No evidence that androgen regulation of pulmonary TMPRSS2 explains sex-discordant COVID-19 outcomes

Mehdi Baratchian; Jeff McManus; Mike Berk; Fumihiko Nakamura; Serpil Erzurum; Sanjay Mukhopadhyay; Judy Drazba; John Peterson; Ben Gaston; Nima Sharifi

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.21.051201 doi: bioRxiv preprint clear androgen-dependent effect in prostatic tissues. Pulmonary TMPRSS2 regulation appears not to account for the sex-discordance in COVID-19 clinical outcomes. In contrast, both TMPRSS2 and ACE2 appear to have increased expression in current smokers. It is not yet known whether these changes in expression have a functional impact on COVID-19 infection, but if they do, the results suggest smokers could partly mitigate their increased risk by quitting smoking. This also raises the question of whether other hazards such as high levels of air pollution could have similar effects. Nevertheless, a recent study reports that ACE2 expression is not upregulated by lung disease or exposure to carcinogens (Smith and Sheltzer, 2020) . Together, these data suggest that induction of ACE2, and perhaps TMPRSS2, is mediated by specific types of tissue injury.