The Physiological Mechanisms of the Sex-Based Difference in Outcomes of COVID19 Infection

Overview

Journal Front Physiol

Date 2021 Feb 26

PMID 33633588

Citations 20

Authors

Susan Wray

Sarah Arrowsmith

Affiliations

Soon will be listed here.

Abstract

The scale of the SARS-CoV-2 pandemic has thrust a spotlight on the sex-based differences in response to viral diseases; morbidity and mortality are greater in men than women. We outline the mechanisms by which being female offers a degree of protection from COVID19, that persists even when confounders such as comorbidities are considered. The physiological and immunological mechanisms are fascinating and range from incomplete X chromosome inactivation of immune genes, a crucial role for angiotensin converting enzyme 2 (ACE2), and regulation of both immune activity and ACE2 by sex steroids. From this flows understanding of why lung and other organs are more susceptible to COVID19 damage in men, and how their distinct immunological landscapes need to be acknowledged to guide prognosis and treatment. Pregnancy, menopause, and hormone replacement therapy bring changed hormonal environments and the need for better stratification in COVID19 studies. We end by noting clinical trials based on increasing estrogens or progesterone or anti-testosterone drugs; excellent examples of translational physiology.

Citing Articles

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Estradiol and Dihydrotestosterone Levels in COVID-19 Patients.

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Does comorbidity burden explain the higher COVID-19 mortality risk among men? A retrospective cross-sectional analysis of a well-defined cohort of patients in Bronx, New York.

Vasa A, Kini M, Neugarten J, Bellin E, Golestaneh L BMJ Open. 2022; 12(9):e063862.

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Androgen receptor polyQ alleles and COVID-19 severity in men: A replication study.

Lopez-Rodriguez R, Ruiz-Hornillos J, Corton M, Almoguera B, Minguez P, Perez-Tomas M Andrology. 2022; 11(1):24-31.

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