Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19
Journal
Nature medicine
Journal Volume
28
Journal Issue
5
Pages
1050
Date Issued
2022
Author(s)
Sacco, Keith
Castagnoli, Riccardo
Vakkilainen, Svetlana
Liu, Can
Delmonte, Ottavia M
Oguz, Cihan
Kaplan, Ian M
Alehashemi, Sara
Burbelo, Peter D
Bhuyan, Farzana
de Jesus, Adriana A
Dobbs, Kerry
Rosen, Lindsey B
Shaw, Elana
Vakkilainen, Mikko S
Pala, Francesca
Lack, Justin
Zhang, Yu
Fink, Danielle L
Oikonomou, Vasileios
Snow, Andrew L
Dalgard, Clifton L
Chen, Jinguo
Sellers, Brian A
Montealegre Sanchez, Gina A
Barron, Karyl
Rey-Jurado, Emma
Vial, Cecilia
Poli, Maria Cecilia
Licari, Amelia
Montagna, Daniela
Marseglia, Gian Luigi
Licciardi, Francesco
Ramenghi, Ugo
Discepolo, Valentina
Lo Vecchio, Andrea
Guarino, Alfredo
Eisenstein, Eli M
Imberti, Luisa
Sottini, Alessandra
Biondi, Andrea
Mató, Sayonara
Gerstbacher, Dana
Truong, Meng
Stack, Michael A
Magliocco, Mary
Bosticardo, Marita
Kawai, Tomoki
Danielson, Jeffrey J
Hulett, Tyler
Askenazi, Manor
Hu, Shaohui
Cohen, Jeffrey I
Su, Helen C
Kuhns, Douglas B
Lionakis, Michail S
Snyder, Thomas M
Holland, Steven M
Goldbach-Mansky, Raphaela
Tsang, John S
Notarangelo, Luigi D
Abstract
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.
Subjects
APOPTOSIS; DISEASE; IL-33; REPERTOIRE; REVEALS; VACCINE
SDGs
Publisher
NATURE PORTFOLIO
Type
journal article