What we now know about multisystem inflammatory syndrome in children

In May 2020, a previous AFP Community Blog post described an emerging COVID-19 associated, Kawasaki disease-like syndrome that became known as multisystem inflammatory syndrome in children (MIS-C). (The Centers for Disease Control and Prevention later identified a similar inflammatory syndrome in adults, MIS-A.) Over the past year, as family physicians, pediatricians, and children's hospitals have gained experience with treating patients with MIS-C, we now know more about differentiating it from Kawasaki disease and managing its major complications. A review article by Drs. John Darby and Jennifer Jackson in the September issue of AFP provided an overview and comparison of Kawasaki disease and MIS-C. Although Kawasaki disease primarily occurs in toddlers, MIS-C has been observed in patients from one week to 20 years of age, with a median age of 7 to 9 years. In the U.S., Hispanic and non-Hispanic Black children have been disproportionately affected by MIS-C, comprising 62% of all cases. Vomiting, diarrhea, and abdominal pain occur in 80% of patients, while neurocognitive symptoms affect about 20%. Additional symptoms of MIS-C can include hypotension secondary to cardiac dysfunction and systemic vasodilation.

Two observational studies of patients with MIS-C published in June 2021 added to the knowledge base but did not definitively identify the most appropriate treatment. A propensity-score matched analysis of 518 patients admitted to U.S. hospitals for MIS-C between March 15 and October 31, 2020 found that initial treatment with intravenous immune globulin (IVIG) plus glucocorticoids, compared to IVIG alone, was associated with a reduced risk of new or persistent cardiovascular dysfunction (a composite outcome of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2 of admission. In contrast, an international cohort study of 614 children with suspected MIS-C from 32 countries treated from June 2020 through February 2021 found no differences in a composite outcome of inotropic support or mechanical ventilation by day 2 or later between children who received IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone.

A longitudinal cohort study of 50 patients admitted to a single U.S. medical center between April and June 2020 reported outcomes of MIS-C at 6 months. 31 patients required intensive care, and 33 developed left ventricular dysfunction, coronary dilation, or aneurysms. The mean length of stay was 5 days. After two weeks, only 9 patients had persistent ventricular dysfunction or other coronary abnormalities, though nearly half reported fatigue with ordinary activities. All 25 patients who presented for a 6-month follow-up visit were asymptomatic, with a single patient having left ventricular diastolic dysfunction. Although the rapid resolution of symptoms and cardiac abnormalities seen in this study is good news, it is unclear if these outcomes will persist given the much greater number of children with COVID-19 infections who were hospitalized during the summer of 2021. The best approach to preventing MIS-C remains reducing the risk of SARS-CoV-2 infection through vaccinating adolescents and - pending regulatory approval in the next few weeks - younger children.