Sex Differences in Coronavirus Disease 2019 Myocarditis

Overview

Journal Curr Opin Physiol

Date 2023 Sep 4

PMID 37662585

Authors

Danielle J Beetler

DeLisa Fairweather

Affiliations

Soon will be listed here.

Abstract

Myocarditis is frequently caused by viral infections, but animal models that closely resemble human disease suggest that virus-triggered autoimmune disease is the most likely cause of myocarditis. Myocarditis is a rare condition that occurs primarily in men under age 50. The incidence of myocarditis rose at least 15x during the COVID-19 pandemic from 1-10 to 150-400 cases/100,000 individuals, with most cases occurring in men under age 50. COVID-19 vaccination was also associated with rare cases of myocarditis primarily in young men under 50 years of age with an incidence as high as 50 cases/100,000 individuals reported for some mRNA vaccines. Sex differences in the immune response to COVID-19 are virtually identical to the mechanisms known to drive sex differences in myocarditis pre-COVID based on clinical studies and animal models. The many similarities between COVID-19 vaccine-associated myocarditis to COVID-19 myocarditis and non-COVID myocarditis suggest common immune mechanisms drive disease.

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References

Toldo S, Bussani R, Nuzzi V, Bonaventura A, Mauro A, Cannata A . Inflammasome formation in the lungs of patients with fatal COVID-19. Inflamm Res. 2020; 70(1):7-10. PMC: 7572246. DOI: 10.1007/s00011-020-01413-2. View

Gu H, Chen Q, Yang G, He L, Fan H, Deng Y . Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy. Science. 2020; 369(6511):1603-1607. PMC: 7574913. DOI: 10.1126/science.abc4730. View

Chappell M . Renin-Angiotensin System and Sex Differences in COVID-19: A Critical Assessment. Circ Res. 2023; 132(10):1320-1337. PMC: 10171311. DOI: 10.1161/CIRCRESAHA.123.321883. View

Song X, Hu W, Yu H, Zhao L, Zhao Y, Zhao X . Little to no expression of angiotensin-converting enzyme-2 on most human peripheral blood immune cells but highly expressed on tissue macrophages. Cytometry A. 2020; 103(2):136-145. DOI: 10.1002/cyto.a.24285. View

Fairweather D, Beetler D, Di Florio D, Musigk N, Heidecker B, Cooper Jr L . COVID-19, Myocarditis and Pericarditis. Circ Res. 2023; 132(10):1302-1319. PMC: 10171304. DOI: 10.1161/CIRCRESAHA.123.321878. View

Huber S, Massri M, Grasse M, Fleischer V, Kellnerova S, Harpf V . Systemic Inflammation and Complement Activation Parameters Predict Clinical Outcome of Severe SARS-CoV-2 Infections. Viruses. 2021; 13(12). PMC: 8707937. DOI: 10.3390/v13122376. View

Myers J, Fairweather D, Huber S, Cunningham M . Autoimmune myocarditis, valvulitis, and cardiomyopathy. Curr Protoc Immunol. 2013; Chapter 15:Unit 15.14.1-51. PMC: 3672855. DOI: 10.1002/0471142735.im1514s101. View

Green M, Nitzan D, Schwartz N, Niv Y, Peer V . Sex differences in the case-fatality rates for COVID-19-A comparison of the age-related differences and consistency over seven countries. PLoS One. 2021; 16(4):e0250523. PMC: 8084161. DOI: 10.1371/journal.pone.0250523. View

Yuan S, Ye Z, Liang R, Tang K, Zhang A, Lu G . Pathogenicity, transmissibility, and fitness of SARS-CoV-2 Omicron in Syrian hamsters. Science. 2022; 377(6604):428-433. DOI: 10.1126/science.abn8939. View

10.

Davis M, Bobba A, Chourasia P, Gangu K, Shuja H, Dandachi D . COVID-19 Associated Myocarditis Clinical Outcomes among Hospitalized Patients in the United States: A Propensity Matched Analysis of National Inpatient Sample. Viruses. 2022; 14(12). PMC: 9785561. DOI: 10.3390/v14122791. View

11.

Chen L, Li X, Chen M, Feng Y, Xiong C . The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res. 2020; 116(6):1097-1100. PMC: 7184507. DOI: 10.1093/cvr/cvaa078. View

12.

Galasso V, Pons V, Profeta P, Becher M, Brouard S, Foucault M . Gender differences in COVID-19 attitudes and behavior: Panel evidence from eight countries. Proc Natl Acad Sci U S A. 2020; 117(44):27285-27291. PMC: 7959517. DOI: 10.1073/pnas.2012520117. View

13.

cihakova D, Sharma R, Fairweather D, Afanasyeva M, Rose N . Animal models for autoimmune myocarditis and autoimmune thyroiditis. Methods Mol Med. 2004; 102:175-93. DOI: 10.1385/1-59259-805-6:175. View

14.

Patel N, Sethi Y, Kaka N, Kaiwan O, Gupta I, Shaheen R . Acute Hepatitis of Unknown Origin in Pediatric Age Group: Recent Outbreaks and Approach to Management. J Clin Med. 2023; 12(1). PMC: 9821143. DOI: 10.3390/jcm12010009. View

15.

Frisancho-Kiss S, Davis S, Nyland J, Frisancho J, cihakova D, Barrett M . Cutting edge: cross-regulation by TLR4 and T cell Ig mucin-3 determines sex differences in inflammatory heart disease. J Immunol. 2007; 178(11):6710-4. DOI: 10.4049/jimmunol.178.11.6710. View

16.

Vahidy F, Pan A, Ahnstedt H, Munshi Y, Choi H, Tiruneh Y . Sex differences in susceptibility, severity, and outcomes of coronavirus disease 2019: Cross-sectional analysis from a diverse US metropolitan area. PLoS One. 2021; 16(1):e0245556. PMC: 7806140. DOI: 10.1371/journal.pone.0245556. View

17.

Heidecker B . Rediscovery of magnetocardiography for diagnostic screening and monitoring of treatment response in cardiology. Eur Heart J. 2023; 44(24):2140-2142. PMC: 10290870. DOI: 10.1093/eurheartj/ehad213. View

18.

Eriksson U, Kurrer M, Sonderegger I, Iezzi G, Tafuri A, Hunziker L . Activation of dendritic cells through the interleukin 1 receptor 1 is critical for the induction of autoimmune myocarditis. J Exp Med. 2003; 197(3):323-31. PMC: 2193833. DOI: 10.1084/jem.20021788. View

19.

Amin S, Aktar S, Rahman M, Chowdhury M . NLRP3 inflammasome activation in COVID-19: an interlink between risk factors and disease severity. Microbes Infect. 2021; 24(1):104913. PMC: 8613976. DOI: 10.1016/j.micinf.2021.104913. View

20.

Ozieranski K, Tyminska A, Kruk M, Kon B, Skwarek A, Opolski G . Occurrence, Trends, Management and Outcomes of Patients Hospitalized with Clinically Suspected Myocarditis-Ten-Year Perspectives from the MYO-PL Nationwide Database. J Clin Med. 2021; 10(20). PMC: 8539273. DOI: 10.3390/jcm10204672. View