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

In addition to male sex, smoking is a risk factor for COVID-19 susceptibility and poor clinical outcomes . One recent study of 1,099 COVID-19-positive patients reported a more than two-fold increased risk for intensive care unit admission and death in smokers as compared with non-smokers (Guan et al., 2020) . We identified human expression GEO datasets of bronchial/airway epithelial cells containing subject smoking status and asked whether smoking is associated with TMPRSS2 expression. Our analysis indicated a consistent pattern where expression of both TMPRSS2 (Fig. 3A ) and the primary SARS-CoV-2 receptor ACE2 ( Fig.3B ) was modestly but significantly increased in smokers compared with non-smokers. Interestingly, the levels were downregulated to never-smoker levels in former smokers. The results of our analysis are in keeping with several recent reports on ACE2 and smoking (Brake et al., 2020; Leung et al., 2020; Smith and Sheltzer, 2020) .