Background: Multisystem inflammatory syndrome in children (MIS-C) is associated with SARS-CoV-۲. There are still controversial findings regarding the use of corticosteroids (CS) versus intravenous immunoglobulin (IVIG), and/or their combination in the management of MIS-C patients. This highlights the ongoing need for research to establish the most effective treatment approach.
Objectives: This systematic review and meta-analysis aimed to compare the outcomes of different immunomodulatory therapies (CS, IVIG, and IVIG + CS) in children with MIS-C.
Methods: This systematic review is reported based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The protocol was registered in PROSPERO (Code: CRD۴۲۰۲۳۳۸۹۹۶۴). A comprehensive literature search was conducted in May ۲۰۲۵ in PubMed, Web of Science, and Scopus for relevant articles published from January ۲۰۲۰ to December ۲۰۲۳. Studies including children and adolescents aged <۲۱ years with a confirmed MIS-C diagnosis, treated with CS and/or IVIG, were selected for the review. Outcomes were mortality, ICU admission, need for ventilation support, and length of hospital stay. The studies using propensity scores were included in the meta-analysis. Odds ratios (OR) and standardized mean differences (SMD) with ۹۵% confidence interval (CI) were estimated using a random-effects model to account for heterogeneity. Analyses were done in STATA software, version ۱۴.
Results: A total of ۱۲۳۲ records were identified through electronic database searches. Thirteen studies comprising ۴,۸۲۲ participants were included in the review. Ultimately, seven studies with propensity scores were included in the meta-analysis. Pooled analysis of seven studies indicated that the odds of requiring ventilator support (OR=۱.۶۷, ۹۵% CI, ۱.۲۷%, ۲.۲۱%, P<۰.۰۰۱) and mortality (OR=۲.۷۱, ۹۵% CI: ۱.۲۶%, ۵.۸۴%, P=۰.۰۱) were higher in the CS group compared to the IVIG group. The SMD for length of hospital stay among the three treatment groups was not statistically significant (P>۰.۰۵).
Conclusions: Current evidence suggests that IVIG may be effective as an initial treatment for patients with MIS-C. CS monotherapy is generally not recommended as the primary treatment for most patients. For critically ill children, the combination of IVIG with CS can potentially provide additional benefits. Further well-designed randomized controlled trials are necessary to more conclusively determine the optimal treatment strategy.