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Review
. 2022 Mar 4;13(1):7.
doi: 10.1186/s13293-022-00417-3.

Immune mechanisms associated with sex-based differences in severe COVID-19 clinical outcomes

Cosby G Arnold  1 , Anne Libby  2 , Alexis Vest  2 , Andrew Hopkinson  2 , Andrew A Monte  2
Affiliations
Review

Immune mechanisms associated with sex-based differences in severe COVID-19 clinical outcomes

Cosby G Arnold et al. Biol Sex Differ. .

Abstract

Background: Although biological males and females are equally likely to become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), evidence has mounted that males experience higher severity and fatality compared to females. MAIN: The objective of this review is to examine the existing literature on biological mechanisms underlying sex-based differences that could contribute to SARS-CoV-2 infection clinical outcomes. Sex-based differences in immunologic response and hormonal expression help explain the differences in coronavirus disease 2019 (COVID-19) outcomes observed in biological males and females. X inactivation facilitates a robust immune response to COVID-19 in females, who demonstrate a more profound antibody response and faster recovery when compared to males. Low testosterone levels also help explain the dysregulated inflammatory response and poor outcomes observed in some males with COVID-19. Gender differences in health expression and behaviors further compound these observed differences.

Conclusion: Understanding the biology of sex-based differences in COVID-19 severity and mortality could help inform preventative measures, treatment decisions, and development of personalized, sex-specific therapies.

Keywords: COVID-19; Gender; SARS-CoV-2; Sex.

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Conflict of interest statement

The authors declare that they do not have any competing interest.

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