Nevertheless, the temporal trajectory of inflammatory markers in response to treatment during the course of the disease has not been elucidated. The magnitude of the inflammatory response in MIS-C correlates with disease severity 13, 16, and use of glucocorticoids and intravenous immunoglobulins (IVIGs) improves clinical outcome 17, whereas limited data are available on the efficacy of biologics, such as IL-1 receptor (IL-1R) and tumor necrosis factor-α (TNF-α) antagonists and tocilizumab 18, 19. Elevated serum levels of several inflammatory biomarkers, an expansion of T cell clonotypes expressing the T cell receptor (TCR) TRBV11-2 gene (possibly in response to a SARS-CoV-2 superantigen) and presence of auto-antibodies directed against several self-antigens have been reported in MIS-C 11, 12, 13, 14, 15. More limited information is available on the immune response to acute SARS-CoV-2 infection in children 10. Older age, male sex, obesity, co-existing comorbidities, genetic defects of Toll-like receptor 3 (TLR3)-dependent and TLR7-dependent type I IFN pathways and neutralizing auto-antibodies against type I IFNs are associated with more severe clinical outcomes in adults with COVID-19 (aCOVID-19) 6, 7, 8, 9. The mechanisms underlying the different picture of pCOVID-19 and MIS-C remain ill-defined. However, approximately 3–4 weeks after exposure to SARS-CoV-2, some children develop a hyperinflammatory response resembling Kawasaki disease (KD) and toxic shock syndrome that has been termed MIS-C 3, 4, 5. 1), although severe cases and fatal outcomes have been also reported 2. 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.Īfter infection with SARS-CoV-2, most children develop mild and self-limiting symptoms of COVID-19 (ref. MIS-C B cells showed higher mutation load than pCOVID-19 and pHC. The association of MIS-C with the combination of HLA A*02, B*35 and C*04 alleles suggests genetic susceptibility. Transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation.

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.

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). 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.

Nature Medicine volume 28, pages 1050–1062 ( 2022) Cite this article Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19

Immune repertoire and disease