Article Impact Level: HIGH Data Quality: STRONG Summary of Nature Cardiovascular Research, 1–16. https://doi.org/10.1038/s44161-025-00612-6 Dr. Henrike Maatz et al.
Points
- Single-nucleus RNA sequencing was used to analyze myocarditis in 148 patients with non-COVID-19, post-COVID-19, and post-vaccination myocarditis, examining cytokine expression and immune cell profiles.
- Post-COVID-19 myocarditis was driven by interferon-γ (IFN-γ), while post-vaccination myocarditis showed increased IL16 and IL18 expression.
- CD4+ T cells were more prevalent in post-vaccination myocarditis, while CD8+ cytotoxic T cells and natural killer (NK) cells were more prominent in post-COVID-19 myocarditis.
- Endothelial dysfunction was more pronounced in post-COVID-19 myocarditis, while ongoing angiogenesis was observed across all groups, suggesting potential long-term cardiovascular effects.
- The study highlights distinct molecular mechanisms of myocarditis based on etiology, offering insights for tailored therapeutic strategies and future research on long-term cardiovascular outcomes.
Summary
This study used single-nucleus RNA sequencing to examine the cellular and molecular mechanisms underlying myocarditis in patients with varying histories of SARS-CoV-2 infection or vaccination. Left ventricular endomyocardial biopsies (EMBs) from 148 patients were analyzed, including those with non-COVID-19 myocarditis, post-COVID-19 myocarditis, and post-vaccination myocarditis. The results revealed distinct cytokine expression patterns across the groups. In patients with post-COVID-19 myocarditis, interferon-γ (IFN-γ) was a key mediator of inflammation, while post-vaccination myocarditis was characterized by increased expression of IL16 and IL18. Myeloid responses were similar across all groups, but CD4+ T cells were more prevalent in the post-vaccination group, while cytotoxic CD8+ T and natural killer (NK) cells expanded in the post-COVID-19 group.
Gene expression analysis of endothelial cells showed evidence of vascular barrier dysfunction in the post-COVID-19 group, while ongoing angiogenesis was observed across all groups. These findings underscore the shared and unique mechanisms driving myocarditis in different patient populations. Notably, endothelial dysfunction and angiogenesis were more pronounced in post-COVID-19 patients, which suggests a potential long-term impact of SARS-CoV-2 on cardiovascular health. The study highlights the importance of distinguishing the molecular characteristics of myocarditis based on etiology—whether due to viral infection or vaccination—and their distinct immunological signatures.
The findings provide important insights into the immune response in myocarditis following SARS-CoV-2 infection and vaccination, with implications for clinical management and future therapeutic strategies. By identifying the key cytokines and immune cell profiles involved in these distinct forms of myocarditis, this study offers potential targets for intervention. Further research is needed to explore the long-term cardiovascular effects of these inflammatory processes, particularly in patients with ongoing symptoms or those at higher risk for severe complications.
Link to the article: https://www.nature.com/articles/s44161-025-00612-6
References Maatz, H., Lindberg, E. L., Adami, E., López-Anguita, N., Perdomo-Sabogal, A., Cocera Ortega, L., Patone, G., Reichart, D., Myronova, A., Schmidt, S., Elsanhoury, A., Klein, O., Kühl, U., Wyler, E., Landthaler, M., Yousefian, S., Haas, S., Kurth, F., Teichmann, S. A., … Tschöpe, C. (2025). The cellular and molecular cardiac tissue responses in human inflammatory cardiomyopathies after SARS-CoV-2 infection and COVID-19 vaccination. Nature Cardiovascular Research, 1–16. https://doi.org/10.1038/s44161-025-00612-6
