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

Abstract

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.

Figure 2

Proportion of patients with clinical symptoms in different organ systems by study. Size of circles is relative to study sample size, and shapes represent categories of inclusion criteria. Gray bars represent the prevalence of organ system involvement in patients in all studies. Not all studies reported involvement for each organ system. Point labels denote studies: W = Whittaker, V = Verdoni, B = Belhadjer, T = Toubiana, D = Dufort, F = Feldstein, R = Ramcharan, and P = Pouletty. Studies with inclusion criteria of CVD and KD were assessed for differences in proportions compared with studies with broader inclusion criteria:, ∗P < .05, ∗∗P < .01, ∗∗∗P < .001. CVD, cardiovascular disorder; KD, Kawasaki disease; ns, not significant.

Figure 3

Proportion of patients receiving different types of treatment by study. Size of circles is relative to study sample size, and shapes represent categories of inclusion criteria. Gray bars represent the proportion of patients receiving treatments in all studies. Not all studies reported each type of treatment. Point labels denote studies: W = Whittaker, V = Verdoni, B = Belhadjer, T = Toubiana, D = Dufort, F = Feldstein, R = Ramcharan, and P = Pouletty. Studies with inclusion criteria of CVD and KD were assessed for differences in proportions compared with studies with broader inclusion criteria. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001.

Figure 1

Flowchart of literature search and study identification.