
Myocarditis is a cardiac disorder with multiple etiologies characterised by inflammatory cell infiltration and can occur after SARS-CoV-2 infection or rarely following mRNA-based COVID-19 vaccination. The underlying cellular and molecular mechanisms driving these pathologies remain poorly understood. Here we performed single-nucleus-RNA-sequencing in left ventricular endomyocardial biopsies from patients with Non-COVID-19 myocarditis, following SARS-CoV-2 infection (Post-COVID-19) and COVID-19 vaccination (Post-Vaccination). We detected specific cytokine expression patterns highlighting a particular role of interferon-γ in Post-COVID-19 and upregulated IL16 and IL18 expression as a Post-Vaccination hallmark. While the myeloid response was similar between groups, CD4+T-cell proportions were higher in Post-Vaccination and cytotoxic CD8+T and NK cells expanded in Post-COVID-19. Endothelial cells showed gene expression changes suggestive of vascular barrier function deficiency in Post-COVID-19 and angiogenesis response to cardiac inflammation in all groups. Together, our results illuminate shared and distinct cellular and molecular architectures of Non-COVID-19, Post-COVID-19 and Post-Vaccination associated myocardial inflammation in human hearts.
COVID-19/immunology, SARS-CoV-2, Myocarditis/classification, Pathology, COVID-19, Single-Cell Analysis, Myocarditis/diagnosis, Single-Cell Gene Expression Analysis, SARS-CoV-2/immunology, Myocarditis/pathology
COVID-19/immunology, SARS-CoV-2, Myocarditis/classification, Pathology, COVID-19, Single-Cell Analysis, Myocarditis/diagnosis, Single-Cell Gene Expression Analysis, SARS-CoV-2/immunology, Myocarditis/pathology
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