Background: Severe clinical manifestations of multisystem inflammatory syndrome in
children (MIS-C) are associated with the dysregulation of immune response following
SARS-CoV-2 infection. Therefore, we analyzed the levels of 10 selected cytokines at
admission to estimate disease severity and to predict the length of hospitalization.
In remission samples, these mediators were followed after intravenous immunoglobulin
(IVIG) treatment before discharge. Methods: Thirty-five MIS-C patients at the age
of 8.4 ± 4.1 years and 11 clinical controls were included. Acute MIS-C patients were
divided into two severity subgroups based on their clinical score determined by the
WHO criteria. Serum concentrations of IFN-γ, IL-1α, IL-1RA, IL-8, IL-10, IL-17A, IL-18,
IP-10, MCP-1, and TNF-α were measured by MILLIPLEX® Human Cytokine/Chemokine panel,
while ACE2 activity was determined by a fluorescent kinetic assay. These results were
correlated with routinely determined laboratory parameters and clinical characteristics.
Results: MIS-C patients demonstrated significantly elevated baseline levels of most
of these cytokines compared to controls. Even higher concentrations of IL-18, TNF-α
and ferritin with reduced lymphocyte count were found in severe subjects with elevated
clinical scores of 4–5 compared to moderate cases with a clinical score of 1–3. Furthermore,
the development of cardiovascular dysfunction and prolonged hospitalization (≥8 days)
were related to augmented ACE2 and IL-6 levels. IL-18, IL-1RA, IL-10 and TNF-α were
diminished in response to IVIG treatment in remission samples. Finally, pre-treatment
IL-18 (≥516.8 pg/mL) and TNF-α (≥74.2 pg/mL) effectively differentiated disease severity
in MIS-C with AUC values of 0.770 and 0.750, respectively. Conclusions: IL-18 and
TNF-α have a prognostic value in disease severity at admission and are capable of
monitoring the efficacy of IVIG treatment in MIS-C.
