Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome

Неврологические проявления у детей и подростков, госпитализированных в США по поводу COVID-19 или мультисистемного воспалительного синдрома
Emily R. Levy, Mary Beth F. Son, Joseph A. Carcillo, Mary Allen Staat, Ericka L. Fink, Melania M. Bembea, Christopher L. Carroll, Heidi R. Flori, Aline B. Maddux, Adrienne G. Randolph, Courtney M. Rowan, Lincoln Smith, Neal J. Thomas, Kelly N. Michelson, Philip C. Spinella, Ryan W. Carroll, Jane W. Newburger, Tina Young Poussaint, Natasha Halasa, Vicki Montgomery, Manish M. Patel, Michele Kong, Peter M. Mourani, Adam J. Ratner, Jill M. Cholette, Julie C. Fitzgerald, Simon Li, Stephanie P. Schwartz, Mark W. Tenforde, Leora R. Feldstein, Ilana Harwayne‐Gidansky, Kerri L. LaRovere, Becky J. Riggs, Cameron C. Young, Margaret M. Newhams, Mia Maamari, Tracie C. Walker, Aalok R. Singh, Heda Dapul, Charlotte V. Hobbs, Gwenn E. McLaughlin, Katharine N. Clouser, John K. McGuire, Shira J. Gertz, Steven L. Shein, Álvaro Coronado Muñoz, Katherine Irby, John S. Giuliano, Mark W. Hall, Jennifer E. Schuster, Sule Doymaz, Laura L. Loftis, Keiko M. Tarquinio, Christopher Babbitt, Ryan A. Nofziger, Lawrence C. Kleinman, Michael Keenaghan, Natalie Z. Cvijanovich, Janet R. Hume, Kari Wellnitz, Elizabeth H. Mack, Overcoming COVID-19 Investigators, First Name and Middle Initial Last Name, Mary Glas Gaspers, Katri Typpo, Ronald C. Sanders, Adam J. Schwarz, Helen Harvey, Matt S. Zinter, Bria M. Coates, Guru Bhoojhawon, Kevin Havlin, Janice E Sullivan, Tamara T. Bradford, Susan V. Lipton, Ana Lía Graciano, Sabrina Chen, Suden Kücükak, Neil D. Fernandes, Phoebe H. Yager, Kimberly L Marohn, Sabrina M. Heidemann, Melissa L. Cullimore, Russell J. McCulloh, Steven M. Horwitz, Rowan Walsh, Vijaya L Soma, Jennifer Gillen, Sheemon Zackai, Kate G. Ackerman, Saul Hymes, Philip Overby, Amanda Lansell, Monica L. Koncicki, Dai Kimura, Cindy Bowens, Hillary Crandall, Pelin Cengiz
2021-03-05

COVID-19multisystem inflammatory syndrome in childrenneurologic involvementsevere encephalopathystroke
Importance: Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. Objective: To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. Setting, Design, and Participants: 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. Exposures: Severe acute respiratory syndrome coronavirus 2. Main Outcomes and Measures: Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. Results: 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. Conclusions and Relevance: 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.
1
Among 1,695 hospitalized US patients younger than 21 years with COVID-19 or multisystem inflammatory syndrome, 365 (22%) had documented neurologic involvement.
2
Life-threatening manifestations included severe encephalopathy, sometimes with splenial lesions, and stroke; the abstract reports 15 severe encephalopathy cases and 12 strokes.
3
Most affected patients (322 of 365; 88%) had transient neurologic symptoms and survived, while 43 (12%) developed life-threatening neurologic conditions attributed to COVID-19.
4
Neurologic involvement was associated with preexisting neurologic disorders, present in 22% of affected patients versus 8% without neurologic involvement; however, 53% of affected patients were previously healthy.
5
The findings demonstrate a broad spectrum of neurologic involvement in hospitalized children and adolescents with COVID-19 or multisystem inflammatory syndrome, ranging from transient symptoms to severe disease.

Children and adolescents hospitalized in the United States with COVID-19 or multisystem inflammatory syndrome in children

The spectrum, severity, and outcomes of neurologic involvement associated with COVID-19, including transient symptoms and life-threatening neurologic conditions

Publication Details
Publication Date
2021-03-05
Journal
Publisher
ISSN
Cited by
406
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Author Information
Authors
Emily R. Levy
Mary Beth F. Son
Joseph A. Carcillo
Mary Allen Staat
Ericka L. Fink
Melania M. Bembea
Christopher L. Carroll
Heidi R. Flori
Aline B. Maddux
Adrienne G. Randolph
Courtney M. Rowan
Lincoln Smith
Neal J. Thomas
Kelly N. Michelson
Philip C. Spinella
Ryan W. Carroll
Jane W. Newburger
Tina Young Poussaint
Natasha Halasa
Vicki Montgomery
Manish M. Patel
Michele Kong
Peter M. Mourani
Adam J. Ratner
Jill M. Cholette
Julie C. Fitzgerald
Simon Li
Stephanie P. Schwartz
Mark W. Tenforde
Leora R. Feldstein
Ilana Harwayne‐Gidansky
Kerri L. LaRovere
Becky J. Riggs
Cameron C. Young
Margaret M. Newhams
Mia Maamari
Tracie C. Walker
Aalok R. Singh
Heda Dapul
Charlotte V. Hobbs
Gwenn E. McLaughlin
Katharine N. Clouser
John K. McGuire
Shira J. Gertz
Steven L. Shein
Álvaro Coronado Muñoz
Katherine Irby
John S. Giuliano
Mark W. Hall
Jennifer E. Schuster
Sule Doymaz
Laura L. Loftis
Keiko M. Tarquinio
Christopher Babbitt
Ryan A. Nofziger
Lawrence C. Kleinman
Michael Keenaghan
Natalie Z. Cvijanovich
Janet R. Hume
Kari Wellnitz
Elizabeth H. Mack
Overcoming COVID-19 Investigators
First Name and Middle Initial Last Name
Mary Glas Gaspers
Katri Typpo
Ronald C. Sanders
Adam J. Schwarz
Helen Harvey
Matt S. Zinter
Bria M. Coates
Guru Bhoojhawon
Kevin Havlin
Janice E Sullivan
Tamara T. Bradford
Susan V. Lipton
Ana Lía Graciano
Sabrina Chen
Suden Kücükak
Neil D. Fernandes
Phoebe H. Yager
Kimberly L Marohn
Sabrina M. Heidemann
Melissa L. Cullimore
Russell J. McCulloh
Steven M. Horwitz
Rowan Walsh
Vijaya L Soma
Jennifer Gillen
Sheemon Zackai
Kate G. Ackerman
Saul Hymes
Philip Overby
Amanda Lansell
Monica L. Koncicki
Dai Kimura
Cindy Bowens
Hillary Crandall
Pelin Cengiz
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