The cellular and molecular cardiac tissue responses in human inflammatory cardiomyopathies after SARS-CoV-2 infection and COVID-19 vaccination
Maatz, Henrike; Lindberg, Eric L.; Adami, Eleonora; López-Anguita, Natalia; Perdomo-Sabogal, Alvaro; Cocera Ortega, Lucía; Patone, Giannino; Reichart, Daniel; Myronova, Anna; Schmidt, Sabine; Elsanhoury, Ahmed; Klein, Oliver; Kühl, Uwe; Wyler, Emanuel; Landthaler, Markus; Yousefian, Schayan; Haas, Simon; Kurth, Florian; Teichmann, Sarah A.; Oudit, Gavin Y.; Milting, Hendrik; Noseda, Michela; Seidman, Jonathan G.; Seidman, Christine E.; Heidecker, Bettina; Sander, Leif E.; Sawitzki, Birgit; Klingel, Karin; Doeblin, Patrick; Kelle, Sebastian; Van Linthout, Sophie; Hubner, Norbert; Tschöpe, Carsten
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.
Link | PDF (Nature Cardiovascular Research) [Open Access]
Maatz, Henrike; Lindberg, Eric L.; Adami, Eleonora; López-Anguita, Natalia; Perdomo-Sabogal, Alvaro; Cocera Ortega, Lucía; Patone, Giannino; Reichart, Daniel; Myronova, Anna; Schmidt, Sabine; Elsanhoury, Ahmed; Klein, Oliver; Kühl, Uwe; Wyler, Emanuel; Landthaler, Markus; Yousefian, Schayan; Haas, Simon; Kurth, Florian; Teichmann, Sarah A.; Oudit, Gavin Y.; Milting, Hendrik; Noseda, Michela; Seidman, Jonathan G.; Seidman, Christine E.; Heidecker, Bettina; Sander, Leif E.; Sawitzki, Birgit; Klingel, Karin; Doeblin, Patrick; Kelle, Sebastian; Van Linthout, Sophie; Hubner, Norbert; Tschöpe, Carsten
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.
Link | PDF (Nature Cardiovascular Research) [Open Access]
