Is Sex a Determinant of COVID-19 Infection? Truth or Myth?

Accumulating clinical evidence demonstrates that the intensity of the infection and its complications are more prominent in men. It has been postulated that potential functional modulation of ACE2 by estrogen may explain the sex difference in morbidity and mortality. We review here the evidence regarding the role of estrogenic hormones in ACE2 expression and regulation, with the intent of bringing to the forefront potential mechanisms that may explain sex differences in SARS-CoV-2 infection and COVID-19 outcomes, assist in management of COVID-19, and uncover new therapeutic strategies.