Tracking the soluble biomarkers of MIS-C and their association with clinical parameters and severity.

Abstract

Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe post-COVID-19 complication characterized by hyperimmune activation and systemic inflammation. Identifying biomarkers for disease severity and predicting ICU admission is critical. This study analyzed 92 inflammatory biomarkers in serum samples from 22 pediatric MIS-C patients and 17 convalescent COVID-19 children using Olink proteomics. MIS-C samples were taken at diagnosis, before treatment, and at follow-up. Convalescent COVID-19 samples were taken 3 to 5 weeks after acute COVID-19 diagnosis, at a similar time to MIS-C theoretical occurrence. The study identified 29 significantly altered biomarkers in MIS-C, including elevated pro-inflammatory cytokines (IFN-γ, IL-6, TNF, IL-18), chemokines (CXCL9, CXCL10, CXCL11), and immune regulators (IL-10, PD-L1, CDCP1). Among these, random forest analysis highlighted 18 key markers distinguishing MIS-C from convalescent cases. ICU-admitted MIS-C patients displayed distinct biomarker signatures, and the differential regulation of IL-2, IL-33, CD244, SCF, TNFRSF9, and CD8α, was sufficient to predict almost all ICU admissions. Notably, lower levels of soluble CD244 and TNFRSF9 correlated with longer hospital stays. Finally, longitudinal analysis showed biomarker normalization within two months post-MIS-C. This study provides a detailed characterization of the MIS-C inflammatory response, identifying potential biomarkers for improved early diagnosis and clinical management. MIS-C incidence has substantially decreased since the beginning of the COVID-19 pandemic, but rare cases are still occurring with severe to critical presentation. We identified 6 biomarkers, IL-2, IL-33, CD244, SCF, TNFRSF9, and CD8α, predictors of ICU-admission in MIS-C. We showed the normalization of cytokine profiles by 2 months following treatment in MIS-C. This study Identified potential biomarkers for improved early diagnosis and clinical management of MIS-C.