Mechanistic insights into COVID-19 mRNA vaccine-associated myocarditis: a bioinformatics analysis.

PURPOSE

While COVID-19 vaccination offers significant public health benefits, it also has potential risks, such as myocarditis. The mechanisms underlying myocarditis after COVID-19 vaccination remain poorly understood. The purpose of this study was to identify potential pathogenic genes and molecular pathways related with COVID-19 mRNA vaccine-associated myocarditis.

METHODS

Differentially expressed genes (DEGs) were analyzed from a fulminant myocarditis (FM) cohort and a COVID-19 mRNA vaccination dataset. Shared DEGs were intersected, followed by functional enrichment, protein-protein interaction (PPI) network construction, and hub gene identification. Transcriptional and miRNA regulatory networks, as well as therapeutic drug predictions were also performed.

RESULTS

Eighty shared DEGs were identified by interacting DEGs from the FM cohort and the vaccination cohort, we identified. Functional enrichment analysis revealed that DEGs are significantly involved in immune cell-mediated responses, highlighting the critical role of immune dysregulation. PPI network analysis revealed three hub genes (CXCR3, NKG7, and GZMH), which may be involved in the pathogenesis of vaccine-associated myocarditis. Furthermore, transcriptional networks highlighted TBX21 and STAT4 as key regulators of all hub genes, while hsa-mir-146a-5p targeted CXCR3 and NKG7. PhIP, a compound targeting CXCR3 and NKG7, emerged as a potential therapeutic candidate.

CONCLUSION

This study implicates immune dysregulation driven by CXCR3, NKG7, and GZMH in post-vaccination myocarditis, supported by regulatory networks and therapeutic insights using a bioinformatics analysis. These findings advance mechanistic understanding of this rare adverse event and propose potential treatment strategy for further investigation.