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Nat Cardiovasc Res . The cellular and molecular cardiac tissue responses in human inflammatory cardiomyopathies after SARS-CoV-2 infection and COVI

tetano

Editor, Senior Moderator
Nat Cardiovasc Res


. 2025 Feb 24.
doi: 10.1038/s44161-025-00612-6. Online ahead of print. The cellular and molecular cardiac tissue responses in human inflammatory cardiomyopathies after SARS-CoV-2 infection and COVID-19 vaccination

Henrike Maatz[SUP] #[/SUP][SUP] 1 2 [/SUP], Eric L Lindberg[SUP] #[/SUP][SUP] 3 4 [/SUP], Eleonora Adami[SUP] 3 [/SUP], Natalia López-Anguita[SUP] 3 [/SUP], Alvaro Perdomo-Sabogal[SUP] 3 [/SUP], Lucía Cocera Ortega[SUP] 3 [/SUP], Giannino Patone[SUP] 3 [/SUP], Daniel Reichart[SUP] 4 5 6 [/SUP], Anna Myronova[SUP] 3 [/SUP], Sabine Schmidt[SUP] 3 [/SUP], Ahmed Elsanhoury[SUP] 7 8 [/SUP], Oliver Klein[SUP] 7 8 [/SUP], Uwe Kühl[SUP] 7 8 [/SUP], Emanuel Wyler[SUP] 9 [/SUP], Markus Landthaler[SUP] 9 10 [/SUP], Schayan Yousefian[SUP] 9 [/SUP], Simon Haas[SUP] 9 11 12 13 [/SUP], Florian Kurth[SUP] 14 [/SUP], Sarah A Teichmann[SUP] 15 16 [/SUP], Gavin Y Oudit[SUP] 17 18 [/SUP], Hendrik Milting[SUP] 19 [/SUP], Michela Noseda[SUP] 20 21 [/SUP], Jonathan G Seidman[SUP] 5 [/SUP], Christine E Seidman[SUP] 5 6 22 [/SUP], Bettina Heidecker[SUP] 23 [/SUP], Leif E Sander[SUP] 8 14 [/SUP], Birgit Sawitzki[SUP] 24 [/SUP], Karin Klingel[SUP] 25 [/SUP], Patrick Doeblin[SUP] 7 26 [/SUP], Sebastian Kelle[SUP] 7 26 [/SUP], Sophie Van Linthout[SUP] 7 8 [/SUP], Norbert Hubner[SUP] 27 28 29 30 [/SUP], Carsten Tschöpe[SUP] 31 32 33 [/SUP]



Affiliations
Abstract

Myocarditis, characterized by inflammatory cell infiltration, can have multiple etiologies, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or, rarely, mRNA-based coronavirus disease 2019 (COVID-19) vaccination. The underlying cellular and molecular mechanisms remain poorly understood. In this study, we performed single-nucleus RNA sequencing on left ventricular endomyocardial biopsies from patients with myocarditis unrelated to COVID-19 (Non-COVID-19), after SARS-CoV-2 infection (Post-COVID-19) and after COVID-19 vaccination (Post-Vaccination). We identified distinct cytokine expression patterns, with interferon-γ playing a key role in Post-COVID-19, and upregulated IL16 and IL18 expression serving as a hallmark of Post-Vaccination myocarditis. Although myeloid responses were similar across all groups, the Post-Vaccination group showed a higher proportion of CD4[SUP]+[/SUP] T cells, and the Post-COVID-19 group exhibited an expansion of cytotoxic CD8[SUP]+[/SUP] T and natural killer cells. Endothelial cells showed gene expression changes indicative of vascular barrier dysfunction in the Post-COVID-19 group and ongoing angiogenesis across all groups. These findings highlight shared and distinct mechanisms driving myocarditis in patients with and without a history of SARS-CoV-2 infection or vaccination.


 
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