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Sex hormones in SARS-CoV-2 susceptibility: key players or confounders?

Nicola Lott1,2, Caroline E Gebhard3, Susan Bengs1,2

  • 1Department of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland.

Nature Reviews. Endocrinology
|December 9, 2022
PubMed

Insights

Sex hormones like androgens and estrogens may influence COVID-19 outcomes, but evidence is conflicting. Further research on sex and gender differences is crucial for understanding and managing the pandemic

Area of Science:

  • Endocrinology
  • Virology
  • Immunology

Background:

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits significant sex disparities in clinical outcomes.
  • Interactions between sex hormones, viral entry receptors, and immune responses are critical for understanding and treating SARS-CoV-2 infections.

Purpose of the Study:

  • To review the current understanding of how androgens, estrogens, and progesterone regulate SARS-CoV-2 entry receptors and influence COVID-19 progression.
  • To evaluate the therapeutic potential of sex hormones in managing COVID-19.

Main Methods:

  • Review of experimental and clinical studies examining sex hormone effects on SARS-CoV-2.
  • Analysis of data on virus entry receptor expression and disease progression in relation to sex hormones.

Main Results:

  • No clear evidence supports sex-specific expression of SARS-CoV-2 entry receptors.
  • Reports on the influence of estrogen, progesterone, and androgens on COVID-19 course are highly variable and often conflicting.
  • Current data do not support the use of estradiol for COVID-19 treatment.

Conclusions:

  • Conflicting evidence and lack of consensus stem from insufficient mechanistic studies and clinical trials with sex-disaggregated data.
  • The impact of sociocultural factors (gender) on COVID-19 manifestations remains under-investigated.
  • Future research must address sex and gender influences to effectively manage the long-term consequences of the pandemic.

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