Sex differences in COVID-19: candidate pathways, genetics of ACE2, and sex hormones.
Am J Physiol Heart Circ Physiol
; 320(1): H296-H304, 2021 01 01.
Article
in English
| MEDLINE | ID: covidwho-961166
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Estrogens
/
Adaptive Immunity
/
Receptors, Coronavirus
/
Angiotensin-Converting Enzyme 2
/
COVID-19
/
Immunity, Innate
/
Androgens
Type of study:
Observational study
/
Prognostic study
Limits:
Female
/
Humans
/
Male
Language:
English
Journal:
Am J Physiol Heart Circ Physiol
Journal subject:
Cardiology
/
Physiology
Year:
2021
Document Type:
Article
Affiliation country:
Ajpheart.00755.2020
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