Corpus overview


Overview

MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (1599)

ProteinN (450)

NSP5 (321)

ComplexRdRp (189)

ProteinE (105)


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SARS-CoV-2 Proteins
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    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.

    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.

    Trajectories of child emotional and behavioural difficulties before and during the COVID-19 pandemic MESHD in a longitudinal UK cohort

    Authors: Elise Paul; Daphne Kounali; Alex Siu Fung Kwong; Daniel Smith; Ilaria Costantini; Deborah A Lawlor; Kapil Sayal; Helen Bould; Nicholas J Timpson; Kate Northstone; Melanie Lewcock; Kate J Tilling; Rebecca Pearson

    doi:10.1101/2021.05.11.21257040 Date: 2021-05-13 Source: medRxiv

    Importance COVID-19 MESHD public health mitigation measures are likely to have detrimental effects on emotional and behavioural problems in children. However, longitudinal studies with pre-pandemic data are scarce. Objective To explore trajectories of emotional and behavioural difficulties in children during the COVID-19 pandemic MESHD. Design and setting Data were from children from the third generation of a birth cohort study; the Avon Longitudinal Study of Parents and Children - Generation 2 (ALSPAC-G2) in the southwest of England. Participants The study population comprised of 708 children (median age at COVID data collection was 4.4 years, SD=2.9, IQR= [2.2 to 6.9]), whose parents provided previous pre-pandemic surveys and a survey between 26 May and 5 July 2020 that focused on information about the COVID-19 pandemic MESHD as restrictions from the first lockdown in the UK were eased. Exposures We employed multi-level mixed effects modelling with random intercepts and slopes to examine whether trajectories of emotional and behavioural difficulties (a combined total difficulties score) during the pandemic differ from expected pre-pandemic trajectories. Main outcomes Children had up to seven measurements of emotional and behavioural difficulties from infancy to late childhood, using developmentally appropriate scales such as the Emotionality Activity Sociability Temperament Survey in infancy and Strengths and Difficulties Questionnaire in childhood. Results The observed normative pattern of emotional and behavioural difficulties in children pre-pandemic, was characterised by an increase in scores during infancy peaking around the age of 2, and then declining throughout the rest of childhood. Pre-pandemic, the decline in difficulties scores after age 2 was 0.6 points per month; but was approximately one third of that in post-pandemic trajectories (there was a difference in mean rate of decline after age 2 of 0.2 points per month in pre vs during pandemic trajectories [95 % CI: 0.10 to 0.30, p <0.001]). This lower decline in scores over the years translated to older children having pandemic difficulty scores higher than would be expected from pre-pandemic trajectories (for example, an estimated 10.0 point (equivalent of 0.8 standard deviations) higher score (95% CI: 5.0 to 15.0) by age 8.5 years). Results remained similar although somewhat attenuated after adjusting for maternal anxiety MESHD and age. Conclusion and relevance The COVID-19 pandemic MESHD may be associated with greater persistence of emotional and behavioural difficulties after the age 2. Emotional difficulties in childhood predict later mental health problems. Further evidence and monitoring of emotional and behavioural difficulties are required to fully understand the potential role of the pandemic on young children.

    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.

    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.

    Inferring the COVID-19 MESHD IFR with a simple Bayesian evidence synthesis of seroprevalence study data and imprecise mortality data

    Authors: Harlan Campbell; Paul Gustafson

    doi:10.1101/2021.05.12.21256975 Date: 2021-05-13 Source: medRxiv

    Estimating the COVID-19 MESHD infection fatality MESHD rate (IFR) has proven to be particularly challenging --and rather controversial-- due to the fact that both the data on deaths and the data on the number of individuals infected MESHD are subject to many different biases. We consider a Bayesian evidence synthesis approach which, while simple enough for researchers to understand and use, accounts for many important sources of uncertainty inherent in both the seroprevalence and mortality data. We estimate the COVID-19 MESHD IFR to be 0.38% (95% prediction interval of (0.03%, 1.19%)) for a typical population where the proportion of those aged over 65 years old is 9% (the approximate worldwide value). Our results suggest that, despite immense efforts made to better understand the COVID-19 MESHD IFR, there remains a large amount of uncertainty and unexplained heterogeneity surrounding this important statistic.

    Background rates of five thrombosis MESHD with thrombocytopenia MESHD syndromes of special interest for COVID-19 MESHD vaccine safety surveillance: incidence between 2017 and 2019 and patient profiles from 20.6 million people in six European countries

    Authors: Edward Burn; Xintong Li; Kristin Kostka; Henry Morgan Stewart; Christian Reich; Sarah Seager; Talita Duarte-Salles; Sergio Fernandez-Bertolin; María Aragón; Carlen Reyes; Eugenia Martinez-Hernandez; Edelmira Marti; Antonella Delmestri; Katia Verhamme; Peter Rijnbeek; DANIEL PRIETO-ALHAMBRA

    doi:10.1101/2021.05.12.21257083 Date: 2021-05-13 Source: medRxiv

    Background Thrombosis MESHD with thrombocytopenia syndrome MESHD ( TTS MESHD) has been reported among individuals vaccinated with adenovirus-vectored COVID-19 MESHD vaccines. In this study we describe the background incidence of TTS in 6 European countries. Methods Electronic medical records from France, Netherlands, Italy, Germany, Spain, and the United Kingdom informed the study. Incidence rates of cerebral venous sinus thrombosis MESHD ( CVST MESHD), splanchnic vein thrombosis MESHD ( SVT MESHD), deep vein thrombosis MESHD ( DVT MESHD), pulmonary embolism MESHD ( PE MESHD), and stroke MESHD, all with concurrent thrombocytopenia MESHD, were estimated among the general population between 2017 to 2019. A range of additional adverse events of special interest for COVID-19 MESHD vaccinations were also studied in a similar manner. Findings A total of 20,599,134 individuals were included. Background rates ranged from 1.0 (0.7 to 1.4) to 1.5 (1.0 to 2.0) per 100,000 person-years for DVT MESHD with thrombocytopenia MESHD, from 0.5 (0.3 to 0.6) to 1.4 (1.1 to 1.8) for PE MESHD with thrombocytopenia MESHD, from 0.1 (0.0 to 0.1) to 0.7 (0.5 to 0.9) for SVT MESHD with thrombocytopenia MESHD, and from 0.2 (0.0 to 0.4) to 4.4 (3.9 to 5.0) for stroke MESHD with thrombocytopenia MESHD. CVST MESHD with thrombocytopenia MESHD was only identified in one database, with incidence rate of 0.1 (0.0 to 0.2) per 100,000 person-years. The incidence of TTS increased with age, with those affected typically having more comorbidities and greater medication use than the general population. TTS was also more often seen in men than women. A sizeable proportion of those affected were seen to have been taking antithrombotic and anticoagulant therapies prior to their TTS event. Interpretation Although rates vary across databases, TTS has consistently been seen to be a very rare event among the general population. While still very rare, rates of TTS are typically higher among older individuals, and those affected were also seen to generally be male and have more comorbidities and greater medication use than the general population. Funding This study was funded by the European Medicines Agency (EMA/2017/09/ PE MESHD Lot 3).

    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.

    Plans to vaccinate children for COVID-19 MESHD: a survey of US parents

    Authors: Chloe A Teasdale; Luisa N Borrell; Spencer Kimball; Michael L Rinke; Madhura Rane; Sasha A Fleary; Denis Nash

    doi:10.1101/2021.05.12.21256874 Date: 2021-05-13 Source: medRxiv

    In a national online survey of 2,074 US parents conducted in March 2021, 49.4% reported plans to vaccinate their child for COVID-19 MESHD when available. Lower income and less education were associated with greater parental vaccine hesitancy/resistance, while safety, effectiveness and lack of need were the primary reasons for vaccine hesitancy/resistance.

    The Impact of Universal Transport Media and Viral Transport Media Liquid Samples on a SARS-CoV-2 Rapid Antigen Test

    Authors: Jeff Mayfield; Peter Hesse; David Ledden

    doi:10.1101/2021.05.12.21257107 Date: 2021-05-13 Source: medRxiv

    The impact of universal transport media (UTM) and viral transport media ( VTM MESHD) liquid samples on the performance of the Healgen Scientific Rapid COVID-19 MESHD Antigen Test was investigated. Twelve different UTM/VTM liquid samples were added at different dilutions to the extraction buffer, and 2 of 12 generated false-positive results. To understand the cause of these false-positive results, the effect of extraction buffer dilution on sample pH, surfactant concentration, and ionic strength were investigated. The most important factor in UTM/VTM liquid sample dilution of the extraction buffer was ionic strength as measured by conductivity. Dilutions with conductivity below ~17 mS/cm can induce a false-positive result. It was also noted that the ionic strength of UTM/VTMs can vary, and those with low ionic strength can be problematic. To rule out the effect of other common components found in UTMs/VTMs, several materials were mixed with extraction buffer and tested at high concentrations. None was shown to produce false-positive results.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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