Testosterone in COVID-19: An Adversary Bane or Comrade Boon

Abstract

COVID-19 is a pandemic disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), which leads to pulmonary manifestations like acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In addition, COVID-19 may cause extra-pulmonary manifestation such as testicular injury. Both high and low levels of testosterone could affect the severity of COVID-19. Herein, there is substantial controversy regarding the potential role of testosterone in SARS-CoV-2 infection and COVID-19 severity. Therefore, the present study aimed to review and elucidate the assorted view of preponderance regarding the beneficial and harmful effects of testosterone in COVID-19. A related literature search in PubMed, Scopus, Web of Science, Google Scholar, and Science Direct was done. All published articles related to the role of testosterone and COVID-19 were included in this mini-review. The beneficial effects of testosterone in COVID-19 are through inhibition of pro-inflammatory cytokines, augmentation of anti-inflammatory cytokines, modulation of the immune response, attenuation of oxidative stress, and endothelial dysfunction. However, its harmful effects in COVID-19 are due to augmentation of transmembrane protease serine 2 (TMPRSS2), which is essential for cleaving and activating SARS-CoV-2 spike protein during acute SARS-CoV-2 infection. Most published studies illustrated that low testosterone levels are linked to COVID-19 severity. A low testosterone level in COVID-19 is mainly due to testicular injury, the primary source of testosterone.

Keywords: COVID-19; TMPRSS2; anti-inflammatory cytokines; pro-inflammatory cytokines; testosterone.