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.

Chemotherapy-induced ovarian aging not only increases the risk for early menopause-related complications but also results in infertility in young female cancer survivors. Oogonial stem cells have the ability to generate new oocytes and thus provide new opportunities for treating ovarian aging and female infertility. Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a natural phenol derived from plants, that has been shown to have positive effects on longevity and redox flow in lipid metabolism and a preventive function against certain tumors. To evaluate whether resveratrol could promote the repair of oogonial stem cells damage in a busulfan/cyclophosphamide (Bu/Cy)-induced accelerated ovarian aging model, female mice were administered 30 and 100 mg/kg/d resveratrol through a gavage for 2 weeks. We demonstrated that resveratrol (30 mg/kg/d) relieved oogonial stem cells loss and showed an attenuating effect on Bu/Cy-induced oxidative apoptosis in mouse ovaries, which may be attributed to the attenuation of oxidative levels in ovaries. Additionally, we also showed that Res exerted a dose-dependent effect on oogonial stem cells and attenuated H 2 O 2 -induced cytotoxicity and oxidative stress injury by activating Nrf2 in vitro . Therefore, resveratrol could be of a potential therapeutic drug used to prevent chemotherapy-induced ovarian aging.