Neurologic involvement in children and adolescents hospitalized in the United States for COVID-19 or multisystem inflammatory syndrome

Steven M Horwitz; Kerri L LaRovere; Becky J Riggs; Tina Y Poussaint; Cameron C Young; Margaret M Newhams; Mia Maamari; Tracie C Walker; Aalok R Singh; Heda Dapul; Charlotte V Hobbs; Gwenn E McLaughlin; Mary Beth F Son; Aline B Maddux; Katharine N Clouser; Courtney M Rowan; John K McGuire; Julie C Fitzgerald; Shira J Gertz; Steven L Shein; Alvaro Coronado Munoz; Neal J Thomas; Katherine Irby; Emily R Levy; Mary A Staat; Mark W Tenforde; Leora R Feldstein; Natasha B Halasa; John S Giuliano, Jr; Mark W Hall; Michele Kong; Christopher L Carroll; Jennifer E Schuster; Sule Doymaz; Laura L Loftis; Keiko M Tarquinio; Christopher J Babbitt; Ryan A Nofziger; Lawrence Kleinman; Michael A Keenaghan; Natalie Z Cvijanovich; Philip C Spinella; Janet R Hume; Kari Wellnitz; Elizabeth H Mack; Kelly N Michelson; Heidi R Flori; Manish S Patel; Adrienne G Randolph

doi:10.1001/jamaneurol.2021.0504

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Neurologic involvement in children and adolescents hospitalized in the United States for COVID-19 or multisystem inflammatory syndrome

Journal article

Peer reviewed

Neurologic involvement in children and adolescents hospitalized in the United States for COVID-19 or multisystem inflammatory syndrome

Steven M Horwitz, Kerri L LaRovere, Becky J Riggs, Tina Y Poussaint, Cameron C Young, Margaret M Newhams, Mia Maamari, Tracie C Walker, Aalok R Singh, Heda Dapul, …

JAMA neurology, Vol.78(5), pp.536-547

05/01/2021

DOI: https://doi.org/10.1001/jamaneurol.2021.0504

PMID: 33666649

Abstract

Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. Severe acute respiratory syndrome coronavirus 2. Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19-related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown.

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Title: Neurologic involvement in children and adolescents hospitalized in the United States for COVID-19 or multisystem inflammatory syndrome
Creators: Steven M Horwitz (Collaborator)
Kerri L LaRovere - Department of Neurology, Boston Children's Hospital, Boston, Massachusetts
Becky J Riggs - Division of Pediatric Anesthesiology and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
Tina Y Poussaint - Department of Radiology, Boston Children's Hospital, Boston, Massachusetts
Cameron C Young - Division of Critical Care Medicine, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts
Margaret M Newhams - Division of Critical Care Medicine, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts
Mia Maamari - Division of Critical Care Medicine, Department of Pediatrics, University of Texas Southwestern, Children's Health Medical Center Dallas
Tracie C Walker - Department of Pediatrics, University of North Carolina at Chapel Hill Children's Hospital, Chapel Hill
Aalok R Singh - Pediatric Critical Care Division, Maria Fareri Children's Hospital at Westchester Medical Center and New York Medical College, Valhalla
Heda Dapul - Division of Pediatric Critical Care Medicine, Department of Pediatrics, New York University Grossman School of Medicine, New York
Charlotte V Hobbs - Division of Infectious Diseases, Department of Pediatrics, Department of Microbiology, University of Mississippi Medical Center, Jackson
Gwenn E McLaughlin - Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida
Mary Beth F Son - Division of Immunology, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts
Aline B Maddux - Section of Critical Care Medicine, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora
Katharine N Clouser - Department of Pediatrics, Joseph M. Sanzari Children's Hospital at Hackensack University Medical Center, Hackensack, New Jersey
Courtney M Rowan - Division of Pediatric Critical Care Medicine, Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis
John K McGuire - Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Washington, Seattle
Julie C Fitzgerald - Division of Critical Care, Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia
Shira J Gertz - Division of Pediatric Critical Care, Department of Pediatrics, Saint Barnabas Medical Center, Livingston, New Jersey
Steven L Shein - Division of Pediatric Critical Care Medicine, Rainbow Babies and Children's Hospital, Cleveland, Ohio
Alvaro Coronado Munoz - Pediatric Critical Care Division, Department of Pediatrics, University of Texas Health Science Center at Houston, Houston
Neal J Thomas - Department of Pediatrics, Penn State Hershey Children's Hospital, Pennsylvania State University College of Medicine, Hershey
Katherine Irby - Section of Pediatric Critical Care, Department of Pediatrics, Arkansas Children's Hospital, Little Rock
Emily R Levy - Divisions of Pediatric Infectious Diseases and Pediatric Critical Care Medicine, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota
Mary A Staat - Department of Pediatrics, University of Cincinnati, Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
Mark W Tenforde - Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia
Leora R Feldstein - Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia
Natasha B Halasa - Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee
John S Giuliano, Jr - Division of Critical Care, Yale University School of Medicine, New Haven, Connecticut
Mark W Hall - Division of Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio
Michele Kong - Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham
Christopher L Carroll - Division of Critical Care, Connecticut Children's, Hartford, Connecticut
Jennifer E Schuster - Division of Pediatric Infectious Diseases, Department of Pediatrics, Children's Mercy Kansas City, Kansas City, Missouri
Sule Doymaz - Division of Pediatric Critical Care, Department of Pediatrics, State University of New York Downstate Health Sciences University, Brooklyn
Laura L Loftis - Section of Critical Care Medicine, Department of Pediatrics, Texas Children's Hospital, Houston
Keiko M Tarquinio - Division of Critical Care Medicine, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
Christopher J Babbitt - Miller Children's and Women's Hospital of Long Beach, Long Beach, California
Ryan A Nofziger - Division of Critical Care Medicine, Akron Children's Hospital, Akron, Ohio
Lawrence Kleinman - Division of Population Health, Quality, and Implementation Sciences (PopQuIS), Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
Michael A Keenaghan - Pediatric Critical Care, New York City Health and Hospitals, Kings County Hospital, Brooklyn, New York
Natalie Z Cvijanovich - Division of Critical Care Medicine, University of California, San Francisco, Benioff Children's Hospital, Oakland
Philip C Spinella - Division of Critical Care, Department of Pediatrics, Washington University School of Medicine in St Louis, St Louis, Missouri
Janet R Hume - Division of Pediatric Critical Care, University of Minnesota Masonic Children's Hospital, Minneapolis
Kari Wellnitz - Division of Pediatric Critical Care, Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa
Elizabeth H Mack - Division of Pediatric Critical Care Medicine, Medical University of South Carolina, Charleston
Kelly N Michelson - Division of Critical Care Medicine, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois
Heidi R Flori - Division of Pediatric Critical Care Medicine, Department of Pediatrics, Mott Children's Hospital and University of Michigan, Ann Arbor
Manish S Patel - Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia
Adrienne G Randolph - Departments of Anaesthesia and Pediatrics, Harvard Medical School, Boston, Massachusetts
Publication Details: JAMA neurology, Vol.78(5), pp.536-547
Date published: 05/01/2021
Academic Unit: Pediatrics - Critical Care (RWJMS); Medicine - General Internal Medicine (RWJMS); Pediatrics - General Pediatrics (RWJMS)
Language: English
Resource Type: Journal article
Identifiers: 991031679546804646