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Sex differences in COVID-19: candidate pathways, genetics of ACE2, and sex hormones.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2021 Jan 01; Vol. 320 (1), pp. H296-H304. Date of Electronic Publication: 2020 Dec 04. - Publication Year :
- 2021
-
Abstract
- Biological sex is increasingly recognized as a critical determinant of health and disease, particularly relevant to the topical COVID-19 pandemic caused by the SARS-CoV-2 coronavirus. Epidemiological data and observational reports from both the original SARS epidemic and the most recent COVID-19 pandemic have a common feature: males are more likely to exhibit enhanced disease severity and mortality than females. Sex differences in cardiovascular disease and COVID-19 share mechanistic foundations, namely, the involvement of both the innate immune system and the canonical renin-angiotensin system (RAS). Immunological differences suggest that females mount a rapid and aggressive innate immune response, and the attenuated antiviral response in males may confer enhanced susceptibility to severe disease. Furthermore, the angiotensin-converting enzyme 2 (ACE2) is involved in disease pathogenesis in cardiovascular disease and COVID-19, either to serve as a protective mechanism by deactivating the RAS or as the receptor for viral entry, respectively. Loss of membrane ACE2 and a corresponding increase in plasma ACE2 are associated with worsened cardiovascular disease outcomes, a mechanism attributed to a disintegrin and metalloproteinase (ADAM17). SARS-CoV-2 infection also leads to ADAM17 activation, a positive feedback cycle that exacerbates ACE2 loss. Therefore, the relationship between cardiovascular disease and COVID-19 is critically dependent on the loss of membrane ACE2 by ADAM17-mediated proteolytic cleavage. This article explores potential mechanisms involved in COVID-19 that may contribute to sex-specific susceptibility focusing on the innate immune system and the RAS, namely, genetics and sex hormones. Finally, we highlight here the added challenges of gender in the COVID-19 pandemic.
- Subjects :
- ADAM17 Protein metabolism
Adaptive Immunity genetics
Androgens metabolism
Angiotensin-Converting Enzyme 2 metabolism
COVID-19 genetics
COVID-19 metabolism
COVID-19 mortality
Cardiovascular Diseases genetics
Cardiovascular Diseases immunology
Estrogens metabolism
Female
Genes, X-Linked genetics
Genes, X-Linked immunology
Humans
Immunity, Innate genetics
Male
Promoter Regions, Genetic
Receptors, Coronavirus metabolism
Renin-Angiotensin System genetics
Renin-Angiotensin System immunology
Response Elements genetics
SARS-CoV-2 metabolism
Severity of Illness Index
Sex Characteristics
Sex Factors
X Chromosome Inactivation
Adaptive Immunity immunology
Androgens immunology
Angiotensin-Converting Enzyme 2 genetics
COVID-19 immunology
Estrogens immunology
Immunity, Innate immunology
Receptors, Coronavirus genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1539
- Volume :
- 320
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 33275517
- Full Text :
- https://doi.org/10.1152/ajpheart.00755.2020