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Open AccessCommentary

Sex-Specific SARS-CoV-2 Mortality: Among Hormone-Modulated ACE2 Expression, Risk of Venous Thromboembolism and Hypovitaminosis D

1
Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
2
Department of Experimental and Clinical Medicine, Magna Graecia University Catanzaro, 88100 Catanzaro, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(8), 2948; https://doi.org/10.3390/ijms21082948
Received: 3 April 2020 / Revised: 15 April 2020 / Accepted: 21 April 2020 / Published: 22 April 2020
(This article belongs to the Section Molecular Endocrinology and Metabolism)
Severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease (COVID-19) appears to have a higher mortality rate in presence of comorbidities and in men. The latter suggests the presence of a possible sex-dependent susceptibility. An enzymatic system involved in this different predisposition could be represented by angiotensin converting enzyme 2 (ACE2). ACE2 is activated and down-regulated by the spike protein of the virus and allows the penetration of SARS-CoV-2 into epithelial cells and myocardium. Data on the experimental animal have shown that 17ß-estradiol increases the expression and activity of ACE2 in both adipose tissue and kidney. Spontaneously hypertensive male mice have a higher myocardial ACE2 expression than females and its levels decrease after orchiectomy. In addition to this first aspect, the recent evidence of an increased frequency of venous thromboembolism in patients with COVID-19 (a clinical element associated with a worse prognosis) calls the attention on the safety of treatment with testosterone, in particular in hypogonadal men with greater genetic predisposition. Evidence that sex hormones are able to modulate the expression of ACE2 could help in interpreting epidemiological results and in designing more appropriate intervention strategies. Moreover, the vitamin D deficiency in elderly men may be worthy of further study regarding the epidemiological aspects of this different susceptibility and lethality between sexes.
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Keywords: SARS-CoV2; COVID-19; ACE2: venous thromboembolism; vitamin D deficiency; gender differences SARS-CoV2; COVID-19; ACE2: venous thromboembolism; vitamin D deficiency; gender differences
MDPI and ACS Style

La Vignera, S.; Cannarella, R.; Condorelli, R.A.; Torre, F.; Aversa, A.; Calogero, A.E. Sex-Specific SARS-CoV-2 Mortality: Among Hormone-Modulated ACE2 Expression, Risk of Venous Thromboembolism and Hypovitaminosis D. Int. J. Mol. Sci. 2020, 21, 2948.

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