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Prevalence and Risk Factors of Neurologic Manifestations in Hospitalized Children Diagnosed with Acute SARS-CoV-2 or MIS-C - 14/02/22

Doi : 10.1016/j.pediatrneurol.2021.12.010 
Ericka L. Fink, MD, MS a, , Courtney L. Robertson, MD b, Mark S. Wainwright, MD, PhD c, Juan D. Roa, MD, MS d, Marlina E. Lovett, MD e, Casey Stulce, MD f, Mais Yacoub, MD, FAAP g, Renee M. Potera, MD h, Elizabeth Zivick, MD, FAAP i, Adrian Holloway, MD j, Ashish Nagpal, MD k, Kari Wellnitz, MD l, Theresa Czech, MD m, Katelyn M. Even, MD n, Werther Brunow de Carvalho, PhD, FCCS o, Isadora Souza Rodriguez, MD o, Stephanie P. Schwartz, MD p, Tracie C. Walker, MD p, Santiago Campos-Miño, MD, MSc q, Leslie A. Dervan, MD, MS r, Andrew S. Geneslaw, MD, MS s, Taylor B. Sewell, MD, MBA s, Patrice Pryce, MD t, Wendy G. Silver, MD, MA u, Jieru Egeria Lin, MD, PhD u, Wendy S. Vargas, MD u, Alexis Topjian, MD, MSCE v, Alicia M. Alcamo, MD, MPH v, Jennifer L. McGuire, MD, MSCE w, Jesus Angel Domínguez Rojas, MD x, Jaime Tasayco Muñoz, MD x, Sue J. Hong, MD y, William J. Muller, MD, PhD y, Matthew Doerfler, MD y, Cydni N. Williams, MD, MCR z, Kurt Drury, MD aa, Dhristie Bhagat, MD ab, Aaron Nelson, MD, MBS ab, Dana Price, MD ab, Heda Dapul, MD ac, Laura Santos, MD, MS ac, Robert Kahoud, MD ad, Conall Francoeur, MDCM ae, Brian Appavu, MD af, Kristin P. Guilliams, MD, MSCI ag, Shannon C. Agner, MD, PhD ag, Karen H. Walson, MD ah, Lindsey Rasmussen, MD, FAAP ai, Anna Janas, MD, PhD ai, Peter Ferrazzano, MD aj, Raquel Farias-Moeller, MD ak, Kellie C. Snooks, DO al, Chung-Chou H. Chang, PhD am, James Yun, MS am, Michelle E. Schober, MD an
for the

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

a Division of Pediatric Critical Care Medicine, Department of Critical Care Medicine, Pittsburgh, Pennsylvania; Safar Center for Resuscitation Research, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 
b Departments of Anesthesiology and Critical Care Medicine, and Pediatrics of The Johns Hopkins University SOM, Baltimore, Maryland 
c Division of Pediatric Neurology, University of Washington, Seattle Children's Hospital, Seattle, Washington 
d Department of Pediatrics, Universidad Nacional de Colombia and Fundación Universitaria de Ciencias de la Salud, Bogotá, Colombia 
e Division of Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio 
f Department of Pediatrics, University of Chicago, Chicago, Illinois 
g Division of Critical Care, Department of Pediatrics, UMC Children's Hospital, Las Vegas, Nevada 
h Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 
i Division of Pediatric Critical Care Medicine, Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina 
j Division of Critical Care, Department of Pediatrics, University of Maryland Medical Center, Baltimore, Maryland 
k Department of Pediatrics, Section of Critical Care Medicine, Oklahoma Children's Hospital at OU health, Oklahoma University College of Medicine, Oklahoma City, Oklahoma 
l Division of Pediatric Critical Care, Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa 
m Division of Pediatric Neurology, Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa 
n Division of Pediatric Critical Care Medicine, Penn State College of Medicine, Hershey, Pennsylvania 
o Department of Pediatrics, University of São Paulo, São Paulo, Brazil 
p Department of Pediatrics, University of North Carolina at Chapel Hill Hospitals, Chapel Hill, North Carolina 
q Pediatric Intensive Care Unit, Hospital Metropolitano, Quito, Ecuador 
r Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington 
s Division of Pediatric Critical Care and Hospital Medicine, Department of Pediatrics, Columbia University Irving Medical Center, New York, New York 
t Division of Pediatric Critical Care and Hospital Medicine, Department of Pediatrics, Columbia University Irving Medical Center, Morgan Stanley Children's Hospital New York-Presbyterian Hospital, New York, New York 
u Division of Child Neurology, Department of Neurology, Columbia University Irving Medical Center, New York, New York 
v Division of Critical Care Medicine at The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Departments of Anesthesiology and Critical Care Medicine and Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 
w Division of Neurology at The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Departments of Neurology and Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 
x Division of Pediatric Critical Care, Department of Pediatrics, Hospital de Emergencia Villa El Salvador, Lima, Peru 
y Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, Illinois 
z Division of Pediatric Critical Care, Department of Pediatrics Pediatric Critical Care and Neurotrauma Recovery Program Portland, Oregon Health & Science University, Oregon 
aa Division of Pediatric Critical Care, Department of Pediatrics, Oregon Health & Science University, Portland, Oregon 
ab Department of Neurology, NYU Langone Health, New York, New York 
ac Division of Pediatric Critical Care, Department of Pediatrics, Hassenfeld Children's Hospital at NYU Langone Health, New York, New York 
ad Division of Pediatric Critical Care Medicine, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota 
ae Department of Pediatrics, CHU de Québec – Université Laval Research Center, Quebec City, Quebec, Canada 
af Division of Neurology, Barrow Neurological Institute at Phoenix Children's Hospital, University of Arizona, College of Medicine, Phoenix, Arizona 
ag Departments of Neurology, Pediatrics, and Radiology, Washington University in St. Louis, St. Louis, Missouri 
ah Department of Pediatric Critical Care Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia 
ai Pediatric Critical Care Medicine, Lucile Packard Children's Hospital, Stanford University, Stanford, California 
aj Department of Pediatrics, University of Wisconsin, Madison, Wisconsin 
ak Division Child Neurology, Department of Neurology, Medical College of Wisconsin, Children's Wisconsin, Milwaukee, Wisconsin 
al Department of Pediatrics, Medical College of Wisconsin, Children's Wisconsin, Milwaukee, Wisconsin 
am Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 
an Division of Critical Care of the University of Utah, Department of Pediatrics, Salt Lake City, Utah 

Communications should be addressed to: Fink; Division of Pediatric Critical Care Medicine; UPMC Children's Hospital of Pittsburgh; 4401 Penn Avenue, Faculty Pavilion, 2nd floor; Pittsburgh, PA 15224.Division of Pediatric Critical Care MedicineUPMC Children's Hospital of Pittsburgh4401 Penn AvenueFaculty Pavilion, 2nd floorPittsburghPA15224

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Abstract

Background

Our objective was to characterize the frequency, early impact, and risk factors for neurological manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C).

Methods

Multicenter, cross-sectional study of neurological manifestations in children aged <18 years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neurological manifestations was performed.

Results

Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological manifestation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diagnosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P < 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P < 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15; and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00); all P < 0.05.

Conclusions

In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.

Le texte complet de cet article est disponible en PDF.

Keywords : Neurological manifestations, Pediatrics, SARS-CoV-2, Child development


Plan


 Group authorship: Members of “GCS-NeuroCOVID Consortium – Pediatrics”: Marlina E. Lovett, MD, Department of Pediatrics, Division of Critical Care Medicine, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA; Casey Stulce, MD, Department of Pediatrics, University of Chicago, Chicago, Il, USA; Mais Yacoub MD, FAAP, Department of Pediatrics, Division of Critical Care, UMC Children's Hospital, Las Vegas, NV, USA; Renee M. Potera, MD, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA; Elizabeth Zivick, MD, FAAP, Department of Pediatrics, Division of Pediatric Critical Care Medicine, Medical University of South Carolina, Charleston, South Carolina, USA; Adrian Holloway, MD, Department of Pediatrics, Division of Critical Care, University of Maryland Medical Center, Baltimore, Maryland, USA; Ashish Nagpal, MD, Department of Pediatrics, Section of Critical Care Medicine, Oklahoma Children's Hospital at OU health, Oklahoma University College of Medicine, Oklahoma City, OK, USA; Kari Wellnitz, MD, Division of Pediatric Critical Care, Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA; Theresa Czech, MD, Division of Pediatric Neurology, Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA; Katelyn M. Even, MD, Division of Pediatric Critical Care Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA; Werther Brunow de Carvalho, PhD, FCCS, José Albino da Paz, and Isadora Souza Rodriguez, MD, Department of Pediatrics, University of São Paulo, São Paulo, Brazil; Stephanie P. Schwartz, MD and Tracie C. Walker, MD, Department of Pediatrics, University of North Carolina at Chapel Hill Hospitals, Chapel Hill, North Carolina, USA; Santiago Campos-Miño, MD, MSc, Pediatric Intensive Care Unit, Hospital Metropolitano, Quito, Ecuador; Leslie A. Dervan MD, MS, (University of Washington School of Medicine), Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA; Andrew S Geneslaw, MD, MS and Taylor B. Sewell, MD, MBA, Department of Pediatrics, Division of Pediatric Critical Care and Hospital Medicine, Columbia University Irving Medical Center, New York, NY, USA; Patrice Pryce, MD, Department of Pediatrics, Division of Pediatric Critical Care and Hospital Medicine, Columbia University Irving Medical Center, Morgan Stanley Children's Hospital New York-Presbyterian Hospital, New York, NY, USA; Wendy G. Silver, MD, MA, Jieru Egeria Lin, MD, PhD, and Wendy S. Vargas, MD, Department of Neurology, Division of Child Neurology, Columbia University Irving Medical Center, New York, NY, USA; Alexis Topjian, MD, MSCE and Alicia M Alcamo MD, MPH, Division of Critical Care Medicine at The Children's Hospital of Philadelphia, Philadelphia, PA; Departments of Anesthesiology and Critical Care Medicine and Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Jennifer L McGuire MD MSCE, Division of Neurology at The Children's Hospital of Philadelphia, Philadelphia, PA; Departments of Neurology and Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Jesus Angel Domínguez Rojas, MD, and Jaime Tasayco Muñoz, MD, Department of Pediatrics, Division of Pediatric Critical Care, Hospital de Emergencia Villa El Salvador, Lima, Peru; Sue J. Hong, MD; William J. Muller, MD, PhD, and Matthew Doerfler, MD, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Cydni N. Williams, MD, MCR, Department of Pediatrics, Division of Pediatric Critical Care; Pediatric Critical Care and Neurotrauma Recovery Program Portland, Oregon Health & Science University, OR, USA; Kurt Drury, MD, Oregon Health & Science University, Department of Pediatrics, Division of Pediatric Critical Care, Oregon Health & Science University, Portland, OR, USA; Dhristie Bhagat, MD; Aaron Nelson, MD, MBS, and Dana Price, MD, Department of Neurology, NYU Langone Health, New York, NY, USA; Heda Dapul, MD and Laura Santos, MD, MS, Department of Pediatrics, Division of Pediatric Critical Care, Hassenfeld Children's Hospital at NYU Langone Health, New York, NY, USA; Robert Kahoud, MD, Division of Pediatric Critical Care Medicine, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA; Conall Francoeur, MDCM, Department of Pediatrics, CHU de Québec – Université Laval Research Center, Quebec City, Quebec, Canada; Brian Appavu, MD, Division of Neurology, Barrow Neurological Institute at Phoenix Children's Hospital, University of Arizona, College of Medicine, Phoenix, AZ, USA; Kristin P. Guilliams, MD, MSCI, and Shannon C. Agner, MD, PhD, Departments of Neurology, Pediatrics, and Radiology, Washington University in St. Louis, St. Louis, Missouri, USA; Karen H Walson, MD, Department of Pediatric Critical Care Medicine, Children's Healthcare of Atlanta, Atlanta, GA, USA; Lindsey Rasmussen, MD, FAAP, and Anna Janas, MD, PhD, Pediatric Critical Care Medicine, Lucile Packard Children's Hospital, Stanford University, Stanford, CA, USA; Peter Ferrazzano, MD, Department of Pediatrics, University of Wisconsin, Madison, WI, USA ferrazzano@pediatrics.wisc.edu; Raquel Farias-Moeller, MD, Department of Neurology, Division Child Neurology, Medical College of Wisconsin, Children's Wisconsin. Milwaukee, WI, USA; Kellie C. Snooks, DO, Department of Pediatrics, Medical College of Wisconsin, Children's Wisconsin. Milwaukee, WI, USA; Chung-Chou H. Chang, PhD, and James Yun, MS, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA
 Authors and contributors: Drs. Fink, Robertson, Schober, Wainwright, and Roa had full access to all of data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Fink, Schober, and Robertson. Acquisition, analysis, and interpretation of data: Fink, Schober, Robertson, Wainwright, and Roa. Drafting of the manuscript: Fink. Critical revision of the manuscript for important intellectual content: Fink, Schober, Robertson, Wainwright, Roa. Lovett, Stulce, Yacoub, Potera, Zivick, Holloway, Nagpal, Wellnitz, Czech, Even, Brunow de Carvalho, Da Paz, Rodriguez, Schwartz, Walker, Campos- Miño, Dervan, Geneslaw, Sewell, Lin, Pryce, Silver, Vargas, Topjian, Alcamo, McGuire, Dominguez, Rojas, Tasayco-Muñoz, Hong, Muller, Doerfler, Williams, Drury, Bhagat, Nelson, Price, Dapul, Santos, Kahoud, Francoeur, Appavu, Guilliams, Agner, Walson, Rasmussen, Ferrazzano. Statistical analysis: Yun, Chang, Fink. Obtained funding: Fink, Schober, Robertson. Administrative, technical, or material support: Fink. Supervision: Chang, Fink, Schober, Robertson.
 Declaration of Interest: Related funding: This study was in part funded by the Neurocritical Care Society Investing in Clinical Neurocritical Care Research (INCLINE) grant (EF, MS, CR). Unrelated funding: Fink: National Institutes of Health; payment to the institution. Schober: National Institutes of Health; payment to the institution. Robertson: National Institutes of Health and Army Medical Research and Material Command (AMRMC)/Rubicon Biotechnologies grants; both payments to the institution. National Neurotrauma Society Payment to C. Robertson (travel costs for NNS symposium, Pittsburgh 2019). National Neurotrauma Society President, Council Pediatric Neurocritical Care Research Group Executive Committee, Past-Chair (2016-2018). Wainwright: Sage Therapeutics: Member, Clinical Advisory Board; payment to him. Roa: None.
 Role of the funding source: The funder had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.


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