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

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To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  How do the characteristics and outcomes of children and adolescents with multisystem inflammatory syndrome in children (MIS-C) compare with severe coronavirus disease 2019 (COVID-19)?

Findings  In this case series that included 539 patients with MIS-C and 577 patients with severe COVID-19, patients with MIS-C were more likely than those with severe COVID-19 to be 6 to 12 years old, be non-Hispanic Black, and have severe cardiovascular or mucocutaneous involvement and more extreme inflammation.

Meaning  The study findings suggest patterns of clinical presentation and organ involvement that distinguish between patients with MIS-C and 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.

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Article Information

Corresponding Author: Adrienne G. Randolph, MD, Boston Children’s Hospital, 300 Longwood Ave, Bader 634, Boston, MA 02115 (adrienne.randolph@childrens.harvard.edu).

Accepted for Publication: February 8, 2021.

Published Online: February 24, 2021. doi:10.1001/jama.2021.2091

Author Contributions: Dr Patel had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Feldstein, Tenforde, and Friedman contributed equally, as did Drs Patel, Newburger, and Randolph.

Concept and design: Feldstein, Li, Walker, Hobbs, Halasa, Doymaz, Horwitz, Patel, Randolph.

Acquisition, analysis, or interpretation of data: Feldstein, Tenforde, Friedman, Newhams, Rose, Dapul, Soma, Maddux, Mourani, Bowens, Maamari, Hall, Riggs, Giuliano, Singh, Li, Kong, Schuster, McLaughlin, Schwartz, Loftis, Hobbs, Halasa, Babbitt, Hume, Gertz, Irby, Clouser, Cvijanovich, Bradford, Smith, Heidemann, Zackai, Wellnitz, Nofziger, Horwitz, Carroll, Rowan, Tarquinio, Mack, Fitzgerald, Coates, Jackson, Young, Son, Patel, Newburger, Randolph.

Drafting of the manuscript: Feldstein, Tenforde, Friedman, Rose, Doymaz, Jackson, Young, Patel, Newburger, Randolph.

Critical revision of the manuscript for important intellectual content: Feldstein, Tenforde, Friedman, Newhams, Dapul, Soma, Maddux, Mourani, Bowens, Maamari, Hall, Riggs, Giuliano, Singh, Li, Kong, Schuster, McLaughlin, Schwartz, Walker, Loftis, Hobbs, Halasa, Doymaz, Babbitt, Hume, Gertz, Irby, Clouser, Cvijanovich, Bradford, Smith, Heidemann, Zackai, Wellnitz, Nofziger, Horwitz, Carroll, Rowan, Tarquinio, Mack, Fitzgerald, Coates, Son, Patel, Newburger, Randolph.

Statistical analysis: Feldstein, Tenforde, Rose, Giuliano, Zackai, Jackson, Young, Randolph.

Obtained funding: Patel, Randolph.

Administrative, technical, or material support: Feldstein, Tenforde, Newhams, Rose, Dapul, Maamari, Hall, Riggs, Kong, McLaughlin, Schwartz, Loftis, Hobbs, Doymaz, Babbitt, Hume, Gertz, Irby, Bradford, Zackai, Wellnitz, Carroll, Fitzgerald, Coates, Son, Randolph.

Supervision: Feldstein, Friedman, Newhams, Singh, Hobbs, Cvijanovich, Horwitz, Carroll, Coates, Patel, Randolph.

Conflict of Interest Disclosures: Dr Maddux reported receiving grants from National Institutes of Health (NIH) (K23HD096018) and Francis Family Foundation (Parker B. Francis Fellowship) during the conduct of the study. Dr Mourani reported receiving grants from the NIH. Dr Hall reported receiving personal fees from LaJolla Pharmaceuticals for service on a data safety and monitoring board outside the submitted work. Dr Schuster reported receiving grants from Merck outside the submitted work. Dr Halasa reported receiving grants from Sanofi, Quindell, and Quidel; personal fees from Genentech (educational grant); and hemagglutination inhibition and microneutralization testing and vaccine donation from Sanofi outside the submitted work. Dr Cvijanovich reported receiving grants from Cincinnati Children’s Hospital Medical Center outside the submitted work. Dr Rowan reported receiving grants from the National Heart, Lung, and Blood Institute (K23HL150244-01A1) outside the submitted work. Dr Fitzgerald reported receiving grants from an NIH career development award outside the submitted work. Dr Newburger reported serving as chair of events adjudication committee for a trial on apixaban in children for Pfizer and Bristol-Myers Squibb, as chair of events adjudication committee for a trial of Entresto in children for Novartis, and as a steering committee member for a trial of endoxaban for Daiichi-Sankyo outside the submitted work. Dr Randolph reported receiving royalties from UpToDate and personal fees from LaJolla Pharma Inc outside the submitted work. No other disclosures were reported.

Funding/Support: This study was funded by the Centers for Disease Control and Prevention (CDC) under a contract to Boston Children’s Hospital.

Role of the Funder/Sponsor: The CDC designed and conducted the study; collected, managed, analyzed, and interpreted the data; prepared, reviewed, and approved the manuscript; and had a role in the decision to submit the manuscript for publication and journal choice, and had the right to veto publication.

Group Information: The Overcoming COVID-19 Investigators are listed in the eAppendix in the Supplement.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC.

Additional Contributions: We appreciate and thank the many research coordinators at the Overcoming COVID-19 hospitals who assisted in data collection for this study. We thank the leadership of the Pediatric Acute Lung Injury and Sepsis Investigator’s (PALISI) Network for their ongoing support.

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