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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • COVID-19*
  • Female
  • Humans
  • Immunity
  • Male
  • SARS-CoV-2
  • Sex Characteristics
  • Sex Factors