Sex Hormones in COVID-19 Severity: The Quest for Evidence and Influence Mechanisms

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2024 Jun 26

PMID 38923119

Authors

Haiqing Xiao

Jiayi Wei

Lunzhi Yuan

Jiayuan Li

Chang Zhang

Gang Liu

Xuan Liu

Affiliations

Soon will be listed here.

Abstract

Studies have reported variable effects of sex hormones on serious diseases. Severe disease and mortality rates in COVID-19 show marked gender differences that may be related to sex hormones. Sex hormones regulate the expression of the viral receptors ACE2 and TMPRSS2, which affect the extent of viral infection and consequently cause variable outcomes. In addition, sex hormones have complex regulatory mechanisms that affect the immune response to viruses. These hormones also affect metabolism, leading to visceral obesity and severe disease can result from complications such as thrombosis. This review presents the latest researches on the regulatory functions of hormones in viral receptors, immune responses, complications as well as their role in COVID-19 progression. It also discusses the therapeutic possibilities of these hormones by reviewing the recent findings of clinical and assay studies.

References

Ackermann M, Verleden S, Kuehnel M, Haverich A, Welte T, Laenger F . Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 2020; 383(2):120-128. PMC: 7412750. DOI: 10.1056/NEJMoa2015432. View

Maenosono R, Nian Y, Iske J, Liu Y, Minami K, Rommel T . Recipient sex and estradiol levels affect transplant outcomes in an age-specific fashion. Am J Transplant. 2021; 21(10):3239-3255. PMC: 8924905. DOI: 10.1111/ajt.16611. View

Breslin N, Baptiste C, Miller R, Fuchs K, Goffman D, Gyamfi-Bannerman C . Coronavirus disease 2019 in pregnancy: early lessons. Am J Obstet Gynecol MFM. 2020; 2(2):100111. PMC: 7271091. DOI: 10.1016/j.ajogmf.2020.100111. View

Infante M, Pieri M, Lupisella S, DAmore L, Bernardini S, Fabbri A . Low testosterone levels and high estradiol to testosterone ratio are associated with hyperinflammatory state and mortality in hospitalized men with COVID-19. Eur Rev Med Pharmacol Sci. 2021; 25(19):5889-5903. DOI: 10.26355/eurrev_202110_26865. View

Lemes R, Costa A, Bartolomeo C, Bassani T, Nishino M, da Silva Pereira G . 17β-estradiol reduces SARS-CoV-2 infection in vitro. Physiol Rep. 2021; 9(2):e14707. PMC: 7814496. DOI: 10.14814/phy2.14707. View

Tukiainen T, Villani A, Yen A, Rivas M, Marshall J, Satija R . Landscape of X chromosome inactivation across human tissues. Nature. 2017; 550(7675):244-248. PMC: 5685192. DOI: 10.1038/nature24265. View

Lovejoy J, Bray G, Bourgeois M, Macchiavelli R, Rood J, Greeson C . Exogenous androgens influence body composition and regional body fat distribution in obese postmenopausal women--a clinical research center study. J Clin Endocrinol Metab. 1996; 81(6):2198-203. DOI: 10.1210/jcem.81.6.8964851. View

Aguilar-Pineda J, Albaghdadi M, Jiang W, Vera-Lopez K, Nieto-Montesinos R, Alvarez K . Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry. Int J Mol Sci. 2021; 22(21). PMC: 8584232. DOI: 10.3390/ijms222111508. View

Hale S, Birnbaum Y, Kloner R . beta-Estradiol, but not alpha-estradiol, reduced myocardial necrosis in rabbits after ischemia and reperfusion. Am Heart J. 1996; 132(2 Pt 1):258-62. DOI: 10.1016/s0002-8703(96)90419-6. View

10.

Welen K, Rosendal E, Gisslen M, Lenman A, Freyhult E, Fonseca-Rodriguez O . A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome: No Evidence of Benefit, Supported by Epidemiology and In Vitro Data. Eur Urol. 2022; 81(3):285-293. PMC: 8673828. DOI: 10.1016/j.eururo.2021.12.013. View

11.

Wu Y, Guo C, Tang L, Hong Z, Zhou J, Dong X . Prolonged presence of SARS-CoV-2 viral RNA in faecal samples. Lancet Gastroenterol Hepatol. 2020; 5(5):434-435. PMC: 7158584. DOI: 10.1016/S2468-1253(20)30083-2. View

12.

Keidar S, Gamliel-Lazarovich A, Kaplan M, Pavlotzky E, Hamoud S, Hayek T . Mineralocorticoid receptor blocker increases angiotensin-converting enzyme 2 activity in congestive heart failure patients. Circ Res. 2005; 97(9):946-53. DOI: 10.1161/01.RES.0000187500.24964.7A. View

13.

Li C, Li C, Lin Y, Ho M, Chen D, Chen P . Androgen Receptor Enhances Hepatic Telomerase Reverse Transcriptase Gene Transcription After Hepatitis B Virus Integration or Point Mutation in Promoter Region. Hepatology. 2018; 69(2):498-512. DOI: 10.1002/hep.30201. View

14.

Kassir R . Risk of COVID-19 for patients with obesity. Obes Rev. 2020; 21(6):e13034. PMC: 7235532. DOI: 10.1111/obr.13034. View

15.

Yeap B, Marriott R, Manning L, Dwivedi G, Hankey G, Wu F . Higher premorbid serum testosterone predicts COVID-19-related mortality risk in men. Eur J Endocrinol. 2022; 187(1):159-170. PMC: 9175556. DOI: 10.1530/EJE-22-0104. View

16.

Schroeder M, Schaumburg B, Mueller Z, Parplys A, Jarczak D, Roedl K . High estradiol and low testosterone levels are associated with critical illness in male but not in female COVID-19 patients: a retrospective cohort study. Emerg Microbes Infect. 2021; 10(1):1807-1818. PMC: 8451658. DOI: 10.1080/22221751.2021.1969869. View

17.

Heine P, Taylor J, Iwamoto G, Lubahn D, Cooke P . Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. Proc Natl Acad Sci U S A. 2000; 97(23):12729-34. PMC: 18832. DOI: 10.1073/pnas.97.23.12729. View

18.

Song H, Seddighzadeh B, Cooperberg M, Huang F . Expression of ACE2, the SARS-CoV-2 Receptor, and TMPRSS2 in Prostate Epithelial Cells. Eur Urol. 2020; 78(2):296-298. PMC: 7200365. DOI: 10.1016/j.eururo.2020.04.065. View

19.

Seillet C, Laffont S, Tremollieres F, Rouquie N, Ribot C, Arnal J . The TLR-mediated response of plasmacytoid dendritic cells is positively regulated by estradiol in vivo through cell-intrinsic estrogen receptor α signaling. Blood. 2011; 119(2):454-64. DOI: 10.1182/blood-2011-08-371831. View

20.

Nickols N, Mi Z, DeMatt E, Biswas K, Clise C, Huggins J . Effect of Androgen Suppression on Clinical Outcomes in Hospitalized Men With COVID-19: The HITCH Randomized Clinical Trial. JAMA Netw Open. 2022; 5(4):e227852. PMC: 9020208. DOI: 10.1001/jamanetworkopen.2022.7852. View