To The Editor:
We thank Gersh and colleagues1 for their letter in response to our article "Sex-Biased Vulnerability of the Heart to COVID-19.”2 In fact, we are pleased to see that our article is fulfilling its purpose of drawing attention to a topic little explored, putting forward notions and hypotheses for the field to contemplate.
We agree with Gersh and colleagues regarding the importance and relevance of the role of sex hormones beyond the reproductive system, particularly in the cardiovascular system as we have shown previously.3 , 4 Given the importance of angiotensin-converting enzyme 2 in severe acute respiratory syndrome coronavirus 2 host cell entry, Gersh and colleagues accurately point out the influence of estradiol on the renin-angiotensin-aldosterone system (RAAS). In this context, we have recently discussed the modulatory actions of estradiol on RAAS in detail, thereby impacting several components of the cardiovascular system.5 , 6
The purpose of our article was to postulate on the role of biological sex and the potential mechanisms that could increase risk of cardiac complications more in male than female coronavirus disease 2019 (COVID-19) patients, thereby providing a hypothesis on the molecular factors related to the cardiovascular system that may contribute to the observed sex-biased crude fatality rates. At the same time, the importance of the potential impact of sex hormones on COVID-19–induced cardiovascular complications has been recently discussed in Mayo Clinic Proceedings.7
Therefore, we concur with Gersh and colleagues, and we consider their comments insightful, contributing to awareness of the role of biological sex and the regulatory effects of sex hormones on (patho)physiological mechanisms.
Footnotes
Potential Competing Interests: The authors report no potential competing interests.
References
- 1.Gersh F.L., O'Keefe J.H., Henry B.M. COVID-19, the female immune advantage, and cardiovascular impact. Mayo Clin Proc. 2021;96(3):818–819. doi: 10.1016/j.mayocp.2020.12.021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Ritter O., Kararigas G. Sex-biased vulnerability of the heart to COVID-19. Mayo Clin Proc. 2020;95(11):2332–2335. doi: 10.1016/j.mayocp.2020.09.017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Kararigas G., Bito V., Tinel H. Transcriptome characterization of estrogen-treated human myocardium identifies Myosin regulatory light chain interacting protein as a sex-specific element influencing contractile function. J Am Coll Cardiol. 2012;59(4):410–417. doi: 10.1016/j.jacc.2011.09.054. [DOI] [PubMed] [Google Scholar]
- 4.Kararigas G., Nguyen B.T., Zelarayan L.C. Genetic background defines the regulation of postnatal cardiac growth by 17beta-estradiol through a beta-catenin mechanism. Endocrinology. 2014;155(7):2667–2676. doi: 10.1210/en.2013-2180. [DOI] [PubMed] [Google Scholar]
- 5.Sabbatini A.R., Kararigas G. Estrogen-related mechanisms in sex differences of hypertension and target organ damage. Biol Sex Differ. 2020;11(1):31. doi: 10.1186/s13293-020-00306-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Sabbatini A.R., Kararigas G. Menopause-related estrogen decrease and the pathogenesis of HFpEF: JACC review topic of the week. J Am Coll Cardiol. 2020;75(9):1074–1082. doi: 10.1016/j.jacc.2019.12.049. [DOI] [PubMed] [Google Scholar]
- 7.Al-Lami R.A., Urban R.J., Volpi E., Algburi A.M.A., Baillargeon J. Sex hormones and novel corona virus infectious disease (COVID-19) Mayo Clin Proc. 2020;95(8):1710–1714. doi: 10.1016/j.mayocp.2020.05.013. [DOI] [PMC free article] [PubMed] [Google Scholar]