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COVID-19 pandemic: insights into molecular mechanisms leading to sex-based differences in patient outcomes

Part of: Molecular understanding of Covid pathogenesis, immunity and therapeutics

Published online by Cambridge University Press:  03 August 2021

Ashutosh Kumar Open the ORCID record for Ashutosh Kumar [Opens in a new window] ,
Ravi K. Narayan ,
Maheswari Kulandhasamy ,
Pranav Prasoon ,
Chiman Kumari ,
Sujeet Kumar ,
Vikas Pareek ,
Kishore Sesham ,
Prakash S. Shekhawat  and
Kamla Kant
...Show all authors
Ashutosh Kumar*
Affiliation:
Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India Department of Anatomy, All India Institute of Medical Sciences (AIIMS), Patna, India
Ravi K. Narayan
Affiliation:
Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India Department of Anatomy, All India Institute of Medical Sciences (AIIMS), Patna, India
Maheswari Kulandhasamy
Affiliation:
Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India Department of Biochemistry, Maulana Azad Medical College (MAMC), New Delhi, India
Pranav Prasoon
Affiliation:
Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India Pittsburgh Center for Pain Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
Chiman Kumari
Affiliation:
Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India Department of Anatomy, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Sujeet Kumar
Affiliation:
Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India Centre for Proteomics and Drug Discovery, Amity Institute of Biotechnology, Amity University, Mumbai, Maharashtra, India
Vikas Pareek
Affiliation:
Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India Centre for Cognitive and Brain Sciences, Indian Institute of Technology, Gandhinagar, Gujarat, India
Kishore Sesham
Affiliation:
Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India Department of Anatomy, All India Institute of Medical Sciences (AIIMS), Mangalagiri, Andhra Pradesh, India
Prakash S. Shekhawat
Affiliation:
Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India Department of Hematology, Nil Ratan Sircar Medical College and Hospital (NRSMCH), Kolkata, India
Kamla Kant
Affiliation:
Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India Department of Microbiology, All India Institute of Medical Sciences (AIIMS), Bathinda, India
Santosh Kumar
Affiliation:
Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, USA
*
Author for correspondence: Ashutosh Kumar, E-mail: drashutoshkumar@aiimspatna.org
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Abstract

Recent epidemiological studies analysing sex-disaggregated patient data of coronavirus disease 2019 (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 molecular mechanisms leading to 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 conducted 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 unravelled 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.

Keywords

COVID-19epigenetic mechanismsevolutiongeneticsSARS-CoV-2sexsex hormones
Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 23 , 2021 , e7
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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