Sex- and age-specific regulation of ACE2: Insights into severe COVID-19 susceptibility

Aged males disproportionately succumb to increased COVID-19 severity, hospitalization, and mortality compared to females. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2) facilitate SARS-CoV-2 viral entry and may have sexually dimorphic regulation. As viral load dictates disease severity, we investigated the expression, protein levels, and activity of ACE2 and TMPRSS2. Our data reveal that aged males have elevated ACE2 in both mice and humans across organs. We report the first comparative study comprehensively investigating the impact of sex and age in murine and human levels of ACE2 and TMPRSS2, to begin to elucidate the sex bias in COVID-19 severity.

Automated summary

Research indicates that aged males are more susceptible to the impacts of COVID-19 compared to females, possibly due to higher levels of ACE2 in their bodies. The study aims to begin elucidating the gender bias in the severity of COVID-19 by investigating the expression and activity of ACE2 and TMPRSS2 in mice and humans of different ages and sexes.