Do anti-androgens have potential as therapeutics for COVID-19?

Mauvais-Jarvis, Franck

COVID-19 is characterized by a gender disparity in severity, with men exhibiting higher hospitalization and mortality rates than women. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, infects cells following recognition and attachment of the viral spike (S) glycoprotein to the angiotensin-converting enzyme 2 (ACE2) transmembrane protein, followed by spike protein cleavage and activation by cell surface transmembrane protease serine 2 (TMPRSS2). In prostate cancer cells, androgen acting on the androgen receptor (AR) increases TMPRSS2 expression, which has led to the hypothesis that androgen-dependent expression of TMPRSS2 in the lung, may increase men’s susceptibility to severe COVID-19 and that, accordingly, suppressing androgen production or action may mitigate COVID-19 severity by reducing SARS-CoV-2 amplification. Several ongoing clinical trials are testing the ability of androgen deprivation therapies (ADT) or anti-androgens to mitigate COVID-19.This perspective discusses clinical and molecular advances on the rapidly evolving field of AR action on TMPRSS2 expression and SARS-COV-2 infection, and the potential effect of anti-androgens on COVID-19 severity in male patients. It discusses limitations of current studies and offer insight for future directions.