Increased Interleukin 18-Dependent Immune Responses Are Associated With Myopericarditis After COVID-19 mRNA Vaccination

作者：Taejoon Won, Nisha A. Gilotra, Megan Kay Wood, David Matthew Hughes, Monica V. Talor, Jana Lovell, Aaron M. Milstone, Charles Steenbergen, Daniela Čiháková · 发表于：Frontiers in Immunology · 年份：2022 · DOI：10.3389/fimmu.2022.851620 · 被引用次数：50 · 研究领域：Viral Infections and Immunology Research、Inflammasome and immune disorders、SARS-CoV-2 and COVID-19 Research

Myocarditis and myopericarditis may occur after COVID-19 vaccination with an incidence of two to twenty cases per 100,000 individuals, but underlying mechanisms related to disease onset and progression remain unclear. Here, we report a case of myopericarditis following the first dose of the mRNA-1273 COVID-19 vaccine in a young man who had a history of mild COVID-19 three months before vaccination. The patient presented with chest pain, elevated troponin I level, and electrocardiogram abnormality. His endomyocardial biopsy revealed diffuse CD68 + cell infiltration. We characterized the immune profile of the patient using multiplex cytokine assay and flow cytometry analysis. Sex-matched vaccinated individuals and healthy individuals were used as controls. IL-18 and IL-27, Th1-type cytokines, were highly increased in the patient with COVID-19 vaccine-related myopericarditis compared with vaccinated controls who experienced no cardiac complications. In the patient, circulating NK cells and T cells showed an activated phenotype and mRNA profile, and monocytes expressed increased levels of IL-18 and its upstream NLRP3 inflammasome. We found that recombinant IL-18 administration into mice caused mild cardiac dysfunction and activation of NK cells and T cells in the hearts, similar to the findings in the patient with myopericarditis after COVID-19 mRNA vaccination. Collectively, myopericarditis following COVID-19 mRNA vaccination may be associated with increased IL-18-mediated immun...