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....

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Main Authors: Diana-Andreea Ciortea, Mădălina Nicoleta Matei, Mihaela Debita, Ancuța Lupu, Mirela Mătăsaru, Gabriela Isabela Verga (Răuță), Silvia Fotea
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Language:English
Published: MDPI AG 2025-05-01
Series:Life
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Online Access:https://www.mdpi.com/2075-1729/15/5/805
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author Diana-Andreea Ciortea
Mădălina Nicoleta Matei
Mihaela Debita
Ancuța Lupu
Mirela Mătăsaru
Gabriela Isabela Verga (Răuță)
Silvia Fotea
author_facet Diana-Andreea Ciortea
Mădălina Nicoleta Matei
Mihaela Debita
Ancuța Lupu
Mirela Mătăsaru
Gabriela Isabela Verga (Răuță)
Silvia Fotea
author_sort Diana-Andreea Ciortea
collection DOAJ
description 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.
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spelling doaj-art-e54e38bec3d0484bb8595c6c44e9e3cd2025-08-20T01:56:31ZengMDPI AGLife2075-17292025-05-0115580510.3390/life15050805Cardiac Manifestations and Emerging Biomarkers in Multisystem Inflammatory Syndrome in Children (MIS-C): A Systematic Review and Meta-AnalysisDiana-Andreea Ciortea0Mădălina Nicoleta Matei1Mihaela Debita2Ancuța Lupu3Mirela Mătăsaru4Gabriela Isabela Verga (Răuță)5Silvia Fotea6Faculty of Medicine and Pharmacy, “Dunarea de Jos” University of Galati, 800008 Galati, RomaniaFaculty of Medicine and Pharmacy, “Dunarea de Jos” University of Galati, 800008 Galati, RomaniaFaculty of Medicine and Pharmacy, “Dunarea de Jos” University of Galati, 800008 Galati, RomaniaDepartment of Mother and Child Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaFaculty of Medicine and Pharmacy, “Dunarea de Jos” University of Galati, 800008 Galati, RomaniaFaculty of Medicine and Pharmacy, “Dunarea de Jos” University of Galati, 800008 Galati, RomaniaFaculty of Medicine and Pharmacy, “Dunarea de Jos” University of Galati, 800008 Galati, RomaniaBackground: 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.https://www.mdpi.com/2075-1729/15/5/805multisystem inflammatory syndrome in children (MIS-C)biomarkersNT-proBNPtroponincopeptin
spellingShingle Diana-Andreea Ciortea
Mădălina Nicoleta Matei
Mihaela Debita
Ancuța Lupu
Mirela Mătăsaru
Gabriela Isabela Verga (Răuță)
Silvia Fotea
Cardiac Manifestations and Emerging Biomarkers in Multisystem Inflammatory Syndrome in Children (MIS-C): A Systematic Review and Meta-Analysis
Life
multisystem inflammatory syndrome in children (MIS-C)
biomarkers
NT-proBNP
troponin
copeptin
title Cardiac Manifestations and Emerging Biomarkers in Multisystem Inflammatory Syndrome in Children (MIS-C): A Systematic Review and Meta-Analysis
title_full Cardiac Manifestations and Emerging Biomarkers in Multisystem Inflammatory Syndrome in Children (MIS-C): A Systematic Review and Meta-Analysis
title_fullStr Cardiac Manifestations and Emerging Biomarkers in Multisystem Inflammatory Syndrome in Children (MIS-C): A Systematic Review and Meta-Analysis
title_full_unstemmed Cardiac Manifestations and Emerging Biomarkers in Multisystem Inflammatory Syndrome in Children (MIS-C): A Systematic Review and Meta-Analysis
title_short Cardiac Manifestations and Emerging Biomarkers in Multisystem Inflammatory Syndrome in Children (MIS-C): A Systematic Review and Meta-Analysis
title_sort cardiac manifestations and emerging biomarkers in multisystem inflammatory syndrome in children mis c a systematic review and meta analysis
topic multisystem inflammatory syndrome in children (MIS-C)
biomarkers
NT-proBNP
troponin
copeptin
url https://www.mdpi.com/2075-1729/15/5/805
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