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Sex differences in COVID-19: candidate pathways, genetics of ACE2, and sex hormones.
Viveiros, Anissa; Rasmuson, Jaslyn; Vu, Jennie; Mulvagh, Sharon L; Yip, Cindy Y Y; Norris, Colleen M; Oudit, Gavin Y.
  • Viveiros A; Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
  • Rasmuson J; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada.
  • Vu J; Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
  • Mulvagh SL; Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
  • Yip CYY; Division of Cardiology, Dalhousie University, Halifax, Canada.
  • Norris CM; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.
  • Oudit GY; Heart and Stroke Foundation of Canada, Toronto, Canada.
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.
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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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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