Corpus overview


Overview

MeSH Disease

HGNC Genes

There are no HGNC terms in the subcorpus


Transmission

There are no transmission terms in the subcorpus


Seroprevalence

There are no seroprevalence terms in the subcorpus

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    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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