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Endocrinology ; 162(8)2021 08 01.
Article in English | MEDLINE | ID: covidwho-1259229

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.


Subject(s)
Androgen Antagonists/therapeutic use , COVID-19/drug therapy , SARS-CoV-2 , Animals , Gene Expression/drug effects , Humans , Lung/metabolism , Lung/virology , Male , Mice , Prostatic Neoplasms/drug therapy , Receptors, Androgen/drug effects , Receptors, Androgen/physiology , SARS-CoV-2/physiology , Serine Endopeptidases/drug effects , Serine Endopeptidases/genetics , Serine Endopeptidases/physiology , Sex Factors
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