Multisystem Inflammatory Syndrome in Children Associated with Severe Acute Respiratory Syndrome Coronavirus 2: A Systematic Review

Objective To develop a more comprehensive description of multisystem inflammatory syndrome in children (MIS-C), a novel syndrome linked to severe acute respiratory syndrome coronavirus 2, by conducting a systematic analysis of studies from different settings that used various inclusion criteria. Study design MIS-C studies were identified by searching PubMed and Embase as well as preprint repositories and article references to identify studies of MIS-C cases published from April 25, 2020, through June 29, 2020. MIS-C study metadata were assessed and information on case demographics, clinical symptoms, laboratory measurements, treatments, and outcomes were summarized and contrasted between studies. Results Eight studies were identified representing a total of 440 MIS-C cases. Inclusion criteria varied by study: 3 studies selected patients diagnosed with Kawasaki disease, 2 required cardiovascular involvement, and 3 had broader multisystem inclusion criteria. Median age of patients by study ranged from 7.3 to 10 years, and 59% of patients were male. Across all studies, the proportion of patients with positive results for severe acute respiratory syndrome coronavirus 2 reverse transcriptase-polymerase chain reaction tests ranged from 13% to 69% and for serology, from 75% to 100%. Patients with MIS-C had high prevalence of gastrointestinal (87%), dermatologic/ mucocutaneous (73%), and cardiovascular (71 %) symptoms. Prevalence of cardiovascular, neurologic, and respiratory system involvement significantly differed by study inclusion criteria. All studies reported elevated C-reactive protein, interleukin-6, and fibrinogen levels for at least 75% of patients in each study. Conclusions This systematic review of MIS-C studies assists with understanding this newly identified syndrome and may be useful in developing a refined, universal case definition of MIS-C.