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Gender and genetic factors impacting COVID-19 severity.

ABSTRACT: COVID-19 pandemic is a cause of global concern and is impacting lives and economy globally. Infection due to SARS-CoV-2 leads to varied clinical manifestations, which can vary from asymptomatic to severe acute respiratory syndrome and death. The clinical features are proposed to depend upon various host factors, namely, gender and genetic factors. The significantly high mortality among males has revealed the role of gender, androgens, age, genetics, and risk factors in determining the severity of COVID-19 among the population. The interplay of various host factors and their association with clinically severe infections is crucial for our understanding of COVID-19 pathogenesis. A PubMed and Google scholar search was made using keywords such as "COVID-19 + sex differences," "COVID-19 + androgens," "COVID-19 + ACE2 receptor," and "COVID-19 + smoking alcoholism pregnancy." The articles which highlight the association of gender and genetic factors to COVID-19 were selected and included in our study. It is mainly the primary care or family physicians who act as the first contact of COVID-19 patients. With the recent increase in SARS-CoV-2 infections in the Indian subcontinent and probability of upcoming surges, it has become imperative to understand its interaction with the various gender and genetic factors to devise effective triage and management protocols. Our review highlights the possible mechanisms by which these factors impact the severity of COVID-19. A better understanding of these factors will be of immense help to primary care physicians.

SUBMITTER: Ranjan J

PROVIDER: S-EPMC8797126 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Gender and genetic factors impacting COVID-19 severity.

Ranjan Jai J Ravindra Akshatha A Mishra Baijayantimala B

Journal of family medicine and primary care 20211129 11

COVID-19 pandemic is a cause of global concern and is impacting lives and economy globally. Infection due to SARS-CoV-2 leads to varied clinical manifestations, which can vary from asymptomatic to severe acute respiratory syndrome and death. The clinical features are proposed to depend upon various host factors, namely, gender and genetic factors. The significantly high mortality among males has revealed the role of gender, androgens, age, genetics, and risk factors in determining the severity o ...[more]

PMID: 35136752

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Project description:Using RNA-seq and high-resolution mass spectrometry we performed a comprehensive systems analysis on 128 plasma and leukocyte samples from hospitalized patients with or without COVID-19 (n=102 and 26 respectively) and with differing degrees of disease severity. We generated abundance measurements for over 17,000 transcripts, proteins, metabolites, and lipids and compiled them with clinical data into a curated relational database. This resource offers the unique opportunity to perform systems analysis and cross-ome correlations to both molecules and patient outcomes. In total 219 molecular features were mapped with high significance to COVID-19 status and severity, including those involved in processes such as complement system activation, dysregulated lipid transport, and B cell activation. In one example, we detected a trio of covarying molecules – citrate, plasmenyl-phosphatidylcholines, and gelsolin (GSN) – that offer both pathophysiological insight and potential novel therapeutic targets. Further, our data revealed in some cases, and supported in others, that several biological processes were dysregulated in COVID-19 patients including vessel damage, platelet activation and degranulation, blood coagulation, and acute phase response. For example, we observed that the coagulation-related protein, cellular fibronectin (cFN), was highly increased within COVID-19 patients and provide new evidence that the upregulated proteoform stems from endothelial cells, consistent with endothelial injury as a major activator of the coagulation cascade. The abundance of prothrombin, which is cleaved to form thrombin during clotting, was significantly reduced and correlated with severity and might help to explain the hyper coagulative environment of SARS-CoV-2 infection. From transcriptomic analysis of leukocytes, we concluded that COVID-19 patients with acute respiratory distress syndrome (ARDS) demonstrated a phenotype that overlapped with, but was distinct from, that found in patients with non-COVID-19-ARDS. To aid in the global efforts toward elucidation of disease pathophysiology and therapeutic development, we created a web-based tool with interactive visualizations allowing for easy navigation of this systems-level compendium of biomolecule abundance in relation to COVID-19 status and severity. Finally, we leveraged these multi-omic data to predict COVID-19 patient outcomes with machine learning, which highlighted the predictive power of these expansive molecular measurements beyond the standardized clinical estimate of 10-year survival Charlson score.

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Gender and genetic factors impacting COVID-19 severity.

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Gender and genetic factors impacting COVID-19 severity.

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