Corpus overview


Overview

MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (2227)

ProteinN (575)

NSP5 (418)

ComplexRdRp (253)

ProteinE (148)


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SARS-CoV-2 Proteins
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    Clinical coding of long COVID in English primary care: a federated analysis of 58 million patient records in situ using OpenSAFELY

    Authors: - The OpenSAFELY Collaborative; Alex J Walker; Brian MacKenna; Peter Inglesby; Christopher T Rentsch; Helen J Curtis; Caroline E Morton; Jessica Morley; Amir Mehrkar; Sebastian CJ Bacon; George Hickman; Christopher Bates; Richard Croker; David Evans; Tom Ward; Jonathan Cockburn; Simon Davy; Krishnan Bhaskaran; Anna Schultze; Elizabeth J Williamson; William J Hulme; Helen I McDonald; Laurie Tomlinson; Rohini Mathur; Rosalind M Eggo; Kevin Wing; Angel YS Wong; Harriet Forbes; John Tazare; John Parry; Frank Hester; Sam Harper; Shaun O'Hanlon; Alex Eavis; Richard Jarvis; Dima Avramov; Paul Griffiths; Aaron Fowles; Nasreen Parkes; Ian J Douglas; Stephen JW Evans; Liam Smeeth; Ben Goldacre

    doi:10.1101/2021.05.06.21256755 Date: 2021-05-13 Source: medRxiv

    Background Long COVID is a term to describe new or persistent symptoms at least four weeks after onset of acute COVID-19 MESHD. Clinical codes to describe this phenomenon were released in November 2020 in the UK, but it is not known how these codes have been used in practice. Methods Working on behalf of NHS England, we used OpenSAFELY data encompassing 96% of the English population. We measured the proportion of people with a recorded code for long COVID, overall and by demographic factors, electronic health record software system, and week. We also measured variation in recording amongst practices. Results Long COVID was recorded for 23,273 people. Coding was unevenly distributed amongst practices, with 26.7% of practices having not used the codes at all. Regional variation was high, ranging between 20.3 per 100,000 people for East of England (95% confidence interval 19.3-21.4) and 55.6 in London (95% CI 54.1-57.1). The rate was higher amongst women (52.1, 95% CI 51.3-52.9) compared to men (28.1, 95% CI 27.5-28.7), and higher amongst practices using EMIS software (53.7, 95% CI 52.9-54.4) compared to TPP software (20.9, 95% CI 20.3-21.4). Conclusions Long COVID coding in primary care is low compared with early reports of long COVID prevalence. This may reflect under-coding, sub-optimal communication of clinical terms, under-diagnosis, a true low prevalence of long COVID diagnosed by clinicians, or a combination of factors. We recommend increased awareness of diagnostic codes, to facilitate research and planning of services; and surveys of clinicians' experiences, to complement ongoing patient surveys.

    SARS-CoV-2 RNA and antibody detection in human milk from a prospective multicenter study in Spain

    Authors: Christine Bauerl; Walter Randazzo; Gloria Sanchez; Marta Selma-Royo; Elia Garcia-Verdevio; Laura Martinez-Rodriguez; Anna Parra-Llorca; Carles Lerin; Victoria Fumado; Francesca Crovetto; Fatima Crispi; Francisco Jose Perez-Cano; Gerardo Rodriguez; Gema Ruiz-Redondo; Cristina Campoy; Cecilia Martinez-Costa; Maria Carmen Collado

    doi:10.1101/2021.05.06.21256766 Date: 2021-05-13 Source: medRxiv

    Background: During the COVID-19 pandemic MESHD in 2020, breastfeeding in women positive for SARS-CoV-2 was compromised due to contradictory data regarding potential viral transmission. However, growing evidence confirms the relevant role of breast milk MESHD in providing passive immunity by generating and transmitting specific antibodies against the virus. Thus, our study aimed to develop and validate a specific protocol to detect SARS-CoV-2 in breast milk matrix as well as to determine the impact of maternal SARS-CoV-2 infection MESHD on presence, concentration, and persistence of specific SARS-CoV-2 antibodies. Study design/Methods: A prospective multicenter longitudinal study in Spain was carried out from April to December 2020. A total of 60 mothers with SARS-CoV-2 infection MESHD and/or recovered from COVID-19 MESHD were included (n=52 PCR-diagnosed and n=8 seropositive). Data from maternal-infant clinical records and symptomatology were collected. A specific protocol was validated to detect SARS-CoV-2 RNA in breast milk MESHD, targeting the N1 region of the nucleocapsid gene and the envelope ( E) gene PROTEIN. Presence and levels of SARS-CoV-2 specific immunoglobulins (Igs) - IgA HGNC, IgG, and IgM- in breast milk samples from COVID-19 MESHD patients and from 13 women before the pandemic were also evaluated. Results: All breast milk MESHD samples showed negative results for SARS-CoV-2 RNA presence. We observed high intra- and inter-individual variability in the antibody response to the receptor-binding domain (RBD) of the SARS-CoV-2 spike PROTEIN protein for each of the three isotypes IgA HGNC, IgM and IgG. Protease domain (MPro) antibodies were also detected in milk. In general, 82.9 % of the milk samples were positive for at least one of the three antibody isotypes, being 52.86 % of those positive for all three Igs. Positivity rate for IgA HGNC was relatively stable over time (65.2-87.5 %), whereas it raised continuously for IgG (47.8 % the first ten days to 87.5 % from day 41 up to day 206 post-PCR confirmation). Conclusions: Considering the lack of evidence for SARS-CoV-2 transmission through breast milk MESHD, our study confirms the safety of breastfeeding practices and highlights the relevance of virus-specific SARS-CoV-2 antibody transfer, that would provide passive immunity to breastfed infants and protect them against COVID-19 MESHD disease. This study provides crucial data to support official breastfeeding recommendations based on scientific evidence.

    COVID-19 MESHD wastewater based epidemiology: long-term monitoring of 10 WWTP in France reveals the importance of the sampling context

    Authors: Adele LAZUKA; Charlotte Arnal; Emmanuel Soyeux; Mickael Sampson; Anne-Sophie Lepeuple; Yannick Deleuze; Stanislas Pouradier Duteil; Sebastien Lacroix

    doi:10.1101/2021.05.06.21256751 Date: 2021-05-13 Source: medRxiv

    SARS-CoV-2 wastewater-based epidemiology (WBE) has been advanced as a relevant indicator of distribution of COVID-19 MESHD in communities, supporting classical testing and tracing epidemiological approaches. An extensive sampling campaign, including ten municipal wastewater treatment plants, has been conducted in different cities of France over a 20-weeks period, encompassing the second peak of COVID-19 MESHD outbreak in France. A well-recognised ultrafiltration - RNA extraction - RT-qPCR protocol was used and qualified, showing 5.5 +/- 0.5% recovery yield on heat-inactivated SARS-CoV-2. Importantly the whole, solid and liquid, fraction of wastewater was used for virus concentration in this study. Campaign results showed medium- to strong- correlation between SARS-CoV-2 WBE data and COVID-19 MESHD prevalence. To go further, WWTP inlet flow rate and raining statistical relationships were studied and taken into account for each WWTP in order to calculate contextualized SARS-CoV-2 loads. This metric presented improved correlation strengths with COVID-19 MESHD prevalence for WWTP particularly submitted and sensitive to rain. Such findings highlighted that SARS-CoV-2 WBE data ultimately require to be contextualised for relevant interpretation.

    Pharmacogenomic and drug interaction risk associations with hospital length of stay among Medicare Advantage members with COVID-19 MESHD

    Authors: Kristine Ashcraft; Chad Moretz; Chantelle Schenning; Susan Rojahn; Kae Vines Tanudtanud; Gwyn Omar Magoncia; Justine Reyes; Bernardo Marquez; Yinglong Guo; Elif Tokar-Erdemir; Taryn O. Hall

    doi:10.1101/2021.05.06.21256769 Date: 2021-05-13 Source: medRxiv

    Importance: COVID-19 MESHD has severely impacted older populations and strained healthcare resources, with many patients requiring long periods of hospitalization. Reducing the hospital length of stay (LOS) reduces patient and hospital burden. Given that adverse drug reactions are known to prolong LOS, unmanaged pharmacogenomic risk and drug interactions among COVID-19 MESHD patients may be a risk factor for longer hospital stays. Objective: The objective of this study was to determine if pharmacogenomic and drug interaction risks were associated with longer lengths of stay among high-risk patients hospitalized with COVID-19 MESHD. Design: Retrospective cohort study of medical and pharmacy claims Setting: Administrative database from a large U.S. health insurance company Participants: Medicare Advantage members with a first COVID-19 MESHD hospitalization between January 2020 and June 2020, who did not die during the stay. Exposures: (1) Pharmacogenetic interaction probability ( PIP HGNC) of [≤]25% (low), 26%-50% (moderate), or >50% (high), which indicate the likelihood that one or more clinically actionable gene-drug or gene-drug-drug interactions would be identified with testing; (2) drug-drug interaction (DDI) severity of minimal, minor, moderate, major, or contraindicated, which indicate the severity of an interaction between two or more active medications. Main Outcomes and Measures: The primary outcome was hospital length of stay. Results were stratified by hierarchical condition categories (HCC) counts and chronic conditions. Results: A total of 6,025 patients hospitalized with COVID-19 MESHD were included in the study. Patients with moderate or high PIP HGNC were hospitalized for 9% (CI: 4%-15%; p < 0.001) and 16% longer (CI: 8%-24%; p < 0.001), respectively, compared to those with low PIP HGNC, whereas RAF HGNC score was not associated with LOS. High PIP HGNC was significantly associated with 12%-22% longer lengths of stay compared to low PIP HGNC in patients with hypertension MESHD, hyperlipidemia MESHD, diabetes MESHD, or COPD MESHD. Finally, among patients with 2 or 3 HCCs, a 10% longer length of stay was observed among patients with moderate or more severe DDI compared to minimal or minor DDI. Conclusions and Relevance: Proactively mitigating pharmacogenomic risk has the potential to reduce length of stay in patients hospitalized with COVID-19 MESHD especially those with COPD MESHD, diabetes MESHD, hyperlipidemia MESHD, and hypertension MESHD.

    Optimizing the spatio-temporal allocation of COVID-19 MESHD vaccines: Italy as a case study

    Authors: Joseph Chadi Lemaitre; Damiano Pasetto; Mario Zanon; Enrico Bertuzzo; Lorenzo Mari; Stefano Miccoli; Renato Casagrandi; Marino Gatto; Andrea Rinaldo

    doi:10.1101/2021.05.06.21256732 Date: 2021-05-13 Source: medRxiv

    While SARS-CoV-2 vaccine distribution campaigns are underway across the world, communities face the challenge of a fair and effective distribution of limited supplies. We wonder whether suitable spatial allocation strategies might significantly improve a campaign's efficacy in averting damaging outcomes. To that end, we address the problem of optimal control of COVID-19 MESHD vaccinations in a country-wide geographic and epidemiological context characterized by strong spatial heterogeneities in transmission rate and disease history. We seek the vaccine allocation strategies in space and time that minimize the number of infections in a prescribed time horizon. We examine scenarios of unfolding disease transmission across the 107 provinces of Italy, from January to April 2021, generated by a spatially explicit compartmental COVID-19 MESHD model tailored to the Italian geographic and epidemiological context. We develop a novel optimal control framework to derive optimal vaccination strategies given the epidemiological projections and constraints on vaccine supply and distribution logistic. Optimal schemes significantly outperform simple alternative allocation strategies based on incidence, population distribution, or prevalence of susceptibles in each province. Our results suggest that the complex interplay between the mobility network and the spatial heterogeneities imply highly non-trivial prioritization of local vaccination campaigns. The extent of the overall improvements in the objectives grants further inquiry aimed at refining other possibly relevant factors so far neglected. Our work thus provides a proof-of-concept of the potential of optimal control for complex and heterogeneous epidemiological contexts at country, and possibly global, scales.

    CV2CoV, an enhanced mRNA-based SARS-CoV-2 vaccine candidate, supports higher protein expression and improved immunogenicity in rats

    Authors: Nicole Roth; Jacob Schoen; Donata Hoffmann; Moritz Thran; Andreas Thess; Stefan O. Mueller; Benjamin Petsch; Susanne Rauch

    doi:10.1101/2021.05.13.443734 Date: 2021-05-13 Source: bioRxiv

    More than a year after emergence of the SARS-CoV-2 pandemic, multiple first-generation vaccines are approved and available for vaccination. Still, many challenges remain. The ongoing vaccination programs across the globe suffer from insufficient vaccine supply. The virus is adapting to the human host and novel variants are circulating that are neutralised less efficiently by antibodies raised against ancestral SARS-CoV-2 variants. Here, we describe CV2CoV, a second-generation mRNA vaccine developed for enhanced protein expression and immunogenicity. CV2CoV supports increased levels of protein expression in cell culture compared to our clinical candidate CVnCoV. Vaccination with CV2CoV induces high levels of virus neutralising antibodies with accelerated kinetics in rats. Robust antibody responses are reflected in significant cross-neutralisation of circulating SARS-CoV-2 variants of concern, i.e. B.1.1.7 and B.1.351. Together, these results underline the value of CV2CoV as next-generation SARS-CoV-2 mRNA vaccine

    Plasmacytoid dendritic cells produce type I interferon and reduce viral replication in airway epithelial cells after SARS-CoV-2 infection MESHD

    Authors: Luisa Cervantes-Barragan; Abigail Vanderheiden; Charlotte J Royer; Meredith E Davis-Gardner; Philipp Ralfs; Tatiana Chirkova; Larry J Anderson; Arash Grakoui; Mehul S Suthar

    doi:10.1101/2021.05.12.443948 Date: 2021-05-13 Source: bioRxiv

    Infection with SARS-CoV-2 has caused a pandemic of unprecedented dimensions. SARS-CoV-2 infects MESHD airway and lung cells causing viral pneumonia MESHD. The importance of type I interferon (IFN) HGNC production for the control of SARS-CoV-2 infection MESHD is highlighted by the increased severity of COVID-19 MESHD in patients with inborn errors of type I IFN MESHD response or auto-antibodies against IFN HGNC-. Plasmacytoid dendritic cells (pDCs) are a unique immune cell population specialized in recognizing and controlling viral infections through the production of high concentrations of type I IFN. In this study, we isolated pDCs from healthy donors and showed that pDCs are able to recognize SARS-CoV-2 and rapidly produce large amounts of type I IFN. Sensing of SARS-CoV-2 by pDCs was independent of viral replication since pDCs were also able to recognize UV-inactivated SARS-CoV-2 and produce type I IFN. Transcriptional profiling of SARS-CoV-2 and UV-SARS-CoV-2 stimulated pDCs also showed a rapid type I and III IFN response as well as induction of several chemokines, and the induction of apoptosis in pDCs. Moreover, we modeled SARS-CoV-2 infection MESHD in the lung using primary human airway epithelial cells (pHAEs) and showed that co-culture of pDCs with SARS-CoV-2 infected pHAEs MESHD induces an antiviral response and upregulation of antigen presentation in pHAE cells. Importantly, the presence of pDCs in the co-culture results in control of SARS-CoV-2 replication in pHAEs. Our study identifies pDCs as one of the key cells that can recognize SARS-CoV-2 infection MESHD, produce type I and III IFN and control viral replication in infected cells.

    Impact of vaccination on the COVID-19 pandemic MESHD: Evidence from U.S. states

    Authors: Xiao Chen; Hanwei Huang; Jiandong Ju; Ruoyan Sun; Jialiang Zhang

    doi:10.1101/2021.05.08.21256892 Date: 2021-05-12 Source: medRxiv

    Governments worldwide are implementing mass vaccination programs in an effort to end the novel coronavirus ( COVID-19 MESHD) pandemic. Although the approved vaccines exhibited high efficacies in randomized controlled trials, their population effectiveness in the real world remains less clear, thus casting uncertainty over the prospects for herd immunity. In this study, we evaluated the effectiveness of the COVID-19 MESHD vaccination program and predicted the path to herd immunity in the U.S. Using data from 12 October 2020 to 7 March 2021, we estimated that vaccination reduced the total number of new cases by 4.4 million (from 33.0 to 28.6 million), prevented approximately 0.12 million hospitalizations (from 0.89 to 0.78 million), and decreased the population infection rate by 1.34 percentage points (from 10.10% to 8.76%). We then built a Susceptible-Infected-Recovered (SIR) model with vaccination to predict herd immunity. Our model predicts that if the average vaccination pace between January and early March 2021 (2.08 doses per 100 people per week) is maintained, the U.S. can achieve herd immunity by the last week of July 2021, with a cumulative vaccination coverage of 60.2%. Herd immunity could be achieved earlier with a faster vaccination pace, lower vaccine hesitancy, or higher vaccine effectiveness. These findings improve our understanding of the impact of COVID-19 MESHD vaccines and can inform future public health policies regarding vaccination, especially in countries with ongoing vaccination programs.

    Comprehensive and Temporal Surveillance of SARS-CoV-2 in Urban Water Bodies: Early Signal of Second Wave Onset

    Authors: Manupati Hemalatha; Athmakuri Tharak; Harishankar Kopperi; Uday Kiran; C.G. Gokulan; Rakesh K Mishra; S Venkata Mohan Sr.

    doi:10.1101/2021.05.08.21256881 Date: 2021-05-12 Source: medRxiv

    The possible faecal-oral transmission of SARS-CoV-2 through domestic discharges has emerged as a serious public health concern. Based on persistence of the virus in environment, the wastewater-based epidemiology (WBE) enabled the surveillance of infection in a community. The water bodies connected to the anthropogenic activities have strong possibility of presence of the SARS-CoV-2 genetic material. In this work, we monitored urban, peri-urban and rural lakes in and around Hyderabad as a long-term surveillance study for presence of enteric virus SARS-CoV-2 gene fragments. The study time of seven months coincided with the first and second wave of COVID-19 MESHD infection. The study depicted differential viral RNA copies in the urban lake with high viral load observed during the peaks of wave I and wave II. Distinct variability in viral genes detection was observed amongst all five lakes which were in concordance with the human activity of the catchment area. The SARS-CoV-2 genes were not detected in peri-urban and rural lakes, whereas the urban lakes having direct functional attributes from domestic activity, in the community showed presence of viral load. The outcome of the study clearly shows that the urban water streams linked with domestic discharge will function as a proxy for wastewater epidemiological studies. The surge in viral gene load from February 2021 sample suggests the on shoot of the second wave of infection, which correlated well with the prevailing pandemic situation. Implementation of regular WBE based monitoring system for the water bodies/wastewater in the urban and semi-urban areas will help to understand the outbreak and spread of virus in the community.

    Clinical outcomes and cost-effectiveness of COVID-19 MESHD vaccination in South Africa

    Authors: Krishna P Reddy; Kieran P Fitzmaurice; Justine A Scott; Guy Harling; Richard J Lessells; Christopher Panella; Fatma M Shebl; Kenneth A Freedberg; Mark J Siedner

    doi:10.1101/2021.05.07.21256852 Date: 2021-05-12 Source: medRxiv

    Low- and middle-income countries are implementing COVID-19 MESHD vaccination strategies in light of varying and uncertain vaccine efficacies and costs, supply shortages, and resource constraints. We used a microsimulation model to evaluate clinical outcomes and cost-effectiveness of a COVID-19 MESHD vaccination program in South Africa. We varied vaccination coverage, pace, acceptance, effectiveness, and cost as well as epidemic dynamics. Providing vaccine to at least 40% of the population and prioritizing accelerated vaccine rollout prevented >9 million infections and >73,000 deaths and reduced costs due to fewer hospitalizations. Further, the vaccination program was cost-saving even at the lowest examined levels of acceptance (50%), effectiveness against infection (20%), effectiveness against symptomatic disease (30%), and effectiveness against severe/ critical disease MESHD requiring hospitalization (40%), and with vaccination costs of up to USD25/person. In summary, a COVID-19 MESHD vaccination program would reduce both deaths MESHD and health care costs in South Africa across a wide range of assumptions. Vaccination program implementation factors, including prompt procurement, distribution, and rollout, are likely more influential than characteristics of the vaccine itself in maximizing public health benefits and economic efficiency.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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