Sacco, KeithKeithSaccoCastagnoli, RiccardoRiccardoCastagnoliVakkilainen, SvetlanaSvetlanaVakkilainenLiu, CanCanLiuDelmonte, Ottavia MOttavia MDelmonteOguz, CihanCihanOguzKaplan, Ian MIan MKaplanAlehashemi, SaraSaraAlehashemiBurbelo, Peter DPeter DBurbeloBhuyan, FarzanaFarzanaBhuyande Jesus, Adriana AAdriana Ade JesusDobbs, KerryKerryDobbsRosen, Lindsey BLindsey BRosenARISTINE CHENGShaw, ElanaElanaShawVakkilainen, Mikko SMikko SVakkilainenPala, FrancescaFrancescaPalaLack, JustinJustinLackZhang, YuYuZhangFink, Danielle LDanielle LFinkOikonomou, VasileiosVasileiosOikonomouSnow, Andrew LAndrew LSnowDalgard, Clifton LClifton LDalgardChen, JinguoJinguoChenSellers, Brian ABrian ASellersMontealegre Sanchez, Gina AGina AMontealegre SanchezBarron, KarylKarylBarronRey-Jurado, EmmaEmmaRey-JuradoVial, CeciliaCeciliaVialPoli, Maria CeciliaMaria CeciliaPoliLicari, AmeliaAmeliaLicariMontagna, DanielaDanielaMontagnaMarseglia, Gian LuigiGian LuigiMarsegliaLicciardi, FrancescoFrancescoLicciardiRamenghi, UgoUgoRamenghiDiscepolo, ValentinaValentinaDiscepoloLo Vecchio, AndreaAndreaLo VecchioGuarino, AlfredoAlfredoGuarinoEisenstein, Eli MEli MEisensteinImberti, LuisaLuisaImbertiSottini, AlessandraAlessandraSottiniBiondi, AndreaAndreaBiondiMató, SayonaraSayonaraMatóGerstbacher, DanaDanaGerstbacherTruong, MengMengTruongStack, Michael AMichael AStackMagliocco, MaryMaryMaglioccoBosticardo, MaritaMaritaBosticardoKawai, TomokiTomokiKawaiDanielson, Jeffrey JJeffrey JDanielsonHulett, TylerTylerHulettAskenazi, ManorManorAskenaziHu, ShaohuiShaohuiHuCohen, Jeffrey IJeffrey ICohenSu, Helen CHelen CSuKuhns, Douglas BDouglas BKuhnsLionakis, Michail SMichail SLionakisSnyder, Thomas MThomas MSnyderHolland, Steven MSteven MHollandGoldbach-Mansky, RaphaelaRaphaelaGoldbach-ManskyTsang, John SJohn STsangNotarangelo, Luigi DLuigi DNotarangelo2022-10-282022-10-2820221078-8956https://scholars.lib.ntu.edu.tw/handle/123456789/624134Pediatric 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-C, with no correlation with SARS-CoV-2 PCR status around the time of admission. Transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation. The association of MIS-C with the combination of HLA A*02, B*35 and C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load than pCOVID-19 and pHC. These results identify distinct immunopathological signatures in pCOVID-19 and MIS-C that might help better define the pathophysiology of these disorders and guide therapy.enAPOPTOSIS; DISEASE; IL-33; REPERTOIRE; REVEALS; VACCINE[SDGs]SDG3journal article10.1038/s41591-022-01724-3351778622-s2.0-85126232677WOS:000757243200002https://api.elsevier.com/content/abstract/scopus_id/85126232677