tetano
Editor, Senior Moderator
Nat Med
. 2022 Feb 17.
doi: 10.1038/s41591-022-01724-3. Online ahead of print.
Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19
Keith Sacco[SUP] #[/SUP][SUP] 1 [/SUP], Riccardo Castagnoli[SUP] #[/SUP][SUP] 1 2 [/SUP], Svetlana Vakkilainen[SUP] #[/SUP][SUP] 1 [/SUP], Can Liu[SUP] #[/SUP][SUP] 3 4 [/SUP], Ottavia M Delmonte[SUP] 1 [/SUP], Cihan Oguz[SUP] 5 6 [/SUP], Ian M Kaplan[SUP] 7 [/SUP], Sara Alehashemi[SUP] 1 [/SUP], Peter D Burbelo[SUP] 8 [/SUP], Farzana Bhuyan[SUP] 1 [/SUP], Adriana A de Jesus[SUP] 1 [/SUP], Kerry Dobbs[SUP] 1 [/SUP], Lindsey B Rosen[SUP] 1 [/SUP], Aristine Cheng[SUP] 1 [/SUP], Elana Shaw[SUP] 1 [/SUP], Mikko S Vakkilainen[SUP] 9 [/SUP], Francesca Pala[SUP] 1 [/SUP], Justin Lack[SUP] 3 5 [/SUP], Yu Zhang[SUP] 1 [/SUP], Danielle L Fink[SUP] 10 [/SUP], Vasileios Oikonomou[SUP] 1 [/SUP], Andrew L Snow[SUP] 11 [/SUP], Clifton L Dalgard[SUP] 12 13 [/SUP], Jinguo Chen[SUP] 14 [/SUP], Brian A Sellers[SUP] 14 [/SUP], Gina A Montealegre Sanchez[SUP] 15 [/SUP], Karyl Barron[SUP] 16 [/SUP], Emma Rey-Jurado[SUP] 17 [/SUP], Cecilia Vial[SUP] 17 [/SUP], Maria Cecilia Poli[SUP] 17 18 [/SUP], Amelia Licari[SUP] 2 [/SUP], Daniela Montagna[SUP] 2 19 [/SUP], Gian Luigi Marseglia[SUP] 2 [/SUP], Francesco Licciardi[SUP] 20 [/SUP], Ugo Ramenghi[SUP] 20 [/SUP], Valentina Discepolo[SUP] 21 [/SUP], Andrea Lo Vecchio[SUP] 21 [/SUP], Alfredo Guarino[SUP] 21 [/SUP], Eli M Eisenstein[SUP] 22 [/SUP], Luisa Imberti[SUP] 23 [/SUP], Alessandra Sottini[SUP] 23 [/SUP], Andrea Biondi[SUP] 24 [/SUP], Sayonara Mató[SUP] 25 [/SUP], Dana Gerstbacher[SUP] 26 [/SUP], Meng Truong[SUP] 1 [/SUP], Michael A Stack[SUP] 1 [/SUP], Mary Magliocco[SUP] 27 [/SUP], Marita Bosticardo[SUP] 1 [/SUP], Tomoki Kawai[SUP] 1 [/SUP], Jeffrey J Danielson[SUP] 1 [/SUP], Tyler Hulett[SUP] 28 [/SUP], Manor Askenazi[SUP] 28 [/SUP], Shaohui Hu[SUP] 28 [/SUP], NIAID Immune Response to COVID Group; Chile MIS-C Group; Pavia Pediatric COVID-19 Group; Jeffrey I Cohen[SUP] 29 [/SUP], Helen C Su[SUP] 1 [/SUP], Douglas B Kuhns[SUP] 10 [/SUP], Michail S Lionakis[SUP] 1 [/SUP], Thomas M Snyder[SUP] 7 [/SUP], Steven M Holland[SUP] 1 [/SUP], Raphaela Goldbach-Mansky[SUP] 1 [/SUP], John S Tsang[SUP] 3 30 [/SUP], Luigi D Notarangelo[SUP] 31 [/SUP]
Collaborators, Affiliations
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.
. 2022 Feb 17.
doi: 10.1038/s41591-022-01724-3. Online ahead of print.
Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19
Keith Sacco[SUP] #[/SUP][SUP] 1 [/SUP], Riccardo Castagnoli[SUP] #[/SUP][SUP] 1 2 [/SUP], Svetlana Vakkilainen[SUP] #[/SUP][SUP] 1 [/SUP], Can Liu[SUP] #[/SUP][SUP] 3 4 [/SUP], Ottavia M Delmonte[SUP] 1 [/SUP], Cihan Oguz[SUP] 5 6 [/SUP], Ian M Kaplan[SUP] 7 [/SUP], Sara Alehashemi[SUP] 1 [/SUP], Peter D Burbelo[SUP] 8 [/SUP], Farzana Bhuyan[SUP] 1 [/SUP], Adriana A de Jesus[SUP] 1 [/SUP], Kerry Dobbs[SUP] 1 [/SUP], Lindsey B Rosen[SUP] 1 [/SUP], Aristine Cheng[SUP] 1 [/SUP], Elana Shaw[SUP] 1 [/SUP], Mikko S Vakkilainen[SUP] 9 [/SUP], Francesca Pala[SUP] 1 [/SUP], Justin Lack[SUP] 3 5 [/SUP], Yu Zhang[SUP] 1 [/SUP], Danielle L Fink[SUP] 10 [/SUP], Vasileios Oikonomou[SUP] 1 [/SUP], Andrew L Snow[SUP] 11 [/SUP], Clifton L Dalgard[SUP] 12 13 [/SUP], Jinguo Chen[SUP] 14 [/SUP], Brian A Sellers[SUP] 14 [/SUP], Gina A Montealegre Sanchez[SUP] 15 [/SUP], Karyl Barron[SUP] 16 [/SUP], Emma Rey-Jurado[SUP] 17 [/SUP], Cecilia Vial[SUP] 17 [/SUP], Maria Cecilia Poli[SUP] 17 18 [/SUP], Amelia Licari[SUP] 2 [/SUP], Daniela Montagna[SUP] 2 19 [/SUP], Gian Luigi Marseglia[SUP] 2 [/SUP], Francesco Licciardi[SUP] 20 [/SUP], Ugo Ramenghi[SUP] 20 [/SUP], Valentina Discepolo[SUP] 21 [/SUP], Andrea Lo Vecchio[SUP] 21 [/SUP], Alfredo Guarino[SUP] 21 [/SUP], Eli M Eisenstein[SUP] 22 [/SUP], Luisa Imberti[SUP] 23 [/SUP], Alessandra Sottini[SUP] 23 [/SUP], Andrea Biondi[SUP] 24 [/SUP], Sayonara Mató[SUP] 25 [/SUP], Dana Gerstbacher[SUP] 26 [/SUP], Meng Truong[SUP] 1 [/SUP], Michael A Stack[SUP] 1 [/SUP], Mary Magliocco[SUP] 27 [/SUP], Marita Bosticardo[SUP] 1 [/SUP], Tomoki Kawai[SUP] 1 [/SUP], Jeffrey J Danielson[SUP] 1 [/SUP], Tyler Hulett[SUP] 28 [/SUP], Manor Askenazi[SUP] 28 [/SUP], Shaohui Hu[SUP] 28 [/SUP], NIAID Immune Response to COVID Group; Chile MIS-C Group; Pavia Pediatric COVID-19 Group; Jeffrey I Cohen[SUP] 29 [/SUP], Helen C Su[SUP] 1 [/SUP], Douglas B Kuhns[SUP] 10 [/SUP], Michail S Lionakis[SUP] 1 [/SUP], Thomas M Snyder[SUP] 7 [/SUP], Steven M Holland[SUP] 1 [/SUP], Raphaela Goldbach-Mansky[SUP] 1 [/SUP], John S Tsang[SUP] 3 30 [/SUP], Luigi D Notarangelo[SUP] 31 [/SUP]
Collaborators, Affiliations
- PMID: 35177862
- DOI: 10.1038/s41591-022-01724-3
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.