Leora R Feldstein1,2, Mark W Tenforde1, Kevin G Friedman3, Margaret Newhams4, Erica Billig Rose1,2, Heda Dapul5, Vijaya L Soma6, Aline B Maddux7, Peter M Mourani7, Cindy Bowens8, Mia Maamari8, Mark W Hall9, Becky J Riggs10, John S Giuliano11, Aalok R Singh12, Simon Li13, Michele Kong14, Jennifer E Schuster15, Gwenn E McLaughlin16, Stephanie P Schwartz17, Tracie C Walker17, Laura L Loftis18, Charlotte V Hobbs19, Natasha B Halasa20, Sule Doymaz21, Christopher J Babbitt22, Janet R Hume23, Shira J Gertz24, Katherine Irby25, Katharine N Clouser26, Natalie Z Cvijanovich27, Tamara T Bradford28, Lincoln S Smith29, Sabrina M Heidemann30, Sheemon P Zackai31, Kari Wellnitz32, Ryan A Nofziger33, Steven M Horwitz34, Ryan W Carroll35, Courtney M Rowan36, Keiko M Tarquinio37, Elizabeth H Mack38, Julie C Fitzgerald39, Bria M Coates40, Ashley M Jackson1, Cameron C Young4, Mary Beth F Son41, Manish M Patel1,2, Jane W Newburger3, Adrienne G Randolph4,42. 1. COVID-19 Response Team, Centers for Disease Control and Prevention, Atlanta, Georgia. 2. Public Health Service Commissioned Corps, Rockville, Maryland. 3. Department of Cardiology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts. 4. Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts. 5. Division of Pediatric Critical Care Medicine, Department of Pediatrics, New York University Grossman School of Medicine, New York. 6. Division of Pediatric Infectious Diseases, Department of Pediatrics, New York University Grossman School of Medicine, New York. 7. Department of Pediatrics, Section of Critical Care Medicine, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora. 8. Division of Critical Care Medicine, Department of Pediatrics, University of Texas Southwestern, Children's Medical Center Dallas, Dallas. 9. Division of Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio. 10. Department of Anesthesiology and Critical Care Medicine, Division of Pediatric Anesthesiology & Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland. 11. Division of Critical Care, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut. 12. Pediatric Critical Care Division, Maria Fareri Children's Hospital at Westchester Medical Center and New York Medical College, Valhalla. 13. Department of Pediatrics, Division of Pediatric Critical Care, Bristol-Myers Squibb Children's Hospital, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey. 14. Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham. 15. Division of Pediatric Infectious Disease, Department of Pediatrics, Children's Mercy Kansas City, Kansas City, Missouri. 16. Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida. 17. Department of Pediatrics, University of North Carolina at Chapel Hill Children's Hospital. 18. Section of Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, Texas. 19. Division of Infectious Diseases, Department of Pediatrics, Department of Microbiology, University of Mississippi Medical Center, Jackson. 20. Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee. 21. Division of Pediatric Critical Care, Department of Pediatrics, SUNY Downstate Health Sciences University, Brooklyn, New York. 22. Division of Pediatric Critical Care, Miller Children's and Women's Hospital of Long Beach, Long Beach, California. 23. Division of Pediatric Critical Care, University of Minnesota Masonic Children's Hospital, Minneapolis. 24. Division of Pediatric Critical Care, Department of Pediatrics, Saint Barnabas Medical Center, Livingston, New Jersey. 25. Section of Pediatric Critical Care, Department of Pediatrics, Arkansas Children's Hospital, Little Rock. 26. Division of Hospital Medicine, Department of Pediatrics, Hackensack University Medical Center, Hackensack, New Jersey. 27. Division of Critical Care Medicine, UCSF Benioff Children's Hospital Oakland, Oakland, California. 28. Division of Cardiology, Department of Pediatrics, Louisiana State University Health Sciences Center and Children's Hospital of New Orleans, New Orleans. 29. Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Washington, Seattle. 30. Division of Pediatric Critical Care Medicine, Department of Pediatrics, Central Michigan University, Detroit. 31. Pediatric Critical Care Medicine, Department of Pediatrics, Icahn School of Medicine at the Mount Sinai Kravis Children's Hospital, New York, New York. 32. Division of Pediatric Critical Care, Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City. 33. Division of Critical Care Medicine, Department of Pediatrics, Akron Children's Hospital, Akron, Ohio. 34. Department of Pediatrics, Division of Critical Care, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey. 35. Division of Pediatric Critical Care Medicine, MassGeneral Hospital for Children, Harvard Medical School, Boston, Massachusetts. 36. Division of Pediatric Critical Care Medicine, Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis. 37. Division of Critical Care Medicine, Department of Pediatrics, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia. 38. Division of Pediatric Critical Care Medicine, Medical University of South Carolina, Charleston. 39. Division of Critical Care, Department of Anesthesiology and Critical Care, The University of Pennsylvania Perelman School of Medicine, Philadelphia. 40. Division of Critical Care Medicine, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois. 41. Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts. 42. Departments of Anesthesia and Pediatrics, Harvard Medical School, Boston, Massachusetts.
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.
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-19died 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.