Cardiac Manifestations and Emerging Biomarkers in Multisystem Inflammatory Syndrome in Children (MIS-C): A Systematic Review and Meta-Analysis.

BACKGROUND

Cardiac involvement is a key prognostic factor in multisystem inflammatory syndrome in children (MIS-C), a rare but serious inflammatory condition that typically occurs 2-6 weeks after SARS-CoV-2 infection and is characterized by fever, systemic inflammation, and multiorgan involvement. Biomarkers may aid in early detection, severity assessment, and treatment stratification.

OBJECTIVE

To evaluate the diagnostic utility of established and emerging serum biomarkers in MIS-C, with an emphasis on cardiac dysfunction and disease severity.

METHODS

A systematic search was conducted in PubMed, Scopus, and Web of Science up to April 2025. Eligible studies included pediatric MIS-C cases with reported serum biomarkers. Meta-analyses were performed for NT-proBNP and troponin using random-effects models. Descriptive profiling was applied to emerging biomarkers. Subgroup comparisons were explored between severe and moderate MIS-C. Quality assessment followed the Newcastle-Ottawa Scale, and publication bias was assessed via funnel plots and Egger's test.

RESULTS

A total of 67 studies were included, comprising >4000 pediatric MIS-C cases. NT-proBNP and troponin were consistently elevated (pooled means: 9697 pg/mL and 0.384 ng/mL, respectively), with a low risk of publication bias. Emerging biomarkers such as CXCL9, angiopoietin-2, and vitamin D revealed high inter-study variability but potential prognostic value. Subgroup analyses for selected studies (n = 5) suggested higher biomarker levels in severe MIS-C.

CONCLUSIONS

NT-proBNP and troponin are robust indicators of cardiac injury in MIS-C. Emerging biomarkers show promise but require validation. Future studies should include copeptin and adopt standardized reporting to refine biomarker-guided management.