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Multisystem Inflammatory Syndrome in U.S. Children and Adolescents

Our take —

This study was the largest to date to characterize multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection, which still appears to be relatively uncommon. The authors report on severe clinical illness affecting multiple organ systems. Most children were previously healthy, and most had laboratory evidence of current or prior SARS-CoV-2 infection. There was a broad spectrum of clinical outcomes, often including cardiovascular involvement, and a small number of deaths. It appears likely that MIS-C is an immune-mediated response to SARS-CoV-2 infection, but its timing and risk factors for its occurrence remain subjects of urgent inquiry.

Study design

Case Series

Study population and setting

The authors conducted nationwide surveillance in US pediatric health centers for cases of multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection from March 15 to May 20, 2020. The resulting case series comprised 186 patients (62% male, median age 8.3 years, 31% Hispanic/Latino, 25% Black non-Hispanic, 19% white non-Hispanic, 26% other/unknown) in 26 states, excluding 27 patients from a separate report from New York State. Criteria for the case definition were the following: hospitalization for serious illness; age < 21 years; fever ≥ 24 hours; laboratory evidence of inflammation; multisystem organ involvement; and evidence of SARS-CoV-2 infection from either PCR, antibody testing, or contact with known COVID-19 cases within the past month. Medical records were abstracted by clinicians at participating health centers via a standardized form.

Summary of Main Findings

The majority (n=131, 70%) of cases had laboratory evidence of SARS-CoV-2 infection on RT-PCR (n=73) or antibody test (n=58) , and the remainder had prior contact with a known COVID-19 case. Only 14 patients had a recorded date of COVID-19 symptom onset; among these, the median length of time before MIS-C symptom onset was 25 days (range 6-51). 73% of patients previously had been healthy. Four patients (2%) died, all of whom were 10-16 years old, and two of whom had underlying comorbidities. By the end of follow-up, 28% were still hospitalized, and 70% had been discharged alive. 90% of patients had fever for at least 4 days. At least four organ systems were involved in 71% of patients, with the most common being the gastrointestinal (90%), cardiovascular (80%), hematologic (76%), mucocutaneous (76%), and respiratory (74%) systems. Most (80%) patients were admitted to intensive care, 20% required invasive mechanical ventilation, and 4% required ECMO support. The median length of hospital stay was 7 days for those discharged alive. 48% of patients received vasoactive support, 73% had elevated BNP, and 50% had elevated troponin. 9% of patients with echocardiograms (n=171) had a coronary artery aneurysm. The vast majority (92%) of patients had elevated concentrations of at least 4 inflammatory biomarkers. Treatments varied according to presence of Kawasaki-disease-like symptoms, with intravenous immune globulin given to nearly all patients who exhibited 2 or more Kawasaki-like features. Other treatments included glucocorticoids (49%), anticoagulants (47%), IL-1Ra inhibitors (13%), and IL-6 inhibitors (8%).

Study Strengths

This study drew on a nationwide surveillance program for MIS-C, and records were extracted with a standardized form. Criteria for MIS-C were designed to be sensitive, but requiring laboratory-confirmed or epidemiologically suspected SARS-CoV-2 infection made this linkage highly plausible. The number of MIS-C patients included in this study is the largest to date.

Limitations

The interval between onset of COVID-19 symptoms and MIS-C symptoms was only available for a small subset of patients. Echocardiogram results were not available for all patients and varied in level of detail; this may have resulted in underreporting of coronary artery aneurysm and myocardial dysfunction. The lack of a comparison group precludes inference about risk factors. Since this was a retrospective review of records, SARS-CoV-2 testing was limited to respiratory samples and did not include systematic repeated testing of negative results. Determinants of selection for participating hospitals was not clear; results are not necessarily representative of the national population. This study excluded 27 cases from New York State which were included in a separate publication from the same journal, though a supplementary table includes the full population. Follow-up was incomplete for the 28% of cases still hospitalized.

Value added

This is the largest study to date of multisystem inflammatory syndrome in children related to SARS-CoV-2 infection, drawing on participating health care centers from across the United States.

This review was posted on: 10 July 2020