biostudies-literatureSacco KIntramural NIH HHSNCI NIH HHS1050-1062https://www.ebi.ac.uk/biostudies/studies/S-EPMC9119950biostudies-literatureUnknown28(5)Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis of soluble biomarkers, proteomics, single-cell gene expression and immune repertoire analysis) to profile children with COVID-19 (n = 110) and MIS-C (n = 76), along with pediatric healthy controls (pHCs; n = 76). pCOVID-19 was characterized by robust type I interferon (IFN) responses, whereas prominent type II IFN-dependent and NF-κB-dependent signatures, matrisome activation and increased levels of circulating spike protein were detected in MIS-Nature medicineImmunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19.PMC9119950ZIA AI001265ZIA AI00127075N91019D00024Vakkilainen SMackey JSacco KTruong MAstudillo CHu SHulett TKuram VOler AJde Jesus AARastegar AGerstbacher DBosticardo MGuarino ARey-Jurado EGonzalez RBhuyan FLicari ALicciardi FLack JBurbelo PDSottini AMartins AJSu HCNIAID Immune Response to COVID GroupShyu CRosen LBPoli MCDalgard CLChen JCastagnoli RKaplan IMFink DLKawai TXirasagar SMatthews HDe Filippo MNotarangelo LDRamenghi UChile MIS-C GroupLo Vecchio AOikonomou VOguz CStack MAKuhns DBDiscepolo VTsang JSNambiar MMagliocco MCohen JICheng XEspinosa YBiondi APavia Pediatric COVID-19 GroupMato SVial CPalterer BMarseglia GLShaw EBansal NMMontealegre Sanchez GAHolland SMDelmonte OMKaladi KAskenazi MPala FBarnett JBarron KSnow ALCheng AWaingankar VPinera CGoldbach-Mansky RMudunuri USnyder TMSamuel SSellers BAEisenstein EMImberti LMontagna LVakkilainen MSZhang YDanielson JJDobbs KLionakis MSWeber SMontagna DVotto MAlehashemi SLiu CfalseImmunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19.Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis of soluble biomarkers, proteomics, single-cell gene expression and immune repertoire analysis) to profile children with COVID-19 (n = 110) and MIS-C (n = 76), along with pediatric healthy controls (pHCs; n = 76). pCOVID-19 was characterized by robust type I interferon (IFN) responses, whereas prominent type II IFN-dependent and NF-κB-dependent signatures, matrisome activation and increased levels of circulating spike protein were detected in MIS-2022-01-01T00:00:00Z2022 May2026-05-31T16:01:20.2Z2025-02-19T01:27:55.207ZS-EPMC91199503517786210.1038/s41591-022-01724-3