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dc.contributor.authorBienvenu, LA
dc.contributor.authorNoonan, J
dc.contributor.authorWang, X
dc.contributor.authorPeter, K
dc.date.accessioned2020-12-16T23:52:54Z
dc.date.available2020-12-16T23:52:54Z
dc.date.issued2020-12-01
dc.identifierpii: 5924554
dc.identifier.citationBienvenu, L. A., Noonan, J., Wang, X. & Peter, K. (2020). Higher mortality of COVID-19 in males: sex differences in immune response and cardiovascular comorbidities. CARDIOVASCULAR RESEARCH, 116 (14), pp.2197-2206. https://doi.org/10.1093/cvr/cvaa284.
dc.identifier.issn0008-6363
dc.identifier.urihttp://hdl.handle.net/11343/254614
dc.description.abstractThe high mortality rate of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is a critical concern of the coronavirus disease 2019 (COVID-19) pandemic. Strikingly, men account for the majority of COVID-19 deaths, with current figures ranging from 59% to 75% of total mortality. However, despite clear implications in relation to COVID-19 mortality, most research has not considered sex as a critical factor in data analysis. Here, we highlight fundamental biological differences that exist between males and females, and how these may make significant contributions to the male-biased COVID-19 mortality. We present preclinical evidence identifying the influence of biological sex on the expression and regulation of angiotensin-converting enzyme 2 (ACE2), which is the main receptor used by SARS-CoV-2 to enter cells. However, we note that there is a lack of reports showing that sexual dimorphism of ACE2 expression exists and is of functional relevance in humans. In contrast, there is strong evidence, especially in the context of viral infections, that sexual dimorphism plays a central role in the genetic and hormonal regulation of immune responses, both of the innate and the adaptive immune system. We review evidence supporting that ineffective anti-SARS-CoV-2 responses, coupled with a predisposition for inappropriate hyperinflammatory responses, could provide a biological explanation for the male bias in COVID-19 mortality. A prominent finding in COVID-19 is the increased risk of death with pre-existing cardiovascular comorbidities, such as hypertension, obesity, and age. We contextualize how important features of sexual dimorphism and inflammation in COVID-19 may exhibit a reciprocal relationship with comorbidities, and explain their increased mortality risk. Ultimately, we demonstrate that biological sex is a fundamental variable of critical relevance to our mechanistic understanding of SARS-CoV-2 infection and the pursuit of effective COVID-19 preventative and therapeutic strategies.
dc.languageEnglish
dc.publisherOXFORD UNIV PRESS
dc.titleHigher mortality of COVID-19 in males: sex differences in immune response and cardiovascular comorbidities
dc.typeJournal Article
dc.identifier.doi10.1093/cvr/cvaa284
melbourne.affiliation.departmentMelbourne Medical School
melbourne.source.titleCardiovascular Research
melbourne.source.volume116
melbourne.source.issue14
melbourne.source.pages2197-2206
melbourne.elementsid1468854
melbourne.openaccess.urlhttps://europepmc.org/articles/PMC7665363?pdf=render
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665363
melbourne.openaccess.statusPublished version
melbourne.contributor.authorNoonan, Jonathan
melbourne.contributor.authorPeter, Karlheinz
melbourne.contributor.authorWang, Xiaowei
melbourne.contributor.authorBienvenu, Laura
dc.identifier.eissn1755-3245
melbourne.accessrightsAccess this item via the Open Access location


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