ABSTRACT
Background: The COVID-19-associated multisystem infammatory syndrome in children (MIS-C) is characterized by Kawasaki disease (KD)-like features and circulatory shock [1]. The genesis of SARS-CoV-2 variants triggered successive waves of mass infections followed by MIS-C outbreaks. Objectives: To compare MIS-C phenotypes across the waves of the COVID-19 pandemic. To identify predictors of pediatric intensive care unit (PICU) admission and treatment with biologic agents. Methods: Youth aged 0-18 years, fulflling the WHO case defnition of MIS-C, and admitted to the Alberta Children's Hospital during the COVID-19 pandemic (May 2020-December 2021) were included. Clinical, laboratory, imaging, and treatment data were captured (KD-like manifestations, signs of shock and/or hypotension, peak C-reactive protein (CRP) and ferritin, platelet count nadir, peak NT-proBNP and troponin, liver enzyme abnormalities, sodium and albumin nadir, echocardiogram fndings, biologic agents). Results: 57 consecutive MIS-C patients (median age 6 years, IQR 4-6;72% males) were included. 31 patients (54%) required PICU admission. All received immunoglobulins, 44 (77%) received corticosteroids, 8 patients (14%) were treated with biologic agents. Patients presenting during the third (mainly driven by Alpha variant) or fourth wave (mainly driven by Delta variant) presented with higher ferritin and NT-proBNP levels, and more liver enzyme abnormalities, hypoalbuminemia and thrombocytopenia compared to those presenting during the frst or second wave (Table 1, Figure 1). PICU admission was associated with the presence of shock/hypotension, higher CRP, ferritin, and NT-proBNP levels, lower albumin levels, and the presence of ventricular dysfunction on echocar-diogram (Table 1). A logistic regression model combining peak NT-proBNP, tro-ponin and ferritin levels explained 70% (Nagelkerke R2) of the variance in PICU admission and correctly classifed 91% of the cases. NT-proBNP was the sole signifcant contributor (p=0.017). Treatment with biologic agents was associated with higher CRP (mean 148.8 mg/l versus 251.7 mg/l;p=0.024) and ferritin (797 μg/l versus 1280 μg/l;p=0.049) levels. Conclusion: A shift in MIS-C phenotype was identifed across the successive COVID-19 waves, including the predominance of features associated with macrophage activation syndrome in later stages. These fndings may refect the impact of distinct SARS-CoV-2 variants. NT-proBNP emerged as the most important MIS-C feature predicting PICU admission, underscoring the importance of monitoring.