The cellular and molecular cardiac tissue responses in human inflammatory cardiomyopathies after SARS-CoV-2 infection and COVID-19 vaccination

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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Publication Details

Journal
Nature Cardiovascular Research
Published
2025-02-24
DOI
https://doi.org/10.1038/s44161-025-00612-6
Citations
14
Primary Topic
Viral Infections and Immunology Research
Type
article
Field-Weighted Citation Impact
19.43
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article

The cellular and molecular cardiac tissue responses in human inflammatory cardiomyopathies after SARS-CoV-2 infection and COVID-19 vaccination

Sabine Schmidt, Uwe Kühl, Christine E. Seidman, Bettina Heidecker et al.
14 citations
Nature Cardiovascular Research
Viral Infections and Immunology Research
19.43
article

The cellular and molecular cardiac tissue responses in human inflammatory cardiomyopathies after SARS-CoV-2 infection and COVID-19 vaccination

Sabine Schmidt, Uwe Kühl, Christine E. Seidman, Bettina Heidecker, Gavin Y. Oudit, Birgit Sawitzki, Jonathan G. Seidman, Schayan Yousefian, Sarah Amalia Teichmann, Simon Haas, Sophie Van Linthout, Ahmed Elsanhoury, Oliver Klein, Leif Erik Sander, Lucía Ortega, Eric L. Lindberg, Karin Klingel, Michela Noseda, Henrike Maatz, Anna Myronova, Markus Landthaler, Hendrik Milting, Norbert Hübner, Eleonora Adami, Patrick Doeblin, Sebastian Kelle, Florian Kurth, Emanuel Wyler, Giannino Patone, Álvaro Perdomo-Sabogal, Natalia López-Anguita, Daniel Reichart, Carsten Tschöpe
article en
14 citations

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.

Nature Cardiovascular ResearchVol. 4(3)
Brigham and Women's Hospital (US), Helmholtz Association of German Research Centres (DE), Howard Hughes Medical Institute (US), Harvard University (US), University of Alberta (CA), Max Delbrück Center (DE), Heidelberg University (DE), University of Cambridge (GB), Heart and Diabetes Center North Rhine-Westphalia (DE), Wellcome Sanger Institute (GB), LMU Klinikum (DE), British Heart Foundation (GB), Humboldt-Universität zu Berlin (DE), German Cancer Society (DE), Deutsches Herzzentrum der Charité (DE), German Centre for Cardiovascular Research (DE), Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE), Imperial College London (GB), Freie Universität Berlin (DE), Charité - Universitätsmedizin Berlin (DE), Ludwig-Maximilians-Universität München (DE), Heidelberg University (US), Ruhr University Bochum (DE)
Good health and well-being
Openalex Percentile: Top 1%
Viral Infections and Immunology Research
19.43
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