Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine-associated myocarditis

Rare immune-mediated cardiac tissue inflammation can occur after vaccination, including after SARS-CoV-2 mRNA vaccines, yet the underlying immune cellular and molecular mechanisms driving this pathology remain poorly understood. Here, we investigated the systemic immunopathological landscape underlying such rare cases of myopericarditis occurring after SARS-CoV-2 LNP-mRNA vaccination using peripheral blood single-cell transcriptome and repertoire sequencing, among other multimodal approaches. For single-cell sequencing, PBMCs were analyzed from a cohort of patients during acute myocarditis/pericarditis shortly after SARS-CoV-2 LNP-mRNA vaccination (n = 4), in comparison to recovered patients more than six months after vaccination (n = 3) as well as healthy vaccinated controls (n = 4).