Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19
Authors: Leora R. Feldstein, Mark W. Tenforde, Kevin G. Friedman, Margaret Newhams, Erica Billig Rose, Heda Dapul, Vijaya L. Soma, Aline B. Maddux, Peter M. Mourani, Cindy Bowens, Mia Maamari, Mark W. Hall, Becky J. Riggs, John S. Giuliano, Aalok R. Singh, Simon Li, Michele Kong, Jennifer E. Schuster, Gwenn E. McLaughlin, Stephanie P. Schwartz, Tracie C. Walker, Laura L. Loftis, Charlotte V. Hobbs, Natasha B. Halasa, Sule Doymaz, Christopher J. Babbitt, Janet R. Hume, Shira J. Gertz, Katherine Irby, Katharine N. Clouser, Natalie Z. Cvijanovich, Tamara T. Bradford, Lincoln S. Smith, Sabrina M. Heidemann, Sheemon P. Zackai, Kari Wellnitz, Ryan A. Nofziger, Steven M. Horwitz, Ryan W. Carroll, Courtney M. Rowan, Keiko M. Tarquinio, Elizabeth H. Mack, Julie C. Fitzgerald, Bria M. Coates, Ashley M. Jackson, Cameron C. Young, Mary Beth F. Son, Manish M. Patel, Jane W. Newburger, Adrienne G. Randolph
Journal: JAMA (2021)

<h3>Importance</h3> Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. <h3>Objective</h3> To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19). <h3>Setting, Design, and Participants</h3> 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. <h3>Exposure</h3> SARS-CoV-2. <h3>Main Outcomes and Measures</h3> 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. <h3>Results</h3> 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,<i>P</i> &lt; .001), higher C-reactive protein level (median, 152 mg/L vs 33 mg/L;<i>P</i> &lt; .001), and lower platelet count (&lt;150 ×10<sup>3</sup>cells/μL [212/523 {41%} vs 84/486 {17%},<i>P</i> &lt; .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. <h3>Conclusions and Relevance</h3> 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.