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Distinct phenotypes of multisystem inflammatory syndrome in children: a cohort study
Thomas Renson1,2, Nils D Forkert3, Kimberly Amador3
1Rheumatology, Department of Pediatrics, Alberta Children's Hospital, University of Calgary Cumming School of Medicine, 28 Oki Drive NW, Calgary, AB, T3B 6A8, Canada. thomas.renson@uzgent.be.
Insights
Later pandemic waves saw more severe multisystem inflammatory syndrome in children (MIS-C) cases, with higher NT-proBNP levels indicating intensive care needs. Monitoring NT-proBNP is crucial for managing MIS-C patients.
Area of Science:
- Pediatrics
- Infectious Diseases
- Cardiology
Background:
- Multisystem inflammatory syndrome in children (MIS-C) is a severe condition linked to COVID-19, posing a significant risk of cardiogenic shock.
- Understanding MIS-C's evolving presentation and risk factors is critical for timely intervention.
Purpose of the Study:
- To compare MIS-C phenotypes across different phases of the COVID-19 pandemic.
- To identify clinical and biochemical markers associated with intensive care unit (ICU) admission and the need for biologic therapies in MIS-C patients.
Main Methods:
- A cohort study included 57 pediatric patients (0-18 years) diagnosed with MIS-C between May 2020 and December 2021.
- Data on demographics, clinical presentation, laboratory values, imaging, and treatments were collected and analyzed.
- Unsupervised clustering was used to assess the classification of patients by pandemic wave and phase.
Main Results:
- Patients from later pandemic waves (phase 2) exhibited more severe phenotypes, with significantly higher levels of ferritin, NT-proBNP, and D-dimer.
- Later wave patients also showed increased prevalence of liver enzyme abnormalities, hypoalbuminemia, thrombocytopenia, and a higher need for respiratory support.
- NT-proBNP was identified as the sole significant predictor for intensive care needs across all regression models.
Conclusions:
- The evolving MIS-C phenotype during the pandemic suggests the influence of distinct SARS-CoV-2 variants.
- Elevated NT-proBNP levels are a key indicator for intensive care requirements in MIS-C.
- Close monitoring of NT-proBNP is essential for managing severe MIS-C cases.
Background:
Multisystem inflammatory syndrome in children (MIS-C) is a severe disease with an unpredictable course and a substantial risk of cardiogenic shock. Our objectives were to (a) compare MIS-C phenotypes across the COVID-19 pandemic, (b) identify features associated with intensive care need and treatment with biologic agents.
Methods:
Youth aged 0-18 years, fulfilling the World Health Organization case definition of MIS-C, and admitted to the Alberta Children's Hospital during the first four waves of the COVID-19 pandemic (May 2020-December 2021) were included in this cohort study. Demographic, clinical, biochemical, imaging, and treatment data were captured.
Results:
Fifty-seven MIS-C patients (median age 6 years, range 0-17) were included. Thirty patients (53%) required intensive care. Patients in the third or fourth wave (indicated as phase 2 of the pandemic) presented with higher peak ferritin (µg/l, median (IQR) = 1134 (409-1806) vs. 370 (249-629), P = 0.001), NT-proBNP (ng/l, median (IQR) = 12,217 (3013-27,161) vs. 3213 (1216-8483), P = 0.02) and D-dimer (mg/l, median (IQR) = 4.81 (2.24-5.37) vs. 2.01 (1.27-3.34), P = 0.004) levels, and higher prevalence of liver enzyme abnormalities (n(%) = 17 (68) vs. 11 (34), P = 0.02), hypoalbuminemia (n(%) = 24 (100) vs. 25 (81), P = 0.03) and thrombocytopenia (n(%) 18 (72) vs. 11 (34), P = 0.007) compared to patients in the first two waves (phase 1). These patients had a higher need of non-invasive/mechanical ventilation (n(%) 4 (16) vs. 0 (0), P = 0.03). Unsupervised clustering analyses classified 47% of the patients in the correct wave and 74% in the correct phase of the pandemic. NT-proBNP was the only significant contributor to the need for intensive care in all applied multivariate regression models. Treatment with biologic agents was significantly associated with peak CRP (mg/l (median, IQR = 240.9 (132.9-319.4) vs. 155.8 (101.0-200.7), P = 0.02) and ferritin levels (µg/l, median (IQR) = 1380 (509-1753) vs. 473 (280-296)).
Conclusions:
MIS-C patients in a later stage of the pandemic displayed a more severe phenotype, reflecting the impact of distinct SARS-CoV-2 variants. NT-proBNP emerged as the most crucial feature associated with intensive care need, underscoring the importance of monitoring.
