This review highlights that pediatric viral myocarditis differs from adult disease in immune response, viral tropism, and clinical outcomes, and emphasizes the need for pediatric-specific experimental models to improve understanding and therapy development.
This review highlights the limitations of current adult murine models in studying pediatric viral myocarditis and outlines priorities for developing pediatric-specific models to advance diagnosis and targeted therapies.
Abstract Viral myocarditis is a major cause of pediatric cardiac inflammation and contributes to dilated cardiomyopathy and sudden cardiac death. Despite its impact, most mechanistic insights derive from adult models, limiting understanding of pediatric disease. This review highlights age-specific differences in immune responses, viral tropism, and clinical outcomes. We summarize the major viral pathogens associated with pediatric myocarditis and their distinct roles in acute and chronic cardiac injury. We discuss experimental infection models with attention to viral species, host strain, and route of administration, each influencing disease severity and translational relevance. Pediatric-focused models demonstrate vulnerabilities of the immune system, including limited memory responses and altered viral persistence. At the cellular and molecular level, we describe mechanisms of myocardial damage such as viral cytotoxicity, dysregulated cytokine production, maladaptive immune recruitment, and mitochondrial dysfunction. We further examine cardiomyocyte and endothelial signaling, viral evasion strategies, and the progression from acute inflammation to fibrosis and dilated cardiomyopathy. Finally, we consider anatomical and physiological differences between murine and human hearts that restrict translation and emphasize the need for pediatric-specific models to define mechanisms and guide targeted therapies. Advancing such models will be essential for reducing morbidity and mortality in affected children. Impact Provides an integrated overview of viral pathogens associated with pediatric myocarditis, emphasizing clinical presentation, molecular mechanisms, and experimental models. Clarifies how developmental differences in immune regulation and viral tropism contribute to age-specific disease outcomes. Identifies major gaps in pediatric-focused models and outlines priorities for future research needed to advance diagnosis and therapy.
Ling et al. (Fri,) conducted a review in Children with viral myocarditis including neonates and older pediatric patients with viral-induced cardiac inflammation leading to dilated cardiomyopathy or sudden cardiac death. This review highlights that pediatric viral myocarditis differs from adult disease in immune response, viral tropism, and clinical outcomes, and emphasizes the need for pediatric-specific experimental models to improve understanding and therapy development.