Comprehensive characterization of the transcriptional and post-transcriptional landscape in fulminant viral myocarditis

Fulminant viral myocarditis (FVM), a life-threatening cardiac inflammatory disease, contributes to a significant proportion of sudden deaths in children and young adults. However, its molecular mechanisms and the role of post-transcriptional regulation remain poorly understood. We perform RNA sequencing to comprehensively characterize the transcriptional and post-transcriptional landscape in COVID-19-induced FVM across four disease stages: healthy, post-COVID-19, FVM, and recovery. We reveal dynamic gene expression patterns related to immune activation, inflammation, and cell chemotaxis. Additionally, we identify shared and specific functional characteristics, highlighting dysregulated innate immune responses and neutrophil activation, as well as core transcription factors that coordinately regulate immune-related gene networks. Notably, we discover an FVM-specific co-expression module associated with immune dysregulation, particularly mediated by neutrophil recruitment and activation. Long non-coding RNAs (lncRNAs) may modulate neutrophil-driven inflammatory cascades. Furthermore, we uncover extensive isoform-level remodeling through alternative splicing (AS) and alternative polyadenylation (APA), which may reshape innate immune activation and inflammatory responses. This study uncovers key transcriptional and post-transcriptional mechanisms in COVID-19-induced FVM, with lncRNAs, AS, and APA events emerging as potential therapeutic targets, thereby offering new opportunities for clinical intervention and improved patient outcomes.