Abstract
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.
Keywords:
ACE2; Age; COVID-19; Heart; Sex; TMPRSS2.
Copyright © 2021 Elsevier Ltd. All rights reserved.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Aging / genetics
-
Aging / metabolism*
-
Angiotensin-Converting Enzyme 2 / biosynthesis*
-
Angiotensin-Converting Enzyme 2 / genetics
-
Animals
-
COVID-19 / epidemiology*
-
Disease Susceptibility
-
Female
-
Gene Expression Regulation, Enzymologic*
-
Heart / virology
-
Humans
-
Intestine, Small / enzymology
-
Intestine, Small / virology
-
Kidney / enzymology
-
Kidney / virology
-
Lung / enzymology
-
Lung / virology
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Middle Aged
-
Myocardium / enzymology
-
Organ Specificity
-
Receptors, Virus / biosynthesis*
-
Receptors, Virus / genetics
-
SARS-CoV-2 / physiology*
-
Serine Endopeptidases / biosynthesis
-
Serine Endopeptidases / genetics
-
Sex Characteristics*
-
Young Adult
Substances
-
Receptors, Virus
-
ACE2 protein, human
-
Ace2 protein, mouse
-
Angiotensin-Converting Enzyme 2
-
Serine Endopeptidases
-
TMPRSS2 protein, human
-
TMPRSS2 protein, mouse