Management of COVID-19-associated multisystem inflammatory syndrome in children: A comprehensive literature review

Kiss, Andreea; Ryan, Paul MacDaragh; Mondal, Tapas

INTRODUCTION: The prevalence and severity of COVID-19 is greatly reduced in children, yet some pediatric patients develop a syndrome resembling Kawasaki Disease (KD), termed Multisystem Inflammatory Syndrome in Children (MIS-C). With an estimated incidence of 2/100,000 children, MIS-C is relatively rare, but can be fatal. Clinical features can include fever, hyperinflammatory state, gastrointestinal symptoms, myocardial dysfunction, and shock. The pathogenesis of MIS-C, although yet to be completely elucidated, appears to be distinct from KD in terms of epidemiology, severity, and biochemical signature. METHODS: This comprehensive review searched AMED, EBM Reviews, Embase, Healthstar, MEDLINE, ERIC, and Cochrane for studies that reported treatments and outcomes of MIS-C. RESULTS: The search strategy yielded 42 papers, from which 15 underwent full-text review (n = 386). A majority of children received intravenous immunoglobulin (77%) and some form of anticoagulation (63%). Steroid use was also common (44%), with immunotherapy used only in severe cases (n = 72). Outcomes reported included PICU admission (77%), need for extracorporeal membrane oxygenation (5%), and mortality (1.3%). Although efficacy of treatments for MIS-C have largely not yet been investigated, we propose close monitoring by a multidisciplinary team, symptomatic treatment (e.g., intravenous immunoglobulin for KD-like symptoms, steroids/immunotherapy for multisystem inflammation), and long-term follow-up. CONCLUSION: Although outcomes are largely favorable, management is based on a different disease entity (KD), which may not be appropriate given the likely pathophysiologic divergences. Further research is required to evaluate the effectiveness of current MIS-C treatments and to determine more refined therapies.