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<p>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 <i>IL16</i> and <i>IL18</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月24日

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

摘要

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+ T cells, and the Post-COVID-19 group exhibited an expansion of cytotoxic CD8+ 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.