Abstract
Coronavirus disease 2019 (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 glycoprotein to the angiotensin-converting enzyme 2 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 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 or anti-androgens to mitigate COVID-19. This perspective discusses clinical and molecular advances on the rapidly evolving field of androgen receptor (AR) action on cell surface transmembrane protease serine 2 (TMPRSS2) expression and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the potential effect of anti-androgens on coronavirus disease 2019 (COVID-19) severity in male patients. It discusses limitations of current studies and offers insight for future directions.
Keywords: ACE2; COVID-19; SARS-CoV-2; TMPRSS2; androgens; sex differences; testosterone.
【저자키워드】 COVID-19, SARS-CoV-2, ACE2, Testosterone, sex differences, androgens, TMPRSS2, 【초록키워드】 coronavirus disease, severe acute respiratory syndrome coronavirus 2, Coronavirus disease 2019, coronavirus, clinical trial, therapy, severe COVID-19, Hospitalization, susceptibility, severity, spike glycoprotein, Infection, COVID-19 severity, lung, Sex, Gender, Testosterone, protease, severe acute respiratory syndrome Coronavirus, virus, angiotensin-converting enzyme 2, Spike protein, amplification, cells, male, cleavage, Prostate cancer, Androgen receptor, Anti-androgen, glycoprotein, receptor, mortality rate, women, molecular, expression, patients, Angiotensin-converting enzyme, androgens, Hypothesis, Cancer cells, angiotensin, androgen, Deprivation, followed by, acute respiratory syndrome, Activation, Recognition, Serine, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, Perspective, attachment, TMPRSS2 expression, transmembrane, limitation, viral spike, transmembrane protein, offer, anti-androgens, infect, serine 2, men, mitigate, Cell, responsible, characterized, increase, reducing, exhibiting, acting, 【제목키워드】 Therapeutics, Potential,