Severe Pediatric Neurological Manifestations With SARS-CoV-2 or MIS-C Hospitalization and New Morbidity

Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID) Investigators

doi:10.1001/jamanetworkopen.2024.14122

Severe Pediatric Neurological Manifestations With SARS-CoV-2 or MIS-C Hospitalization and New Morbidity

Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID) Investigators

School of Biosciences

Division of Pediatric Critical Care Medicine, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada.
Department of Pediatrics, Division of Nephrology, The Children's Hospital of Philadelphia, University of Pennsylvania, Perelman School of Medicine, 3401 Civic Center Blvd, Philadelphia, PA 19104.
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Division of Pediatric Neurology, University of Washington, Seattle Children's Hospital, Seattle.
Department of Pediatric Neurology, Faculty of Medicine, Fundación Universitaria de Ciencias de la Salud, Bogotá, Colombia.
Division of Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus.
Department of Pediatrics, The University of Chicago, Chicago, Illinois.
Division of Critical Care, Department of Pediatrics, University Medical Center Children's Hospital, Las Vegas, Nevada.
Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas.
Division of Pediatric Critical Care Medicine, Department of Pediatrics, Medical University of South Carolina, Charleston.
Division of Critical Care, Department of Pediatrics, University of Maryland Medical Center, Baltimore.
Department of Pediatrics, Section of Critical Care Medicine, Oklahoma Children's Hospital at Oklahoma University Health, College of Medicine, The University of Oklahoma Health Sciences, Oklahoma City.
Division of Pediatric Critical Care, Department of Pediatrics, Carver College of Medicine, University of Iowa Health Care, Iowa City.
Division of Pediatric Critical Care Medicine, Penn State College of Medicine, The Pennsylvania State University, Hershey.
Department of Pediatrics, University of São Paulo, São Paulo, Brazil.
Department of Pediatrics, University of North Carolina at Chapel Hill Hospitals, Chapel Hill.
Pediatric Intensive Care Unit, Hospital Metropolitano, Quito, Ecuador.
Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle.
Division of Pediatric Critical Care and Hospital Medicine, Department of Pediatrics, Columbia University Irving Medical Center, New York, New York.
Division of Pediatric Critical Care and Hospital Medicine, Department of Pediatrics, Columbia University Irving Medical Center, New York-Presbyterian Morgan Stanley Children's Hospital, New York, New York.
Division of Child Neurology, Department of Neurology, Columbia University Irving Medical Center, New York, New York.
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Division of Pediatric Critical Care, Department of Pediatrics, Hospital de Emergencia Villa El Salvador, Lima, Peru.
Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Division of Pediatric Critical Care, Department of Pediatrics, Oregon Health & Science University, Portland.
Department of Neurology, New York University Langone Health, New York.
Division of Pediatric Critical Care, Department of Pediatrics, Hassenfeld Children's Hospital, New York University Langone Health, New York.
Division of Pediatric Critical Care Medicine, Department of Pediatrics and Adolescent Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota.
Division of Neurology, Barrow Neurological Institute at Phoenix Children's Hospital, The University of Arizona, College of Medicine, Phoenix.
Mallinckrodt Institute of Radiology, Washington University School of Medicine in St Louis, St Louis, Missouri.
Division of Pediatric Critical Care Medicine, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia.
Division of Pediatric Critical Care Medicine, Department of Pediatrics, Standford University Medicine, Lucile Packard Children's Hospital Stanford, Stanford, California.
Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison.

Research output: Contribution to journal › Article › peer-review

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33 Downloads (Pure)

Abstract

Importance: Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. Objective: To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge. Design, Setting, and Participants: This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. Exposure: Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. Main Outcomes and Measures: The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition. Results: Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P <.001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P =.002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P =.001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P =.009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge. Conclusions and Relevance: The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.

Original language	English
Article number	e2414122
Number of pages	15
Journal	JAMA Network Open
Volume	7
Issue number	6
Early online date	10 Jun 2024
DOIs	https://doi.org/10.1001/jamanetworkopen.2024.14122
Publication status	E-pub ahead of print - 10 Jun 2024

Bibliographical note

CC BY

Keywords

Severity of Illness Index
Prospective Studies
Humans
Child, Preschool
Hospitalization - statistics & numerical data
Male
Infant
Systemic Inflammatory Response Syndrome - epidemiology
Nervous System Diseases - etiology - epidemiology
COVID-19 - complications - epidemiology
SARS-CoV-2
Adolescent
Female
Child
COVID-19/complications
Systemic Inflammatory Response Syndrome/epidemiology
Nervous System Diseases/etiology
Hospitalization/statistics & numerical data

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Severe Pediatric Neurological Manifestations With SARS-CoV-2 or MIS-C Hospitalization and New MorbidityLicence: CC BY 4.0

Cite this

@article{b9036febdb414dd5a8d38bac12709da8,

title = "Severe Pediatric Neurological Manifestations With SARS-CoV-2 or MIS-C Hospitalization and New Morbidity",

abstract = "Importance: Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. Objective: To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge. Design, Setting, and Participants: This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. Exposure: Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. Main Outcomes and Measures: The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition. Results: Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3\% male) were included in this study. Most (2980 [83.5\%]) had acute SARS-CoV-2; the remainder (588 [16.5\%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0\%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8\%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7\% [n = 142] vs 14.6\% [n = 356]; P <.001). For survivors with MIS-C, 28.0\% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5\% (n = 68) of those without severe neurological manifestations (P =.002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95\% CI, 1.27-2.70]; P =.001) and those with MIS-C (odds ratio, 2.18 [95\% CI, 1.22-3.89]; P =.009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge. Conclusions and Relevance: The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.",

keywords = "Severity of Illness Index, Prospective Studies, Humans, Child, Preschool, Hospitalization - statistics \& numerical data, Male, Infant, Systemic Inflammatory Response Syndrome - epidemiology, Nervous System Diseases - etiology - epidemiology, COVID-19 - complications - epidemiology, SARS-CoV-2, Adolescent, Female, Child, COVID-19/complications, Systemic Inflammatory Response Syndrome/epidemiology, Nervous System Diseases/etiology, Hospitalization/statistics \& numerical data",

author = "Conall Francoeur and Alcamo, \{Alicia M\} and Robertson, \{Courtney L\} and Wainwright, \{Mark S\} and Roa, \{Juan D\} and Lovett, \{Marlina E\} and Casey Stulce and Mais Yacoub and Potera, \{Renee M\} and Elizabeth Zivick and Adrian Holloway and Ashish Nagpal and Kari Wellnitz and Even, \{Katelyn M\} and \{Brunow de Carvalho\}, Werther and Rodriguez, \{Isadora S\} and Schwartz, \{Stephanie P\} and Walker, \{Tracie C\} and Santiago Campos-Mi{\~n}o and Dervan, \{Leslie A\} and Geneslaw, \{Andrew S\} and Sewell, \{Taylor B\} and Patrice Pryce and Silver, \{Wendy G\} and Lin, \{Jieru E\} and Vargas, \{Wendy S\} and Alexis Topjian and McGuire, \{Jennifer L\} and \{Dom{\'i}nguez Rojas\}, \{Jesus Angel\} and Jaime Tasayco-Mu{\~n}oz and Hong, \{Sue J\} and Muller, \{William J\} and Matthew Doerfler and Williams, \{Cydni N\} and Kurt Drury and Dhristie Bhagat and Aaron Nelson and Dana Price and Heda Dapul and Laura Santos and Robert Kahoud and Brian Appavu and Guilliams, \{Kristin P\} and Agner, \{Shannon C\} and Walson, \{Karen H\} and Lindsey Rasmussen and Ria Pal and Anna Janas and Peter Ferrazzano and Evangeline Wassmer and \{Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID) Investigators\}",

note = "CC BY",

year = "2024",

month = jun,

day = "10",

doi = "10.1001/jamanetworkopen.2024.14122",

language = "English",

volume = "7",

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TY - JOUR

T1 - Severe Pediatric Neurological Manifestations With SARS-CoV-2 or MIS-C Hospitalization and New Morbidity

AU - Francoeur, Conall

AU - Alcamo, Alicia M

AU - Robertson, Courtney L

AU - Wainwright, Mark S

AU - Roa, Juan D

AU - Lovett, Marlina E

AU - Stulce, Casey

AU - Yacoub, Mais

AU - Potera, Renee M

AU - Zivick, Elizabeth

AU - Holloway, Adrian

AU - Nagpal, Ashish

AU - Wellnitz, Kari

AU - Even, Katelyn M

AU - Brunow de Carvalho, Werther

AU - Rodriguez, Isadora S

AU - Schwartz, Stephanie P

AU - Walker, Tracie C

AU - Campos-Miño, Santiago

AU - Dervan, Leslie A

AU - Geneslaw, Andrew S

AU - Sewell, Taylor B

AU - Pryce, Patrice

AU - Silver, Wendy G

AU - Lin, Jieru E

AU - Vargas, Wendy S

AU - Topjian, Alexis

AU - McGuire, Jennifer L

AU - Domínguez Rojas, Jesus Angel

AU - Tasayco-Muñoz, Jaime

AU - Hong, Sue J

AU - Muller, William J

AU - Doerfler, Matthew

AU - Williams, Cydni N

AU - Drury, Kurt

AU - Bhagat, Dhristie

AU - Nelson, Aaron

AU - Price, Dana

AU - Dapul, Heda

AU - Santos, Laura

AU - Kahoud, Robert

AU - Appavu, Brian

AU - Guilliams, Kristin P

AU - Agner, Shannon C

AU - Walson, Karen H

AU - Rasmussen, Lindsey

AU - Pal, Ria

AU - Janas, Anna

AU - Ferrazzano, Peter

AU - Wassmer, Evangeline

AU - Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID) Investigators

N1 - CC BY

PY - 2024/6/10

Y1 - 2024/6/10

N2 - Importance: Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. Objective: To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge. Design, Setting, and Participants: This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. Exposure: Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. Main Outcomes and Measures: The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition. Results: Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P <.001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P =.002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P =.001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P =.009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge. Conclusions and Relevance: The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.

AB - Importance: Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. Objective: To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge. Design, Setting, and Participants: This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. Exposure: Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. Main Outcomes and Measures: The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition. Results: Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P <.001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P =.002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P =.001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P =.009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge. Conclusions and Relevance: The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.

KW - Severity of Illness Index

KW - Prospective Studies

KW - Humans

KW - Child, Preschool

KW - Hospitalization - statistics & numerical data

KW - Male

KW - Infant

KW - Systemic Inflammatory Response Syndrome - epidemiology

KW - Nervous System Diseases - etiology - epidemiology

KW - COVID-19 - complications - epidemiology

KW - SARS-CoV-2

KW - Adolescent

KW - Female

KW - Child

KW - COVID-19/complications

KW - Systemic Inflammatory Response Syndrome/epidemiology

KW - Nervous System Diseases/etiology

KW - Hospitalization/statistics & numerical data

UR - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2819749

UR - https://www.scopus.com/pages/publications/85195628981

U2 - 10.1001/jamanetworkopen.2024.14122

DO - 10.1001/jamanetworkopen.2024.14122

M3 - Article

C2 - 38857050

SN - 2574-3805

VL - 7

JO - JAMA Network Open

JF - JAMA Network Open

IS - 6

M1 - e2414122

ER -

Severe Pediatric Neurological Manifestations With SARS-CoV-2 or MIS-C Hospitalization and New Morbidity

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Keywords

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