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Introduction: Multisystem inflammatory syndrome in children (MIS-C) is a new condition that first appeared in children and adolescents during the COVID-19 pandemic. We aimed to describe the diagnostic course, clinical and biological manifestations, and treatment of MIS-C during the first three COVID-19 waves. Methods: We extracted patient data from the Juvenile Inflammatory Rheumatism (JIR) cohort. We analyzed data for patients meeting the World Health Organization diagnostic criteria for MIS-C from the start of the COVID-19 pandemic from March 2020 to June 30, 2021. We then compared data for patients in wave one to those in waves two and three. Results: We identified 136 patients with MIS-C. The median age decreased but not significantly during the waves, from 9.9 years to 7.3 years (p = 0.105). Boys represented 52.2% (n = 71) of patients, and 46% (n = 41) of patients originated from sub-Saharan Africa (p < 0.001). Patients presented less diarrhea (p = 0.004), respiratory distress (p < 0.001), and myocarditis (p < 0.001) with progressive waves. Biological inflammation also decreased, namely, C-reactive protein level (p < 0.001), neutrophil count (p = 0.004), and albumin level (p < 0.001). Patients received more corticosteroids (p < 0.001) and required less ventilation support (p < 0.01) and less inotrope treatment (p < 0.001) in the later waves. The duration of hospitalization gradually decreased (p < 0.001), as did critical care unit admissions (p = 0.002). Conclusion: Over the three COVID-19 waves, with a change in the management of MIS-C, children in the JIR cohort in France showed a less severe disease course, in particular, a greater use of corticosteroids. This observation may reflect the impact of both improved management and different SARS-CoV-2 variant.
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Importance: Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown. Objective: To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. Design, Setting, and Participants: Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021. Exposures: IVIG and methylprednisolone vs IVIG alone. Main Outcomes and Measures: The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1. Results: Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P = .004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]). Conclusions and Relevance: Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.