Long-term cytokine profile in multisystem inflammatory disease among children

Abstract

Background: Multisystem inflammatory disease in children (MIS-C) is a post-infectious condition following coronavirus disease-19 infection. Long-term follow-up data suggests that initial clinical severity does not necessarily correlate with long-term outcomes. The long-term immunological response in children with MIS-C remains poorly understood. We analyzed cytokine profiles at diagnosis and during follow-up, in pediatric patients with MIS-C, exploring correlations among cytokine expressions and standard biochemical and hormonal test results.

Methods: Twenty-five MIS-C patients (mean 9.4 ± 3.9) with complete test results at diagnosis and at 6- and 12-months follow-up were included in the study. Selected cytokines, such as IL-9, eotaxin, IP-10, MIP-1β, RANTES, MCP-1(MCAF), TNF-α, PDGF-B, IL-4, and MIP-1α, were included in the analysis.

Results: IP-10, MCP-1 (MCAF), and MIP-1α levels normalized or nearly normalized at 6-12 months, the remaining cytokines, including IL-9, eotaxin, MIP-1β, RANTES, TNF-α, PDGF-B, IL-4, remained higher in MIS-C than in controls at our last follow-up time. At 6 months post-diagnosis, a mild negative correlation between triglycerides and HOMA-IR with MCP-1 (MCAF), IL-4, and Eotaxin was noted. At the 12-month follow-up we found a mild positive correlation of cortisol and ACTH levels with PDGF-B, MIP-1α, and TNF-α. Conversely, a negative correlation between these cytokines with fasting glucose and HOMA-IR was observed.

Conclusions: Our study findings highlight a notable cytokine-mediated inflammatory response in pediatric patients with MIS-C, characterized by sustained elevated levels over a 12-month monitoring period compared to the control group. We have identified various interrelationships among different cytokines, as well as correlations between heightened cytokine levels and metabolic and hormonal patterns. The pronounced inflammatory response underscores its involvement in acute organ damage, while its persistence suggests potential implications for long-term metabolic disorders.

Keywords: COVID-19; Children; Complications; Cytokines; Long-term follow-up; Multisystem inflammatory disease.