Testosterone and COVID-19 — a stone in the way

Abstract

This letter highlights the relevance of investigating the potential connection between testosterone and SARS-CoV-2 infection to support the comprehension of the COVID-19 pathophysiological outcome. The relationship converges since SARS-CoV-2 has a virulence mechanism, the Spike glycoprotein, that mediates viral entry by binding to ACE2 on the epithelial cell surface, a process supported by transmembrane protease serine 2 (TMPRSS2) (Osuchowski et al. 2021). Therefore, the co-expression of TMPRSS2 and ACE2 is required to ensure viral infection.Interestingly, the TMPRSS2 transmembrane protease gene transcription is stimulated by the nuclear androgenic receptor and the Prostatic Specifi c Antigen (PSA) (Afar et al. 2001). This receptor plays a function in several tissues, being expressed in the adult heart, lung, brain, and fetus liver, in addition to a tangible expression in the prostate (Vaarala 2001). TMPRSS2 has a wellestablished role in some viral infections, such as H7N9 Infl uenza, some Coronaviridae family viruses, furthermore neoplasms, for example, in prostate cancer and metastases (Lucas et al. 2014).