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%).
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.
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.
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