4.6 Review

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

Journal

NATURE REVIEWS ENDOCRINOLOGY
Volume 19, Issue 4, Pages 217-231

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41574-022-00780-6

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This review summarizes the roles of androgens, estrogens, and progesterone in the regulation of virus entry receptors and disease progression of COVID-19, as well as their therapeutic value. Currently, there is no clear evidence for a sex-specific expression of virus entry receptors, and the impact of sex hormones on COVID-19 varies widely. The conflicting evidence and lack of consensus may be due to a lack of mechanistic studies and clinical trials reporting sex-disaggregated data. Furthermore, the influence of sociocultural factors (gender) on COVID-19 manifestations has not been investigated.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a clear sex disparity in clinical outcomes. Hence, the interaction between sex hormones, virus entry receptors and immune responses has attracted major interest as a target for the prevention and treatment of SARS-CoV-2 infections. This Review summarizes the current understanding of the roles of androgens, oestrogens and progesterone in the regulation of virus entry receptors and disease progression of coronavirus disease 2019 (COVID-19) as well as their therapeutic value. Although many experimental and clinical studies have analysed potential mechanisms by which female sex hormones might provide protection against SARS-CoV-2 infectivity, there is currently no clear evidence for a sex-specific expression of virus entry receptors. In addition, reports describing an influence of oestrogen, progesterone and androgens on the course of COVID-19 vary widely. Current data also do not support the administration of oestradiol in COVID-19. The conflicting evidence and lack of consensus results from a paucity of mechanistic studies and clinical trials reporting sex-disaggregated data. Further, the influence of variables beyond biological factors (sex), such as sociocultural factors (gender), on COVID-19 manifestations has not been investigated. Future research will have to fill this knowledge gap as the influence of sex and gender on COVID-19 will be essential to understanding and managing the long-term consequences of this pandemic.

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