The difference of the inflammatory milieu in MIS-C and severe COVID-19

Abstract

Background Coronavirus disease 19 (COVID-19) may have a severe course in children. Multisystem inflammatory syndrome in children (MIS-C) is the post-COVID complication characterized by an exaggerated inflammation, observed in children. However, data on the underlying pathophysiology are sparse. We therefore aimed to assess the cytokine and chemokine profiles of children with MIS-C and compare these to life-threatening severe SARS-CoV-2 and healthy controls (HCs) to shed light on disease pathophysiology. Methods Samples of 31 children with MIS-C, 10 with severe/critical COVID-19 and 11 HCs were included. Cytokine and chemokine profiles were studied and compared in between groups. Results Most cytokines and chemokines related to IL-1 family and IFN-γ pathway (including IL-18 and MIG/CXCL9) and IL-17A were significantly higher in the MIS-C group when compared to the severe/critical COVID-19 group and HCs. IP-10/CXCL10 and IL-10 were higher in both MIS-C patients and severe/critical COVID-19 compared to HCs. Conclusion Our results suggest that IL-1 and IFN-γ pathways play an important role in the pathophysiology of MIS-C. Impact This study defines a pattern of distinctive immune responses in children with MIS-C and in patients with severe/critical COVID-19. As the COVID-19 pandemic continues, biomarkers to identify MIS-C risk are needed to guide our management that study results may shed light on it.

IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohort

“…The up-regulation of IL-1, IL-4 and IL-13 pathways in MIS-C is in accordance with previous reports in which these cytokines have been elevated in MIS-C serum (17,(30)(31)(32). IL-1 blockade has been used in the treatment of MIS-C and KD, and recently anti-IL-1Ra autoantibodies have been described in over 60% of MIS-C patients while absent in healthy controls and patients with COVID-19 (33).…”

Clinical characteristics of children with MIS-C fulfilling classification criteria for macrophage activation syndrome

“…They found that 13 (41.9%) of 31 MIS-C patients fulfilled 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis. Patients with MIS-C that met MAS criteria had higher levels of IL-17A and IFN-γ than those who did not fulfill the criteria; however, it was not statistically significant ( 40 ). Rodriguez-Smith et al reported that eight (42%) of 19 patients with MIS-C who met MAS criteria (also based on 2016 MAS classification) had significantly higher CXCL9 concentration than patients with MIS-C without MAS.…”

“…Because there are no specific criteria for diagnosis of MAS in MIS-C and given clinical and laboratory features of MIS-C that resemble MAS, 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis were previously applied to MIS-C ( 2 , 40 , 41 ).…”

IL-10 suppresses T cell expansion while promoting tissue-resident memory cell formation during SARS-CoV-2 infection in rhesus macaques

“…IFNg and molecules induced by IFNgR signaling (e.g., CXCL10) have been associated with severe COVID-19 and the development of acute respiratory distress syndrome (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Elevated levels of IFNg also strongly correlate with the development of multi-system inflammatory syndrome in children after SARS-CoV-2 infection (8,13,14).…”

“…IFNγ and molecules induced by IFNγR signaling (e.g., CXCL10) have been associated with severe COVID-19 and the development of acute respiratory distress syndrome ( 3–12 ). Elevated levels of IFNγ also strongly correlate with the development of multi-system inflammatory syndrome in children after SARS-CoV-2 infection ( 8, 13, 14 ). In ACE2 transgenic mice, neutralizing IFNγ along with TNF reduced mortality of severe SARS-CoV-2 infection ( 7, 15 ).…”