Older persons are more susceptible to infection due to the age-related immunologic changes and the state of constitutive lowgrade inflammation. The rate of complications from the novel severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) and its related coronavirus disease 2019 (COVID-19), is significantly higher in the elderly, with men as the most affected. It is known that women, in general, are less susceptible to viral infections complications thanks to three main differences in sex chromosomes, innate immunity, and steroid hormones. COVID-19 epidemiology in Italy further support that older women, even if frailer, may experience lower mortality than men, which extends the ‘male-female health-survival paradox’ to acutely ill patient groups.