Data-driven clustering identifies features distinguishing multisystem inflammatory syndrome from acute COVID-19 in children and adolescents

Alon Geva; Manish S Patel; Margaret M Newhams; Cameron C Young; Mary Beth F Son; Michele Kong; Aline B Maddux; Mark W Hall; Becky J Riggs; Aalok R Singh; John S Giuliano; Charlotte V Hobbs; Laura L Loftis; Gwenn E McLaughlin; Stephanie P Schwartz; Jennifer E Schuster; Christopher J Babbitt; Natasha B Halasa; Shira J Gertz; Sule Doymaz; Janet R Hume; Tamara T Bradford; Katherine Irby; Christopher L Carroll; John K McGuire; Keiko M Tarquinio; Courtney M Rowan; Elizabeth H Mack; Natalie Z Cvijanovich; Julie C Fitzgerald; Philip C Spinella; Mary A Staat; Katharine N Clouser; Vijaya L Soma; Heda Dapul; Mia Maamari; Cindy Bowens; Kevin M Havlin; Peter M Mourani; Sabrina M Heidemann; Steven M Horwitz; Leora R Feldstein; Mark W Tenforde; Jane W Newburger; Kenneth D Mandl; Adrienne G Randolph

doi:10.1016/j.eclinm.2021.101112

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Data-driven clustering identifies features distinguishing multisystem inflammatory syndrome from acute COVID-19 in children and adolescents

Journal article

Open access

Peer reviewed

Data-driven clustering identifies features distinguishing multisystem inflammatory syndrome from acute COVID-19 in children and adolescents

Alon Geva, Manish S Patel, Margaret M Newhams, Cameron C Young, Mary Beth F Son, Michele Kong, Aline B Maddux, Mark W Hall, Becky J Riggs, Aalok R Singh, …

EClinicalMedicine, Vol.40, pp.101112-101112

10/01/2021

DOI: https://doi.org/10.1016/j.eclinm.2021.101112

PMID: 34485878

Abstract

Clustering

COVID-19

Critical care medicine

Multisystem inflammatory syndrome

Pediatrics

Multisystem inflammatory syndrome in children (MIS-C) consensus criteria were designed for maximal sensitivity and therefore capture patients with acute COVID-19 pneumonia. We performed unsupervised clustering on data from 1,526 patients (684 labeled MIS-C by clinicians) <21 years old hospitalized with COVID-19-related illness admitted between 15 March 2020 and 31 December 2020. We compared prevalence of assigned MIS-C labels and clinical features among clusters, followed by recursive feature elimination to identify characteristics of potentially misclassified MIS-C-labeled patients. Of 94 clinical features tested, 46 were retained for clustering. Cluster 1 patients (N = 498; 92% labeled MIS-C) were mostly previously healthy (71%), with mean age 7·2 ± 0·4 years, predominant cardiovascular (77%) and/or mucocutaneous (82%) involvement, high inflammatory biomarkers, and mostly SARS-CoV-2 PCR negative (60%). Cluster 2 patients (N = 445; 27% labeled MIS-C) frequently had pre-existing conditions (79%, with 39% respiratory), were similarly 7·4 ± 2·1 years old, and commonly had chest radiograph infiltrates (79%) and positive PCR testing (90%). Cluster 3 patients (N = 583; 19% labeled MIS-C) were younger (2·8 ± 2·0 y), PCR positive (86%), with less inflammation. Radiographic findings of pulmonary infiltrates and positive SARS-CoV-2 PCR accurately distinguished cluster 2 MIS-C labeled patients from cluster 1 patients. Using a data driven, unsupervised approach, we identified features that cluster patients into a group with high likelihood of having MIS-C. Other features identified a cluster of patients more likely to have acute severe COVID-19 pulmonary disease, and patients in this cluster labeled by clinicians as MIS-C may be misclassified. These data driven phenotypes may help refine the diagnosis of MIS-C.

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Title: Subtitle: Data-driven clustering identifies features distinguishing multisystem inflammatory syndrome from acute COVID-19 in children and adolescents
Creators: Alon Geva
Manish S Patel - COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, GA, USA
Margaret M Newhams
Cameron C Young
Mary Beth F Son
Michele Kong
Aline B Maddux
Mark W Hall
Becky J Riggs
Aalok R Singh
John S Giuliano
Charlotte V Hobbs
Laura L Loftis
Gwenn E McLaughlin
Stephanie P Schwartz
Jennifer E Schuster
Christopher J Babbitt
Natasha B Halasa
Shira J Gertz
Sule Doymaz
Janet R Hume - Division of Pediatric Critical Care, University of Minnesota Masonic Children's Hospital, Minneapolis, MN, USA
Tamara T Bradford - Department of Pediatrics, Division of Cardiology, Louisiana State University Health Sciences Center and Children's Hospital of New Orleans, New Orleans, LA, USA
Katherine Irby - Section of Pediatric Critical Care, Department of Pediatrics, Arkansas Children's Hospital, Little Rock, AR, USA
Christopher L Carroll - Division of Critical Care, Connecticut Children's, Hartford, CT, USA
John K McGuire - Division of Pediatric Critical Care Medicine, Department of Pediatrics, Seattle Children's Hospital and the University of Washington, Seattle, WA, USA
Keiko M Tarquinio - Division of Critical Care Medicine, Department of Pediatrics, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, GA, USA
Courtney M Rowan - Division of Pediatric Critical Care Medicine, Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, IN, USA
Elizabeth H Mack - Division of Pediatric Critical Care Medicine, Medical University of South Carolina, Charleston, SC, USA
Natalie Z Cvijanovich - Division of Critical Care Medicine, UCSF Benioff Children's Hospital Oakland, CA, USA
Julie C Fitzgerald - Division of Critical Care, Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
Philip C Spinella - Division of Critical Care, Department of Pediatrics, Washington University School of Medicine in St Louis, St Louis, MO, USA
Mary A Staat - Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
Katharine N Clouser - Department of Pediatrics, Hackensack Meridian School of Medicine, Hackensack, NJ, USA
Vijaya L Soma - Department of Pediatrics, Division of Infectious Diseases, New York University Grossman School of Medicine and Hassenfeld Children's Hospital, New York, NY, USA
Heda Dapul - Division of Pediatric Critical Care Medicine, Department of Pediatrics, New York University Grossman School of Medicine and Hassenfeld Children's Hospital, New York, NY, USA
Mia Maamari - Department of Pediatrics, Division of Critical Care Medicine, University of Texas Southwestern, Children's Health Medical Center Dallas, TX, USA
Cindy Bowens - Department of Pediatrics, Division of Pediatric Critical Care Medicine, University of Louisville, and Norton Children's Hospital, Louisville, KY, USA
Kevin M Havlin - Department of Pediatrics, Division of Pediatric Critical Care Medicine, Central Michigan University, Detroit, MI, USA
Peter M Mourani - Department of Pediatrics, Section of Critical Care Medicine, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA
Sabrina M Heidemann - Department of Pediatrics, Division of Pediatric Critical Care Medicine, Central Michigan University, Detroit, MI, USA
Steven M Horwitz (Author)
Leora R Feldstein - COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, GA, USA
Mark W Tenforde - COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, GA, USA
Jane W Newburger - Department of Cardiology, Boston Children's Hospital, Boston, MA, USA
Kenneth D Mandl - Computational Health Informatics Program, Boston Children's Hospital, Boston, MA
Adrienne G Randolph
Publication Details: EClinicalMedicine, Vol.40, pp.101112-101112
Date published: 10/01/2021
Publisher: Elsevier Ltd
Academic Unit: Medicine - General Internal Medicine (RWJMS); Pediatrics - Critical Care (RWJMS)
Language: English
Resource Type: Journal article
Identifiers: 991031679546504646