Unique cellular immune signatures of multisystem inflammatory syndrome in children

The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as acute COVID-19, Kawasaki disease, acute dengue, enteric fever, and systemic lupus erythematosus. We examined the ex-vivo cellular parameters with the aim of distinguishing MIS-C from other syndromes with overlapping clinical presentations. MIS-C children differed from children with non-MIS-C conditions by having increased numbers of naïve CD8+ T cells, naïve, immature and atypical memory B cells and diminished numbers of transitional memory, stem cell memory, central and effector memory CD4+ and CD8+ T cells, classical, activated memory B and plasma cells and monocyte (intermediate and non-classical) and dendritic cell (plasmacytoid and myeloid) subsets. All of the above alterations were significantly reversed at 6–9 months post-recovery in MIS-C. Thus, MIS-C is characterized by a distinct cellular signature that distinguishes it from other syndromes with overlapping clinical presentations. Trial Registration: ClinicalTrials.gov clinicaltrial.gov. No: NCT04844242. Author summary Multisystem inflammatory syndrome in children (MIS-C) is a severe disease that happens several weeks after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We performed an in-depth analysis of immune cell subsets and demonstrated that children with MIS-C had a distinctive cellular signature that differentiates it from other overlapping clinical presentations. T, B and myeloid cellular compartments were altered in MIS-C children. Post-recovery (6–9 months post-treatment), most of these alterations were significantly reversed and returned to normal levels. Thus, MIS-C varies from acute COVID-19, other infectious, non-infectious diseases and healthy pediatric controls by exhibiting a unique cellular signature.