Korean Circ J.  2024 Jun;54(6):295-310. 10.4070/kcj.2024.0065.

COVID-19 Vaccination-Related Myocarditis: What We Learned From Our Experience and What We Need to Do in The Future

• Park JH
• Kim KH

• KMID: 2556527
• DOI: http://doi.org/10.4070/kcj.2024.0065

Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has led to a global health crisis with substantial mortality and morbidity. To combat the COVID-19 pandemic, various vaccines have been developed, but unexpected serious adverse events including vaccine-induced thrombotic thrombocytopenia, carditis, and thromboembolic events have been reported and became a huddle for COVID-19 vaccination. Vaccine-related myocarditis (VRM) is a rare but significant adverse event associated primarily with mRNA vaccines. This review explores the incidence, risk factors, clinical presentation, pathogenesis, management strategies, and outcomes associated with VRM. The incidence of VRM is notably higher in male adolescents and young adults, especially after the second dose of mRNA vaccines. The pathogenesis appears to involve an immune-mediated process, but the precise mechanism remains mostly unknown so far. Most studies have suggested that VRM is mild and self-limiting, and responds well to conventional treatment. However, a recent nationwide study in Korea warns that severe cases, including fulminant myocarditis or death, are not uncommon in patients with COVID-19 VRM. The long-term cardiovascular consequences of VRM have not been well understood and warrant further investigation. This review also briefly addresses the critical balance between the substantial benefits of COVID-19 vaccination and the rare risks of VRM in the coming endemic era. It emphasizes the need for continued surveillance, research to understand the underlying mechanisms, and strategies to mitigate risk. Filling these knowledge gaps would be vital to refining vaccination recommendations and improving patient care in the evolving COVID-19 pandemic landscape.

Keyword

COVID-19; Vaccines; Myocarditis

Figure

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  Figure 1 Proposed pathophysiologic mechanism of coronavirus disease 2019 vaccine-related myocarditis. Vaccines for severe acute respiratory syndrome coronavirus-2 use the viral spike protein as their target. Adenoviral vaccines use a modified form of DNA adenovirus to elicit an immune response to the viral spike proteins. Upon injection, the DNA is released into the cytoplasm and later migrates into the cell nucleus without being incorporated into the cellular DNA. DNA produces mRNA that codes for viral spike proteins. In contrast, mRNA vaccines use mRNA for viral spike protein that is included in lipid nanoparticles. The mRNA then migrates back into the cytoplasm. After injection of these vaccines, the mRNA inserts itself into the cytoplasm, where it synthesizes the viral spike proteins via interaction with ribosomes. Viral spike proteins can elicit an immune response from the host’s helper T cells (CD4+ TH) and APC, resulting in the production of antibodies against viral spike proteins by B cells. Infected cells are attacked by cytotoxic T cells (CD8+ TC) coated with antibodies against viral spike proteins. It is important to note that antibodies against spike proteins may also have cross-reactivity with TNNC1 and myosin, potentially leading to an attack on the myocardium. Increased immune responses, including elevated serum concentrations of proinflammatory cytokines and chemokines, can enhance the attack. In females, sex hormones such as estrogen inhibit T cell activity and reduce the immune response. Additionally, genetic factors may contribute to the pathogenesis of myocarditis.APC = antigen-presenting cells; TC = cytotoxic T cells; TH = helper T cells; TNNC1 = cardiac troponin C1.

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