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  1. T. Renson1,
  2. P. Miettunen2,3,
  3. S. Parsons4,
  4. M. Dhalla3,
  5. N. Johnson2,3,
  6. N. Luca2,3,
  7. H. Schmeling2,3,
  8. R. Stevenson3,
  9. M. Twilt2,3,
  10. L. Hamiwka2,5,
  11. S. Benseler2,3
  1. 1Alberta Children’s Hospital, Rheumatology and Nephrology, Calgary, Canada
  2. 2Alberta Children’s Hospital Research Institute, Cumming School of Medicine, Calgary, Canada
  3. 3Alberta Children’s Hospital, Rheumatology, Calgary, Canada
  4. 4Alberta Children’s Hospital, Critical Care Medicine, Calgary, Canada
  5. 5Alberta Children’s Hospital, Nephrology, Calgary, Canada


Background The COVID-19-associated multisystem inflammatory 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, fulfilling the WHO case definition 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 findings, 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 first 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 echocardiogram (Table 1). A logistic regression model combining peak NT-proBNP, troponin and ferritin levels explained 70% (Nagelkerke R2) of the variance in PICU admission and correctly classified 91% of the cases. NT-proBNP was the sole significant 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.

Table 1.

Upper panel: Differences in MIS-C features of patients presenting during the first phase of the COVID-19 pandemic (first + second wave) compared to those presenting during the second phase (third + fourth wave) (*one missing value). Lower panel: Differences regarding MIS-C features between patients admitted to PICU compared to those managed on the general ward.

Figure 1.

Violin plots depicting differences in key laboratory MIS-C features between the waves (A) and both phases (phase 1 = wave 1 + 2, phase 2 = wave 3 + 4; B) of the COVID-19 pandemic.

Conclusion A shift in MIS-C phenotype was identified across the successive COVID-19 waves, including the predominance of features associated with macrophage activation syndrome in later stages. These findings may reflect 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.

References [1]Riphagen S, Gomez X, Gonzalez-Martinez C, et al. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 2020;395(10237):1607–8

Disclosure of Interests None declared

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