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Overview

MeSH Disease

HGNC Genes

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Transmission

Seroprevalence
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    Alzheimer's MESHD and Parkinson's diseases MESHD predict different COVID-19 MESHD outcomes, a UK Biobank study

    Authors: Yizhou Yu; Marco Travaglio; Rebeka Popovic; Nuno Santos Leal; L. Miguel Martins; Arijit Chakravarty; Kayleigh J Mason; Helen McAteer; Freya Meynall; Bolaji Coker; Alexandra Vincent; Dominic Urmston; Amber Vesty; Jade Kelly; Camille Lancelot; Lucy Moorhead; Herve Bachelez; Ian N Bruce; Francesca Capon; Claudia Romina Contreras; Andrew P Cope; Claudia De La Cruz; Paola Di Meglio; Paolo Gisondi; Kimme Hyrich; Denis Jullien; Jo Lambert; Hoseah Waweru; Helena Marzo-Ortega; Iain McInnes; Luigi Naldi; Sam Norton; Lluis Puig; Phyllis Spuls; Raj Sengupta; Tiago Torres; RIchard B Warren; John Weinman; Christopher EM Griffiths; Jonathan N Barker; Matthew A Brown; James B Galloway; Catherine H Smith

    doi:10.1101/2020.11.05.20226605 Date: 2020-11-07 Source: medRxiv

    In December 2019, a coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began infecting humans causing a novel disease, coronavirus disease MESHD 19 ( COVID-19 MESHD). This was first described in the Wuhan province of the People's Republic of China. SARS-CoV-2 spread throughout the world causing a global pandemic. To date, thousands of cases of COVID-19 MESHD were reported in the United Kingdom, and over 45,000 patients have died. Some progress has been achieved in managing this disease, but the biological determinants of health, besides age TRANS, that affect COVID-19 MESHD infectivity and mortality are under scrutiny. Recent studies show that several medical conditions, including diabetes MESHD and hypertension MESHD hypertension HP, increase the risk of COVID-19 MESHD infection and death. The increased vulnerability of the elderly TRANS and those with comorbidities, together with the prevalence SERO of neurodegenerative diseases MESHD with advanced age TRANS, led us to investigate the links between neurodegeneration HP neurodegeneration MESHD and COVID-19 MESHD. We analysed the primary health records of 13,338 UK individuals tested for COVID-19 MESHD between March and July 2020. We show that a pre-existing diagnosis of Alzheimer's disease MESHD predicts the highest risk of COVID-19 MESHD infection and mortality among the elderly TRANS. In contrast, Parkinson's disease MESHD patients were found to be at increased risk of infection TRANS but not mortality from COVID-19 MESHD. We conclude that there are disease-specific differences in COVID-19 MESHD susceptibility among patients affected by neurodegenerative disorders MESHD.

    Analysis of Genetic Host Response Risk Factors in Severe COVID-19 MESHD Patients

    Authors: Krystyna Taylor; Sayoni Das; Matthew Pearson; James Kozubek; Marcin Pawlowski; Claus Erik Jensen; Zbigniew Skowron; Gert Lykke Møller; Mark Strivens; Steve Gardner

    doi:10.1101/2020.06.17.20134015 Date: 2020-06-19 Source: medRxiv

    BACKGROUND Epidemiological studies indicate that as many as 20% of individuals who test positive for COVID-19 MESHD develop severe symptoms that can require hospitalization. These symptoms include low platelet count, severe hypoxia MESHD, increased inflammatory cytokines and reduced glomerular filtration rate. Additionally, severe COVID-19 MESHD is associated with several chronic co-morbidities, including cardiovascular disease MESHD, hypertension MESHD hypertension HP and type 2 diabetes mellitus MESHD diabetes mellitus HP. The identification of genetic risk factors that impact differential host responses to SARS-CoV-2, resulting in the development of severe COVID-19 MESHD, is important in gaining greater understanding into the biological mechanisms underpinning life-threatening responses to the virus. These insights could be used in the identification of high-risk individuals and for the development of treatment strategies for these patients. METHODS As of June 6, 2020, there were 976 patients who tested positive for COVID-19 MESHD and were hospitalized, indicating they had a severe response to SARS-CoV-2. There were however too few patients with a mild form of COVID-19 MESHD to use this cohort as our control population. Instead we used similar control criteria to our previous study looking at shared genetic risk factors between severe COVID-19 MESHD and sepsis MESHD sepsis HP, selecting controls who had not developed sepsis HP sepsis MESHD despite having maximum co-morbidity risk and exposure to sepsis HP sepsis MESHD-causing pathogens. RESULTS Using a combinatorial (high-order epistasis) analysis approach, we identified 68 protein-coding genes that were highly associated with severe COVID-19 MESHD. At the time of analysis, nine of these genes have been linked to differential response to SARS-CoV-2. We also found many novel targets that are involved in key biological pathways associated with the development of severe COVID-19 MESHD, including production of pro-inflammatory cytokines, endothelial cell dysfunction, lipid droplets, neurodegeneration HP neurodegeneration MESHD and viral susceptibility factors. CONCLUSION The variants we found in genes relating to immune response pathways and cytokine production cascades, were in equal proportions across all severe COVID-19 MESHD patients, regardless of their co-morbidities. This suggests that such variants are not associated with any specific co-morbidity, but are common amongst patients who develop severe COVID-19 MESHD. Among the 68 severe COVID-19 MESHD risk-associated genes, we found several druggable protein targets and pathways. Nine are targeted by drugs that have reached at least Phase I clinical trials, and a further eight have active chemical starting points for novel drug development. Several of these targets were particularly enriched in specific co-morbidities, providing insights into shared pathological mechanisms underlying both the development of severe COVID-19 MESHD, ARDS and these predisposing co-morbidities. We can use these insights to identify patients who are at greatest risk of contracting severe COVID-19 MESHD and develop targeted therapeutic strategies for them, with the aim of improving disease burden and survival rates.

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MeSH Disease
HGNC Genes
Transmission
Seroprevalence


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