COVID-19 Pandemic: Insights into Molecular Mechanisms Leading to Sex-based Differences in Patient Outcomes

Abstract

Recent epidemiological studies analyzing sex disaggregated patient data in COVID-19 across the world revealed a distinct sex bias in the disease morbidity as well as the mortality- both being higher for the men. Similar antecedents have been known for the previous viral infections, including from coronaviruses, such as severe acute respiratory syndrome (SARS) and middle-east respiratory syndrome (MERS). A sound understanding of the molecular mechanisms leading the biological sex bias in the survival outcomes of the patients in relation to COVID-19 will act as an essential requisite for developing a sex differentiated approach for therapeutic management of this disease. Recent studies which have explored molecular mechanism(s) behind sex-based differences in COVID-19 pathogenesis are scarce, however, existing evidence, for other respiratory viral infections, viz., SARS, MERS, and influenza, provides important clues in this regard. In attempt to consolidate the available knowledge on this issue, we performed a systematic review of the existing empirical knowledge and recent experimental studies following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The qualitative analysis of the collected data untraveled multiple molecular mechanisms, such as, evolutionary and genetic/epigenetic factors, sex-linkage of viral host cell entry receptor and immune response genes, sex hormone and gut microbiome mediated immune-modulation, as the possible key reasons for the sex-based differences in patient outcomes in COVID-19.

Publication Title

Expert Reviews in Molecular Medicine

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