www.ebi.ac.uk/ena/browser/view/PRJEB37886, and consensus genome sequences are available from the Global initiative on sharing all influenza data (GISAID).
·medrxiv.org·
Variant-specific symptoms of COVID-19 among 1,542,510 people in England
The Effects of Non-pharmaceutical Interventions on COVID-19 Mortality: A Generalized Synthetic Control Approach Across 169 Countries
The Effects of Non-pharmaceutical Interventions on COVID-19 Mortality: A Generalized Synthetic Control Approach Across 169 Countries
ImportanceGovernments have introduced non-pharmaceutical interventions (NPIs) in response to the pandemic outbreak of Coronavirus disease (COVID-19). While NPIs aim at preventing fatalities related to COVID-19, the previous literature on their efficacy has focused on infections and on data of the first half of 2020. Still, findings of early NPI studies may be subject to underreporting and missing timeliness of reporting of cases. Moreover, the low variation in treatment timing during the first wave makes identification of robust treatment effects difficult.ObjectiveWe enhance the literature on the effectiveness of NPIs with respect to the period, the number of countries, and the analytical approach.Design, Setting, and ParticipantsTo circumvent problems of reporting and treatment variation, we analyse data on daily confirmed COVID-19-related deaths per capita from Our World in Data, and on 10 different NPIs from the Oxford COVID-19 Government Response Tracker (OxCGRT) for 169 countries from 1st July 2020 to 1st September 2021. To identify the causal effects of introducing NPIs on COVID-19-related fatalities, we apply the generalized synthetic control (GSC) method to each NPI, while controlling for the remaining NPIs, weather conditions, vaccinations, and NPI-residualized COVID-19 cases. This mitigates the influence of selection into treatment and allows to model flexible post-treatment trajectories.ResultsWe do not find substantial and consistent COVID-19-related fatality-...
·frontiersin.org·
The Effects of Non-pharmaceutical Interventions on COVID-19 Mortality: A Generalized Synthetic Control Approach Across 169 Countries
Post-COVID Condition in Adults and Children Living in the Same Household in Italy: A Prospective Cohort Study Using the ISARIC Global Follow-Up Protocol
Post-COVID Condition in Adults and Children Living in the Same Household in Italy: A Prospective Cohort Study Using the ISARIC Global Follow-Up Protocol
BackgroundEmerging evidence shows that both adults and children may develop post-acute sequelae of SARS-CoV-2 infection (PASC). The aim of this study is to characterise and compare long-term post-SARS-CoV-2 infection outcomes in adults and children in a defined region in Italy.MethodsA prospective cohort study including children (≤18 years old) with PCR-confirmed SARS-CoV-2 infection and their household members. Participants were assessed via telephone and face-to-face visits up to 12 months post-SARS-CoV-2 diagnosis of household index case, using the ISARIC COVID-19 follow-up survey.ResultsOf 507 participants from 201 households, 56.4% (286/507) were children, 43.6% (221/507) adults. SARS-CoV-2 positivity was 87% (249/286) in children, and 78% (172/221) in adults. The mean age of PCR positive children was 10.4 (SD = 4.5) and of PCR positive adults was 44.5 years (SD = 9.5), similar to the PCR negative control groups [children 10.5 years (SD = 3.24), adults 42.3 years (SD = 9.06)]. Median follow-up post-SARS-CoV-2 diagnosis was 77 days (IQR 47–169). A significantly higher proportion of adults compared to children reported at least one persistent symptom (67%, 68/101 vs. 32%, 57/179, p 0.001) at the first follow up. Adults had more frequently coexistence of several symptom categories at both follow-up time-points. Female gender was identified as a risk factor for PASC in adults (p 0.02 at 1–3 months and p 0.01 at 6–9 months follow up), but not in children. We found no sig...
·frontiersin.org·
Post-COVID Condition in Adults and Children Living in the Same Household in Italy: A Prospective Cohort Study Using the ISARIC Global Follow-Up Protocol
Eric Topol on Twitter
Eric Topol on Twitter
It's really striking how well trained scent dogs can detect Covid (and #LongCovid): a randomized controlled, triple-blinded validation trial and real life study at in airport. They need to get retrained for diff't variants https://t.co/gge2ZLMxfk @GlobalHealthBMJ @HelsinkiUniMed pic.twitter.com/9QbE3tzt6Q— Eric Topol (@EricTopol) May 16, 2022
·twitter.com·
Eric Topol on Twitter
Rapid Relapse of Symptomatic Omicron SARS-CoV-2 Infection Following Early Suppression with Nirmatrelvir/Ritonavir
Rapid Relapse of Symptomatic Omicron SARS-CoV-2 Infection Following Early Suppression with Nirmatrelvir/Ritonavir
We describe relapse of COVID-19 symptoms and SARS-CoV-2 viral load following nirmatrelvir/ritonavir (NM/R) in 10 non-immunocompromised patients aged 31 to 71-years-old. Most patients improved rapidly after treatment with NM/R and had negative antigen or PCR tests prior to relapse on Days 9-12 ...
·researchsquare.com·
Rapid Relapse of Symptomatic Omicron SARS-CoV-2 Infection Following Early Suppression with Nirmatrelvir/Ritonavir
SARS-CoV-2 ORF1abA1061S potentiate autoreactive T cell responses via epitope mimicry: an explanation to hepatitis of unknown cause
SARS-CoV-2 ORF1abA1061S potentiate autoreactive T cell responses via epitope mimicry: an explanation to hepatitis of unknown cause
The World Health Organization have recently announced outbreak news of acute, severe hepatitis of unknown cause in children under a Covid-19 pandemic. Whether it is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still under debating. Here, we performed genomic sequence alignment analysis of the genome of SARS-Cov-2 (Wuhan-hu-1) to the human genome reference. Sequence analysis revealed that the SARS-CoV-2 ORF1ab1056-1173 presented high identities with the human protein PAPR1453-176(3Q6Z_A). After searching the fully sequenced SARS-CoV-2 genomes deposited in GISAID (https://www.gisaid.org/), we detected 170 SARS-CoV-2 variants with mutation in ORF1ab1061, where alanine (A) was substituted by serine (S). This alteration made a 7-amino acid peptide (VVVNASN) in ORF1ab1056-1062 identical to its counterpart in PARP1453-59(3Q6Z_A). HLA prediction suggested that the peptides with high identities in PARP14 and ORF1ab could be presented by a same globally prevalent HLA-A*11:01 molecule. And in consistent with the first reported case of hepatitis of unknown, SARS-CoV-2 ORF1abVVVNASN variants were mostly identified as Delta lineages in UK by the late 2021, with an overall frequency of 0.00161%. Thus, our preliminary results raised a possibility that infection by SARS-CoV-2 ORF1abVVVNASN variant might elicit an autoimmune T cell response via epitope mimicry and is associated with the outbreak of unknown hepatitis. We anticipated that these findings will alert the human societies to pay more attention to rare mutations beyond the spike proteins. ### Competing Interest Statement The authors have declared no competing interest.
·biorxiv.org·
SARS-CoV-2 ORF1abA1061S potentiate autoreactive T cell responses via epitope mimicry: an explanation to hepatitis of unknown cause