Multisystem inflammatory syndrome in children (MIS-C) is a rare, but severe complication of coronavirus disease 2019 (COVID-19). It develops approximately four weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and involves hyperinflammation with multisystem injury, commonly progressing to shock. The exact pathomechanism of MIS-C is not known, but immunological dysregulation leading to cytokine storm plays a central role. In response to the emergence of MIS-C, the European Academy of Allergy and Clinical Immunology (EAACI) established a task force (TF) within the Immunology Section in May 2021. With the use of an online Delphi process, TF formulated clinical statements regarding immunological background of MIS-C, diagnosis, treatment, follow-up, and the role of COVID-19 vaccinations. MIS-C case definition is broad, and diagnosis is made based on clinical presentation. The immunological mechanism leading to MIS-C is unclear and depends on activating multiple pathways leading to hyperinflammation. Current management of MIS-C relies on supportive care in combination with immunosuppressive and/or immunomodulatory agents. The most frequently used agents are systemic steroids and intravenous immunoglobulin. Despite good overall short-term outcome, MIS-C patients should be followed-up at regular intervals after discharge, focusing on cardiac disease, organ damage, and inflammatory activity. COVID-19 vaccination is a safe and effective measure to prevent MIS-C. In anticipation of further research, we propose a convenient and clinically practical algorithm for managing MIS-C developed by the Immunology Section of the EAACI.

BACKGROUND: Lymphopenia is a hallmark of multisystem inflammatory syndrome in children (MIS-C). We aimed to characterize lymphocyte subsets’ shifts and their correlations with other severity markers of MIS-C. METHODS: In this prospective cross-sectional study, we performed peripheral lymphocyte phenotyping in 32 patients with MIS-C. We analyzed lymphocyte subsets at three time-points of the disease: the acute (A), convalescent (B), and recovery (C) phases. Based on age-normalized lymphocyte counts, we distinguished two groups of patients: “the mild” and “the severe”. In addition, we examined differences between these groups regarding other severity markers. RESULTS: In phase A, 84% of children had lymphopenia. Decreased absolute counts of CD3, CD4, and CD8 cells were observed in, respectively, 88%, 72%, and 84% of patients. The natural killer cells were decreased in 63% and CD19 in 59% of children. “The severe” group had significantly higher procalcitonin and troponin I levels and lower platelets and albumin. Moreover, “the severe” group had hypotension more frequently (73% vs. 20%, p=0.008). In phase B, all lymphocyte counts increased, and 32% of children had lymphocytosis. The increase of CD3, CD4, and CD8 counts correlated with some laboratory severity markers (hemoglobin, procalcitonin, D-dimer, lactate dehydrogenase, N-terminal prohormone of brain natriuretic peptide, albumin), but not with steroid use. In phase C, most children had normal lymphocyte counts. CONCLUSIONS: Substantial shifts in lymphocyte counts during MIS-C apply most to T lymphocytes and correlate with the disease severity markers, particularly hypotension prevalence. A proportion of children with MIS-C develops transient lymphocytosis during convalescence.