Background Given that an individual’s age and gender are strongly predictive of coronavirus disease 2019 (COVID-19) outcomes, do such factors imply anything about preferable therapeutic options? Methods An analysis of electronic health records for a large (68,466-case), international COVID-19 cohort, in 5-year age strata, revealed age-dependent sex differences. In particular, we surveyed the effects of systemic hormone administration in women. The primary outcome for estradiol therapy was death. Odds ratios (ORs) and Kaplan-Meier survival curves were analyzed for 37,086 COVID-19 women in two age groups: pre- (15–49 years) and peri-/post-menopausal (> 50 years). Results The incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is higher in women than men (by about + 15%) and, in contrast, the fatality rate is higher in men (about + 50%). Interestingly, the relationships between these quantities are linked to age: pre-adolescent girls and boys had the same risk of infection and fatality rate, while adult premenopausal women had a significantly higher risk of infection than men in the same 5-year age stratum (about 16,000 vs. 12,000 cases). This ratio changed again in peri- and postmenopausal women, with infection susceptibility converging with men. While fatality rates increased continuously with age for both sexes, at 50 years, there was a steeper increase for men. Thus far, these types of intricacies have been largely neglected. Because the hormone 17ß-estradiol influences expression of the human angiotensin-converting enzyme 2 (ACE2) protein, which plays a role in SARS-CoV-2 cellular entry, propensity score matching was performed for the women’s sub-cohort, comparing users vs. non-users of estradiol. This retrospective study of hormone therapy in female COVID-19 patients shows that the fatality risk for women > 50 years receiving estradiol therapy (user group) is reduced by more than 50%; the OR was 0.33, 95% CI [0.18, 0.62] and the hazard ratio (HR) was 0.29, 95% CI [0.11,0.76]. For younger, pre-menopausal women (15–49 years), the risk of COVID-19 fatality is the same irrespective of estradiol treatment, probably because of higher endogenous estradiol levels. Conclusions As of this writing, still no effective drug treatment is available for COVID-19; since estradiol shows such a strong improvement regarding fatality in COVID-19, we suggest prospective studies on the potentially more broadly protective roles of this naturally occurring hormone. Supplementary Information The online version contains supplementary material available at 10.1186/s12916-020-01851-z.
【저자키워드】 COVID-19, SARS-CoV-2, ACE2, Sex, estradiol, women, Hormone treatment, 【초록키워드】 Treatment, coronavirus disease, coronavirus, therapy, susceptibility, Prospective Study, Infection, risk, Electronic health record, outcomes, Retrospective study, Protein, International, therapeutic, female, death, age, cellular entry, incidence, expression, fatality, administration, Analysis, propensity score matching, risk of infection, COVID-19 patient, Predictive, acute respiratory syndrome, Factor, Primary outcome, supplementary material, 95% CI, hazard ratio, human Angiotensin-converting enzyme, Fatality rate, protective role, both sexes, while, COVID-19 cohort, Effect, men, risk of COVID-19, effective, Kaplan-Meier survival curve, Result, analyzed, receiving, was performed, reduced, significantly higher, changed, influence, age and gender, estradiol therapy, pre-menopausal women, sub-cohort, 【제목키워드】 Treatment, SARS-COV-2 infection,