Gender susceptibility to COVID-19: a review of the putative role of sex hormones and X chromosome.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic hypotheses and secondary epidemiological data without original clinical trials or systematic review methodology.
PubMed 32936429 · doi:10.1007/s40618-020-01383-6
What was done
The authors conducted a narrative review summarizing literature on biological, genetic, and endocrine mechanisms underlying sex differences in COVID-19 susceptibility, focusing on ACE2 and TMPRSS2 regulation.
What was found
Citing Italian surveillance data on 239,709 patients, males had a lower infection rate than females (45.8% vs 54.2%) but higher lethality (17.7% in men vs 10.8% in women), representing 59% of total deaths. The authors hypothesize that female protection arises from higher ACE2 expression (via estrogens or X-chromosome mechanisms) maintaining renin-angiotensin system balance, combined with lower androgen levels keeping TMPRSS2 expression low to impede viral entry.
Why it matters
This review integrates endocrine and genetic hypotheses to provide a biological framework for why male COVID-19 patients experience higher mortality.
Limits
The review relies on mechanistic reasoning and unadjusted population-level surveillance data rather than new experimental or clinical measurements. It does not provide systematic search methods or study counts, and confounding factors such as age and comorbidities are not controlled for in the cited figures.
Cited by
- context The ACE2 gene is located on the X chromosome and escapes X-inactivation, leading to higher ACE2 levels in women.