The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19

Rosat Consiglio, C.; Cotugno, N.; Sardh, F.; Pou, C.; Amodio, D.; Zicari, S.; Ruggiero, A.; Rubens Pascucci, G.; Rodriguez, L.; Santilli, V.; Tan, Z.; Eriksson, D.; Wang, J.; Lakshmikanth, T.; Marchesi, A.; Campana, A.; Villani, A.; Rossi, P.; the CACTUS study team,; Landegren, N.; Palma, P.; Brodin, P.

SARS-CoV2 infection is typically very mild and often asymptomatic in children. A complication is the rare Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever and organ dysfunction and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV2 and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, is more similar to Kawasaki disease, but also differ from this with respect to T-cell subsets, IL-17A and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests endoglin, an endothelial glycoprotein as one of several candidate targets of autoantibodies in MIS-C.