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Potential Influence of Menstrual Status and Sex Hormones on female SARS-CoV-2 Infection: A Cross-sectional Study from Multicentre in Wuhan, China.

BACKGROUND
Recent studies indicated that females have a lower morbidity, severe cases rate, mortality and better outcome than those of male. However, it remained to be addressed why this was the case.


METHODS AND FINDINGS
To find the factors that potentially protect females from COVID-19, we recruited all confirmed patients hospitalized at three branches of Tongji Hospital (n=1902) from January 28 to March 8, 2020, and analyzed the correlation between menstrual status (n=509，including 68 from Mobile Cabin Hospital)/female hormones (n=78)/ cytokines related to immunity and inflammation(n=263), and the severity/clinical outcomes in female patients under 60 years of age.Non-menopausal female patients had milder severity and better outcome compared with age-matched men (p<0.01/p<0.01). Menopausal patients had longer hospitalization times than non-menopausal patients ( hazard ratio [HR], 1.91; 95% confidence interval [CI], 1.06-3.46，p= 0.033). Both anti-müllerian hormone (AMH) and estradiol (E2) showed a negative correlation with severity of infection (AHR=0.146/0.304, 95%CI = [0.026-0.824]/[0.092-1.001], p=0.029/0.05). E2 levels were negatively correlated with IL-2R, IL-6, IL-8 and TNFα in luteal phase (Pearson Correlation=-0.592, -0.558, -0.545, -0.623; p=0.033, 0.048, 0.054, 0.023), and with C3 in follicular phase (Pearson Correlation=-0.651; p=0.030).


CONCLUSION
Menopause is an independent risk factor for female COVID-19 patients. AMH and E2 are potential protective factors, negatively correlated with COVID-19's severity, among which E2 is attributed to its regulation of cytokines related to immunity and inflammation. Hormone supplement might be a potential therapy for COVID-19 patients.