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

Abstract

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 immune responses and cardiotoxicity.

Immune Response in Regard to Hypersensitivity Reactions after COVID-19 Vaccination

“…The test results revealed markedly increased IL-18, IL-27, and Th1-type cytokine levels and activated circulating NK cells and T-cells. The monocytes also expressed increased levels of IL-18 and the NLRP3 inflammasome, similar to findings observed in mice with cardiac dysfunction following the administration of recombinant-IL18 [67].…”

New-onset dermatomyositis following SARS-CoV-2 infection and vaccination: a case-based review

“…NLRP3 inflammasome activation has also been detected in myocarditis after mRNA vaccination. It is assumed, that similarly to SARS-CoV-2 infection, spike protein might trigger NLRP3 inflammasome activity, or that the lipid nanoparticles used, might stimulate the NLRP3 inflammasome [ 50 , 51 ]. This might present another additional pathomechanism in the development of autoimmune diseases like dermatomyositis following mRNA vaccination.…”

IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohort

“…IL-27 also has potent antiviral effects against influenza, hepatitis B and C viruses, human immunodeficiency virus and others, by stimulating IFNγ production by CD8+ T cells and modulating innate responses ( 46 ). Marked elevation of IL-27 was reported in a single case of mRNA-1273 COVID-19 vaccine-related myocarditis, with more moderate increases in IL-27 in recently vaccinated control individuals (incidentally, inflammasome activation was also implicated in the vaccine-related myocarditis) ( 47 ). Indeed, IL-27 production by B cells has been shown to contribute to cytotoxic CD8 T cell responses to SARS-CoV-2 subunit vaccines, suggesting the importance of this cytokine in the viral response to SARS-CoV-2 ( 48 , 49 ).…”