Markers for the Severity of Multisystem Inflammatory Syndrome in Children: A Multivariate Analysis
Open Access
- 1 January 2026
- journal article
- Published by Wiley in International Journal of Pediatrics
- Vol. 2026 (1)
Abstract
Background: Our goals were to find and grade children with multisystem inflammatory syndrome (MIS‐C) by clinical severity and the degree of different system involvement based on multivariate clinical laboratory data and identify the best predictors and scores for disease prognosis and risk stratification. Methods: We enrolled 51 patients with confirmed MIS‐C from a single center, and 34 general laboratory parameters and markers were included. Results: Using the K ‐means clustering method on kernel principal component analysis (K‐PCA) projections, we identified that our MIS‐C patients could be separated into three clusters. Children belonging to Cluster 3 have the highest levels of ferritin, LDH, ASAT, ALAT, GGT, total bilirubin, direct bilirubin, azotemia, urea, and creatinine, followed by Cluster 2. In contrast, Cluster 1 showed the lowest levels, p < 0.05. Children belonging to Clusters 3 and 2 also needed inotropic support significantly more frequently than Cluster 1 (30% and 10% vs 0%, Fisher exact test p = 0.04). Furthermore, respiratory distress was found only in patients of Clusters 2 and 3 ( p = 0.002). Regarding liver involvement, Clusters 2 and 3 more frequently had cholestasis (61% and 75% vs. 28%, p = 0.012), whereas Cluster 3 was more prominently characterized by an enlarged liver (44% vs. 0% and 5%, p = 0.004). Therefore, our clusters represent different grades, and liver and kidney involvement stages are graded by severity. From ROC curve analysis and several logistic regressions, we identified that age equal to or higher than 9 years old and ferritin levels higher than 470 ng/mL could help distinguish children with more severe kidney and liver involvement with a high probability (ROC AUC = 77 % , p = 0.03 and ROC AUC = 75 % , p = 0.04) approximately equal to the discriminatory potential of creatinine, urea, GGT and total bilirubin. Moreover, levels of LDH with a cutoff of 363 U/l could identify the children within Cluster 3 (ROC AUC = 80 % , p = 0.004). Conclusions: LDH and ferritin, as well as age into consideration, could help the clinical assessment of the underlying severity.Keywords
This publication has 13 references indexed in Scilit:
- Serum ferritin as a predictive biomarker in COVID-19. A systematic review, meta-analysis and meta-regression analysisJournal of Critical Care, 2021
- Liver Involvement in Children with COVID-19 and Multisystem Inflammatory Syndrome: A Single-Center Bulgarian Observational StudyMicroorganisms, 2021
- Acute kidney injury in pediatric patients hospitalized with acute COVID-19 and multisystem inflammatory syndrome in children associated with COVID-19Kidney International, 2021
- Multisystem inflammatory syndrome in children and adults (MIS-C/A): Case definition & guidelines for data collection, analysis, and presentation of immunization safety dataVaccine, 2021
- Systemic inflammation as fuel for acute liver injury in COVID-19Digestive and Liver Disease, 2021
- Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentationsBlood Advances, 2020
- Acute Kidney Injury in Pediatric Inflammatory Multisystem Syndrome Temporally Associated With Severe Acute Respiratory Syndrome Coronavirus-2 Pandemic: Experience From PICUs Across United Kingdom*Critical Care Medicine, 2020
- Multisystem inflammatory syndrome in children: A systematic revieweClinicalMedicine, 2020
- COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort studyThe Lancet Child & Adolescent Health, 2020
- Iron: Innocent bystander or vicious culprit in COVID-19 pathogenesis?International Journal of Infectious Diseases, 2020