Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19

Abstract

Importance: Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes.

Objective: To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19).

Setting, design, and participants: Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement.

Exposure: SARS-CoV-2.

Main outcomes and measures: Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19.

Results: Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P < .001), higher C-reactive protein level (median, 152 mg/L vs 33 mg/L; P < .001), and lower platelet count (<150 ×103 cells/μL [212/523 {41%} vs 84/486 {17%}, P < .001]). A total of 398 patients (73.8%) with MIS-C and 253 (43.8%) with COVID-19 were admitted to the intensive care unit, and 10 (1.9%) with MIS-C and 8 (1.4%) with COVID-19 died during hospitalization. Among patients with MIS-C with reduced left ventricular systolic function (172/503, 34.2%) and coronary artery aneurysm (57/424, 13.4%), an estimated 91.0% (95% CI, 86.0%-94.7%) and 79.1% (95% CI, 67.1%-89.1%), respectively, normalized within 30 days.

Conclusions and relevance: This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19.

Figure 1.. Eligibility Flowchart of Hospitalized Patients With COVID-19–Related Illness, March 15-October 31, 2020

COVID-19 indicates coronavirus disease 2019; RT-PCR, reverse transcriptase–polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; and MIS-C, multisystem inflammatory syndrome in children. ^aRegistry data was based on voluntary case reporting by participating sentinel surveillance sites. ^bCriteria for registry: meet case definition for MIS-C (Box 1) or evidence of infection with SARS-CoV-2 based on a positive RT-PCR test result during current illness with clinical suspicion for acute COVID-19.

Figure 2.. Multivariable Analyses of MIS-C vs COVID-19

COVID-19 indicates coronavirus disease 2019 and MIS-C, multisystem inflammatory syndrome in children. ^aIncluded children and adolescents younger than 21 years of age from 66 hospitals in 31 states from March 15 to October 31, 2020. ^bAbsolute row differences in characteristic between patients with MIS-C and COVID-19 with exact confidence intervals; a positive value indicates that the characteristic was more common in children and adolescents diagnosed with MIS-C. ^cThe primary outcome is diagnosis of MIS-C vs COVID-19. A risk ratio greater than 1 represents a higher relative risk of MIS-C in the respective row relative to the referent group within that category. Associations were adjusted for age group (0-5 years, 6-12 years, 13-20 years), race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic of any race, other non-Hispanic), sex, 1 or more vs no underlying medical conditions, and US Census region (Northeast, South, Midwest, West). ^dOther non-Hispanic race/ethnicity, which included patients documented as having other, unknown, or mixed race, not shown in the table.

Figure 3.. Clinical Outcomes by Day of Hospitalization for Patients With MIS-C and Severe COVID-19

A, Graph shows mechanical ventilator support and death among patients with MIS-C (n = 529 with respiratory support data available) and patients with severe acute COVID-19 (n = 563 with respiratory support data available). B, Graph shows vasopressor support and death among patients with MIS-C (n = 528 with vasopressor support data available) and patients with severe acute COVID-19 (n = 565 with vasopressor support data available). Percentages receiving mechanical ventilator or vasopressor support by day of admission use the full denominators specified at day 1 (the initial day of hospitalization). Some patients had missing information on mechanical ventilator or vasopressor use and are excluded. Tables below the x-axis present the number of patients with MIS-C and COVID-19 still hospitalized by admission day, the number on mechanical ventilation or receiving vasopressor support, and the cumulative deaths during index hospitalization. Cardiovascular pediatric Severe Organ Failure Assessment (pSOFA) scores range from 0 to 4 and were documented daily through 7 days, twice weekly through day 22, then at day 28. Details of pSOFA score criteria are included in eTable 2 in the Supplement. Scores of 2 to 4, indicating vasopressor use, are presented in the figure. COVID-19 indicates coronavirus disease 2019; MIS-C, multisystem inflammatory syndrome in children.

Figure 4.. Cardiovascular Outcomes of Patients With MIS-C^a

A. Graph shows resolution of decreased left ventricular ejection fraction (EF) on echocardiogram with mild (EF, 45% to <55%), moderate (EF, 35% to <45%), and severe (EF<35%) impairment with days to normalization (EF ≥55%). B, Graph shows resolution of coronary artery aneurysms defined as z score ≥2.5 for left anterior descending or right coronary artery. Patients were evaluated from the day of first echocardiographic evaluation and censored on the day when repeat echocardiograph showed recovery or on the day of their last repeat echocardiogram if they had not recovered through 40 days. IQR indicates interquartile range and MIS-C, multisystem inflammatory syndrome in children. ^aKaplan-Meier curves shown up to 40 days from admission given early resolution of cardiac dysfunction in most patients with few uncensored by 40 days. Five patients were censored before documented resolution of reduced left ventricular EF at a median time of 2 days (range, 0-8 days); all other patients had resolution documented by 142 days. Nine patients were censored before documented resolution of coronary artery aneurysms at a median time of 4 days (range, 0-30 days); all other patients had resolution documented by 76 days.