Cytokine Profiling among Children with Multisystem Inflammatory Syndrome versus Simple COVID-19 Infection: A Study from Northwest Saudi Arabia

SIMPLE SUMMARY: Multisystem Inflammatory Syndrome in Children (MIS-C) is a novel syndrome associated with COVID-19. Its manifestations vary from asymptomatic to life-threatening disease. Cytokines are essential mediators of the inflammatory response during MIS-C. In this study, we analyzed the expression of inflammatory markers and cytokines in blood, reported the important clinical characteristics, and correlated these results with short- and mid-term outcomes. Significantly elevated levels of cytokines (IL-1β, IL-6, and GM-CSF) confirmed their role in the severity of manifestations, disease progression, and outcome. Thus, this is one of the earliest studies in Saudi Arabia to evaluate the inflammatory response (cytokine profile) of MIS-C, correlating the clinical phenomena. ABSTRACT: Background: Multisystem Inflammatory Syndrome in Children (MIS-C) is a novel syndrome associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with varying clinical features. This study aimed to analyze the expression profiles of cytokines in blood, report the important clinical characteristics, and correlate these with the short- and mid-term outcomes. Methods: This cross-sectional study was conducted on hospitalized children with MIS-C from March 2021 to May 2022. Phenotypes were classified into two groups (A,B) according to the severity of the disease and the need for invasive respiratory support. Clinical features, laboratory parameters, and outcomes were reported. Results: We identified 60 children with MIS-C (mean age of 7.4 ± 3.8 years) compared to 30 age- and sex-matched controls with simple COVID-19. The clinical manifestations of MIS-C patients were fever (100%), respiratory (83.3%), GIT (80%), and conjunctivitis (80%). Twenty-seven MIS-C children (45%) required PICU admission due to shock and needed mechanical ventilation. Anemia, lymphopenia, and elevated levels of inflammatory and tissue injury markers were observed in the MIS-C groups (mainly B). High cytokine levels (IL-1β, IL-6, IFN-α, GM-CSF, and HMGB1) were observed acutely in the MIS-C children, and a persistent elevation of some cytokines were reported at midterm follow-up, especially in Group B. Conclusion: Robust inflammatory response to COVID-19 disease with elevated IL-1β, IL-6, and GM-CSF levels might explain the severity and outcome of the clinical syndrome.