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.
Reference
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.
