“Bridging the clinical, molecular and genetic perspectives on myocarditis in post-COVID-19 era”

Myocarditis is a non-familial inflammatory manifestation of the myocardium, primarily induced by viral infections, but it may also stem from bacterial pathogens, autoimmune disorders, or adverse drug reactions. Its diagnosis remains challenging due to heterogeneous and often non-specific clinical presentations. Recent epidemiological studies have indicated a markedly increased incidence of myocarditis following SARS-CoV-2 infection and mRNA COVID-19 vaccinations (to a lesser extent) compared to pre-pandemic statistics. While a significant number of cases follow a mild and self-limiting disease course, severe manifestations can lead to arrhythmias, heart failure, or even sudden cardiac death. Importantly, accumulating evidence indicates that even mild myocarditis confers an elevated long-term risk of adverse cardiovascular outcomes. Beyond clinical and imaging-based observations, recent advances highlight a critical role for host genetic susceptibility in modulating immune responses, myocardial injury, and disease severity. This review provides a comprehensive synthesis of the etiology, pathophysiological mechanisms, clinical spectrum, diagnostic approaches, and evidence-based management of COVID-19-associated myocarditis, while critically integrating emerging genetic and transcriptomic insights that may explain disease heterogeneity, variable inter-individual susceptibility, and long-term prognosis. By bridging clinical aspects with molecular and genetic frameworks, this review underscores the importance of personalized risk stratification, vigilant post-recovery surveillance, and targeted preventive strategies in the post-pandemic era.