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

Leora R. Feldstein, PhD; Mark W. Tenforde, MD; Kevin G. Friedman, MD; Margaret Newhams, MPH; Erica Billig Rose, PhD; Heda Dapul, MD; Vijaya L. Soma, MD; Aline B. Maddux, MD; Peter M. Mourani, MD; Cindy Bowens, MD; Mia Maamari, MD; Mark W. Hall, MD; Becky J. Riggs, MD; John S. Giuliano Jr, MD; Aalok R. Singh, MD; Simon Li, MD; Michele Kong, MD; Jennifer E. Schuster, MD; Gwenn E. McLaughlin, MD; Stephanie P. Schwartz, MD; Tracie C. Walker, MD; Laura L. Loftis, MD; Charlotte V. Hobbs, MD; Natasha B. Halasa, MD; Sule Doymaz, MD; Christopher J. Babbitt, MD; Janet R. Hume, MD; Shira J. Gertz, MD; Katherine Irby, MD; Katharine N. Clouser, MD; Natalie Z. Cvijanovich, MD; Tamara T. Bradford, MD; Lincoln S. Smith, MD; Sabrina M. Heidemann, MD; Sheemon P. Zackai, MD; Kari Wellnitz, MD; Ryan A. Nofziger, MD; Steven M. Horwitz, MD; Ryan W. Carroll, MD; Courtney M. Rowan, MD; Keiko M. Tarquinio, MD; Elizabeth H. Mack, MD; Julie C. Fitzgerald, MD; Bria M. Coates, MD; Ashley M. Jackson, MPH; Cameron C. Young; Mary Beth F. Son, MD; Manish M. Patel, MD; Jane W. Newburger, MD; Adrienne G. Randolph, MD; for the Overcoming COVID-19 Investigators


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

February 24, 2021
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