Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory syndrome caused by the 2019 novel coronavirus (COVID-19). MIS-C can potentially damage multiple organ systems in previously healthy children and adolescents and may cause serious, life-threatening conditions, according to a study published in the New England Journal of Medicine.

The research team conducted both prospective and retrospective surveillance of patients with MIS-C who were admitted to participating health centers from March 15 to May 20, 2020. Clinicians who had knowledge of patients with MIS-C uploaded electronic health records into a database for review.

Six criteria were needed to meet MIS-C diagnosis: serious illness leading to hospitalization; patient aged <21 years, fever lasting at least 24 hours; laboratory evidence of inflammation; multisystem organ involvement; and laboratory-confirmed SARS-CoV-2 infection or exposure to a person with confirmed COVID-19 within 4 weeks of the onset of MIS-C symptoms. Kawasaki disease and associated signs and symptoms were also assessed among the patients with MIS-C. Organ-system involvement, specifically cardiovascular involvement, was defined on the basis of symptoms, clinical findings, and laboratory measures.

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A total of 186 patients were included in the study; of these, 164 (88%) were hospitalized between April 16 and May 20. The majority of patients (70%) tested positive for SARS-CoV-2 infections by RT-PCR, antibody testing, or both, and the remainder had an epidemiologic link to a person with COVID-19. “Almost one third of the patients tested negative for SARS-CoV-2 by RT-PCR but had detectable antibodies,” the researchers said. Median age of patients was 8.3 years; 62% were male, and 73% had previously been healthy.

A total of 71% of patients had involvement of at least 4 organ systems, including gastrointestinal (92%), cardiovascular (80%), hematologic, (76%), mucocutaneous (74%), and respiratory (70%) systems. Most patients were cared for in an intensive care unit (80%) and 20% received invasive mechanical ventilation. As of May 20, 2020, a total of 130 patients (70%) had been discharged, 52 (28%) were still hospitalized, and 4 (2%) had died. The 4 patients who died were aged 10 to 16 years; 2 of the children had underlying conditions.

Among all patients with MIS-C, at least 90% had fever for ≥4 days. In a small subgroup of patients, a median interval of 25 days was reported between the onset of COVID-19 symptoms and hospitalization for MIS-C. “Although not sufficient to establish causality, these findings suggest that a substantial proportion of the patients in this series were infected with SARS-CoV-2 at least 1 to 2 weeks before the onset of MIS-C,” the researchers said.

Almost half the patients (49%) received glucocorticoids, 8% received interleukin-6 inhibitors, 13% received an interleukin-1Ra inhibitor, and 77% received intravenous immune globulin.

A majority of patients (80%) had cardiovascular involvement; 48% of these received vasoactive support. A total of 91% of patients had at least 1 echocardiogram, and coronary-artery aneurysms were documented in 8% of patients. A subset of 74 patients (40%) has fever ≥5 days and had documented Kawasaki disease–like features. Intravenous immune globulin was given to all patients with 4 or 5 Kawasaki disease-like features and 97% of those with 2 or 3 features.

Respiratory insufficiency or failure occurred in 59% of patients; 78% of these patients had no underlying respiratory conditions. Overall 20% of patients received invasive mechanical ventilation and 17% received noninvasive mechanical ventilation.

Most patients had ≥4 laboratory biomarkers that indicated inflammation including elevated erythrocyte sedimentation rate, C-reactive protein, lymphocytopenia, neutrophilia, elevated ferritin level, hypoalbuminemia, elevated alanine aminotransferase level, anemia, thrombocytopenia and an elevated d-dimer level, prolonged international normalized ratio, and elevated fibrinogen level.

“Understanding the pathogenesis of MIS-C will be necessary to inform clinical management and prevention efforts,” concluded the study authors.


Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem inflammatory syndrome in US children and adolescents [published online June 29, 2020]. N Engl J Med. doi:10.1056/NEJMoa2021680.