Clinical presentation, diagnosis and management of multisystem inflammatory syndrome in children (MIS-C): a systematic review

Abstract

Background: Knowledge about multisystem inflammatory syndrome in children (MIS-C) is evolving, and evidence-based standardised diagnostic and management protocols are lacking. Our review aims to summarise the clinical and diagnostic features, management strategies and outcomes of MIS-C and evaluate the variances in disease parameters and outcomes between high-income countries (HIC) and middle-income countries (MIC).

Methods: We searched four databases from December 2019 to March 2023. Observational studies with a sample size of 10 or more patients were included. Mean and prevalence ratios for various variables were pooled by random effects model using R. A mixed generalised linear model was employed to account for the heterogeneity, and publication bias was assessed via funnel and Doi plots. The primary outcome was pooled mean mortality among patients with MIS-C. Subgroup analysis was conducted based on the income status of the country of study.

Results: A total of 120 studies (20 881 cases) were included in the review. The most common clinical presentations were fever (99%; 95% CI 99.6% to 100%), gastrointestinal symptoms (76.7%; 95% CI 73.1% to 79.9%) and dermatological symptoms (63.3%; 95% CI 58.7% to 67.7%). Laboratory investigations suggested raised inflammatory, coagulation and cardiac markers. The most common management strategies were intravenous immunoglobulins (87.5%; 95% CI 82.9% to 91%) and steroids (74.7%; 95% CI 68.7% to 79.9%). Around 53.1% (95% CI 47.3% to 58.9%) required paediatric intensive care unit admissions, and overall mortality was 3.9% (95% CI 2.7% to 5.6%). Patients in MIC were younger, had a higher frequency of respiratory distress and evidence of cardiac dysfunction, with a longer hospital and intensive care unit stay and had a higher mortality rate than patients in HIC.

Conclusion: MIS-C is a severe multisystem disease with better mortality outcomes in HIC as compared with MIC. The findings emphasise the need for standardised protocols and further research to optimise patient care and address disparities between HIC and MIC.

Prospero registration number: CRD42020195823.

Keywords: COVID-19; mortality.

Figure 1

Summary of key findings. This infographic provides a summary of all the key findings of our systematic review including the demographic, clinical and diagnostic features, management strategies and outcomes in multisystem inflammatory syndrome in children. It also displays the main differences in disease profile between high-income and middle-income countries. ECMO, extracorporeal membrane oxygenation; HIC, high-income countries; IL, interleukin; IVIG, intravenous immunoglobulins; LVEF, left ventricular ejection fraction; MIC, middle-income countries; PICU, paediatric intensive care unit.

Figure 2

Forest plot showing pooled estimates of mortality. The pooled estimates of the prevalence of mortality in multisystem inflammatory syndrome in children, with subgroup analysis between HIC and MIC using a generalised linear mixed model. Diamond indicates total estimates for each subgroup with 95% CI. GLMM, generalised linear mixed model; HIC, high-income countries; MIC, middle-income countries.