Severity and Incidence of Multisystem Inflammatory Syndrome in Children During 3 SARS-CoV-2 Pandemic Waves in Israel

PURPOSE OF STUDY: Multisystem inflammatory syndrome in children (MIS-C) is a serious complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The authors describe outcomes of MIS-C in a multicenter cohort and assessed incidence nationally during the α, Δ, and ο variant waves. STUDY POPULATION: Israeli children admitted for treatment with MIS-C during the COVID-19 pandemic. METHODS: To assess cardiac involvement and admission to the ICU in patients with MIS-C, a prospective study was conducted in 12 Israeli hospitals over a 16-week period of each pandemic wave. These participating institutions account for approximately 70% of the admissions to PICUs in Israel. Data of all patients with MIS-C younger than 18 years from the α (December 20, 2020, to April 10, 2021), Δ (July 18, 2021, to November 13, 2021), and ο (November 21, 2021, to March 12, 2022) waves were prospectively collected. Vaccination status was determined by reviewing the SARS-CoV-2 digital vaccination record. The MIS-C definition was based on Centers for Disease Control and Prevention criteria. RESULTS: In the 12 participating hospitals, 171 patients with a median (interquartile range) age of 8 (5–12) years were diagnosed with MIS-C;59 during the α wave, 79 during the Δ wave, and 33 during the ο wave. Ninety-four patients (55%) were males. All patients were treated with intravenous immunoglobulins and steroids. In 5 of 79 patients (6.3%) during the Δ wave and 5 of 33 (15.1%) during the ο wave, a second SARS-CoV-2 vaccine dose had been administered at least 2 weeks before hospital admission. None of the vaccinated patients were admitted to the ICU or required treatment with vasopressors. Cardiac outcomes were more favorable during the ο wave. Admission to the ICU occurred in 34 participants (57.6%) during the α wave, 39 (49.4%) during Δ, and 7 (21.2%) during ο, and median hospital length of stay was 2 days shorter during ο than the α and Δ waves. Vasopressors were used in 22% of patients during α, 17.7% during Δ, and 6.0% during ο, and mechanical ventilation was used in 8.5% of patients during α, 8.9% during Δ, and in no patients during ο. One patient died during the Δ wave. Nationwide, in persons younger than 18 years, there were 188 800 SARS-CoV-2 infections and 103 patients with MIS-C during α, 233 585 SARS-CoV-2 infections and 115 patients with MIS-C during Δ, and 946 779 SARS-CoV-2 infections and 36 patients with MIS-C during ο. MIS-C incidences per 100 000 persons younger than 18 years were 54.5 during α, 49.2 during Δ, and 3.8 during ο. There was a higher incidence of MIS-C among patients during the α wave (incidence rate ratio, 14.34 [95% confidence interval, 9.81–20.96]) and Δ wave (incidence rate ratio, 12.94 [95% confidence interval, 8.90–18.81]) compared with the ο wave. CONCLUSIONS: This study suggests that MIS-C during the ο wave was less severe than during the α or Δ waves of the coronavirus disease 2019 pandemic. Possible explanations include the ο variant itself, previous infection with SARS-CoV-2, vaccination against SARS-CoV-2, and improvement in treatment over time. In addition, the incidence rate of MIS-C during the ο wave was lower than during the Δ and α waves. Limitations of the study include the small number of patients in the prospective cohort and the single-country data. Because MIS-C is a late-onset phenomenon of SARS-CoV-2 infection, cases that appeared after the 16-week period of each wave were not included.