TY - JOUR
T1 - Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19
AU - NIAID Immune Response to COVID Group
AU - Chile MIS-C Group
AU - Pavia Pediatric COVID-19 Group
AU - Sacco, Keith
AU - Castagnoli, Riccardo
AU - Vakkilainen, Svetlana
AU - Liu, Can
AU - Delmonte, Ottavia M.
AU - Oguz, Cihan
AU - Kaplan, Ian M.
AU - Alehashemi, Sara
AU - Burbelo, Peter D.
AU - Bhuyan, Farzana
AU - de Jesus, Adriana A.
AU - Dobbs, Kerry
AU - Rosen, Lindsey B.
AU - Cheng, Aristine
AU - Shaw, Elana
AU - Vakkilainen, Mikko S.
AU - Pala, Francesca
AU - Lack, Justin
AU - Zhang, Yu
AU - Fink, Danielle L.
AU - Oikonomou, Vasileios
AU - Snow, Andrew L.
AU - Dalgard, Clifton L.
AU - Chen, Jinguo
AU - Sellers, Brian A.
AU - Montealegre Sanchez, Gina A.
AU - Barron, Karyl
AU - Rey-Jurado, Emma
AU - Vial, Cecilia
AU - Poli, Maria Cecilia
AU - Licari, Amelia
AU - Montagna, Daniela
AU - Marseglia, Gian Luigi
AU - Licciardi, Francesco
AU - Ramenghi, Ugo
AU - Discepolo, Valentina
AU - Lo Vecchio, Andrea
AU - Guarino, Alfredo
AU - Eisenstein, Eli M.
AU - Imberti, Luisa
AU - Sottini, Alessandra
AU - Biondi, Andrea
AU - Mató, Sayonara
AU - Gerstbacher, Dana
AU - Truong, Meng
AU - Stack, Michael A.
AU - Magliocco, Mary
AU - Bosticardo, Marita
AU - Kawai, Tomoki
AU - Danielson, Jeffrey J.
N1 - Publisher Copyright:
© 2022, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
PY - 2022/5
Y1 - 2022/5
N2 - 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-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.
AB - 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-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.
UR - http://www.scopus.com/inward/record.url?scp=85126232677&partnerID=8YFLogxK
U2 - 10.1038/s41591-022-01724-3
DO - 10.1038/s41591-022-01724-3
M3 - Article
C2 - 35177862
AN - SCOPUS:85126232677
SN - 1078-8956
VL - 28
SP - 1050
EP - 1062
JO - Nature Medicine
JF - Nature Medicine
IS - 5
ER -