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JAMA network open
06 03, 2024;7 (6): e2414122.

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

Conall Francoeur, Alicia M Alcamo, Courtney L Robertson, Mark S Wainwright, Juan D Roa, Marlina E Lovett, Casey Stulce, Mais Yacoub, Renee M Potera, Elizabeth Zivick, Adrian Holloway, Ashish Nagpal, Kari Wellnitz, Katelyn M Even, Werther Brunow de Carvalho, Isadora S Rodriguez, Stephanie P Schwartz, Tracie C Walker, Santiago Campos-Mi��o, Leslie A Dervan, Andrew S Geneslaw, Taylor B Sewell, Patrice Pryce, Wendy G Silver, Jieru E Lin, Wendy S Vargas, Alexis Topjian, Jennifer L McGuire, Jesus Angel Dom��nguez Rojas, Jaime Tasayco-Mu��oz, Sue J Hong, William J Muller, Matthew Doerfler, Cydni N Williams, Kurt Drury, Dhristie Bhagat, Aaron Nelson, Dana Price, Heda Dapul, Laura Santos, Robert Kahoud, Brian Appavu, Kristin P Guilliams, Shannon C Agner, Karen H Walson, Lindsey Rasmussen, Ria Pal, Anna Janas, Peter Ferrazzano, Raquel Farias-Moeller, Kellie C Snooks, Chung-Chou H Chang, Tom��s Iolster, Jennifer C Erklauer, Facundo Jorro Baron, Evangeline Wassmer, Michael Yoong, Michelle Jardine, Zoha Mohammad, Akash Deep, Tanil Kendirli, Karen Lidsky, Samantha Dallefeld, Helen Flockton, Shruti Agrawal, Krishna Sumanth Siruguppa, Michaela Waak, Alfonso Guti��rrez-Mata, Warwick Butt, Sixto Bogantes-Ledezma, Fabricio Sevilla-Acosta, Andres Uma��a-Calder��n, Adriana Ulate-Campos, Adriana Yock-Corrales, Victor Brodzik Talisa, Hari Krishnan Kanthimathinathan, Michelle E Schober, Ericka L Fink, Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID) Investigators
Author Information
  1. Conall Francoeur: Division of Pediatric Critical Care Medicine, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada.
  2. Alicia M Alcamo: Division of Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
  3. Courtney L Robertson: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  4. Mark S Wainwright: Division of Pediatric Neurology, University of Washington, Seattle Children's Hospital, Seattle.
  5. Juan D Roa: Department of Pediatrics, Universidad Nacional de Colombia, Bogot��, Colombia.
  6. Marlina E Lovett: Division of Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus.
  7. Casey Stulce: Department of Pediatrics, The University of Chicago, Chicago, Illinois.
  8. Mais Yacoub: Division of Critical Care, Department of Pediatrics, University Medical Center Children's Hospital, Las Vegas, Nevada.
  9. Renee M Potera: Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas.
  10. Elizabeth Zivick: Division of Pediatric Critical Care Medicine, Department of Pediatrics, Medical University of South Carolina, Charleston.
  11. Adrian Holloway: Division of Critical Care, Department of Pediatrics, University of Maryland Medical Center, Baltimore.
  12. Ashish Nagpal: 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.
  13. Kari Wellnitz: Division of Pediatric Critical Care, Department of Pediatrics, Carver College of Medicine, University of Iowa Health Care, Iowa City.
  14. Katelyn M Even: Division of Pediatric Critical Care Medicine, Penn State College of Medicine, The Pennsylvania State University, Hershey.
  15. Werther Brunow de Carvalho: Department of Pediatrics, University of S��o Paulo, S��o Paulo, Brazil.
  16. Isadora S Rodriguez: Department of Pediatrics, University of S��o Paulo, S��o Paulo, Brazil.
  17. Stephanie P Schwartz: Department of Pediatrics, University of North Carolina at Chapel Hill Hospitals, Chapel Hill.
  18. Tracie C Walker: Department of Pediatrics, University of North Carolina at Chapel Hill Hospitals, Chapel Hill.
  19. Santiago Campos-Mi��o: Pediatric Intensive Care Unit, Hospital Metropolitano, Quito, Ecuador.
  20. Leslie A Dervan: Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle.
  21. Andrew S Geneslaw: Division of Pediatric Critical Care and Hospital Medicine, Department of Pediatrics, Columbia University Irving Medical Center, New York, New York.
  22. Taylor B Sewell: Division of Pediatric Critical Care and Hospital Medicine, Department of Pediatrics, Columbia University Irving Medical Center, New York, New York.
  23. Patrice Pryce: 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.
  24. Wendy G Silver: Division of Child Neurology, Department of Neurology, Columbia University Irving Medical Center, New York, New York.
  25. Jieru E Lin: Division of Child Neurology, Department of Neurology, Columbia University Irving Medical Center, New York, New York.
  26. Wendy S Vargas: Division of Child Neurology, Department of Neurology, Columbia University Irving Medical Center, New York, New York.
  27. Alexis Topjian: Division of Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
  28. Jennifer L McGuire: Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia.
  29. Jesus Angel Dom��nguez Rojas: Division of Pediatric Critical Care, Department of Pediatrics, Hospital de Emergencia Villa El Salvador, Lima, Peru.
  30. Jaime Tasayco-Mu��oz: Division of Pediatric Critical Care, Department of Pediatrics, Hospital de Emergencia Villa El Salvador, Lima, Peru.
  31. Sue J Hong: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  32. William J Muller: Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
  33. Matthew Doerfler: Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
  34. Cydni N Williams: Pediatric Critical Care and Neurotrauma Recovery Program, Department of Pediatrics, Oregon Health & Science University, Portland.
  35. Kurt Drury: Division of Pediatric Critical Care, Department of Pediatrics, Oregon Health & Science University, Portland.
  36. Dhristie Bhagat: Department of Neurology, New York University Langone Health, New York.
  37. Aaron Nelson: Department of Neurology, New York University Langone Health, New York.
  38. Dana Price: Department of Neurology, New York University Langone Health, New York.
  39. Heda Dapul: Division of Pediatric Critical Care, Department of Pediatrics, Hassenfeld Children's Hospital, New York University Langone Health, New York.
  40. Laura Santos: Division of Pediatric Critical Care, Department of Pediatrics, Hassenfeld Children's Hospital, New York University Langone Health, New York.
  41. Robert Kahoud: Division of Pediatric Critical Care Medicine, Department of Pediatrics and Adolescent Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota.
  42. Brian Appavu: Division of Neurology, Barrow Neurological Institute at Phoenix Children's Hospital, The University of Arizona, College of Medicine, Phoenix.
  43. Kristin P Guilliams: Department of Neurology, Washington University School of Medicine in St Louis, St Louis, Missouri.
  44. Shannon C Agner: Department of Neurology, Washington University School of Medicine in St Louis, St Louis, Missouri.
  45. Karen H Walson: Division of Pediatric Critical Care Medicine, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia.
  46. Lindsey Rasmussen: Division of Pediatric Critical Care Medicine, Department of Pediatrics, Standford University Medicine, Lucile Packard Children's Hospital Stanford, Stanford, California.
  47. Ria Pal: Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
  48. Anna Janas: Division of Pediatric Critical Care Medicine, Department of Pediatrics, Standford University Medicine, Lucile Packard Children's Hospital Stanford, Stanford, California.
  49. Peter Ferrazzano: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison.
  50. Raquel Farias-Moeller: Division of Child Neurology, Department of Neurology, Medical College of Wisconsin, Children's Wisconsin, Milwaukee.
  51. Kellie C Snooks: Department of Pediatrics, Medical College of Wisconsin, Children's Wisconsin, Milwaukee.
  52. Chung-Chou H Chang: Division of Pediatric Critical Care Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
  53. Tom��s Iolster: Department of Pediatrics, Hospital Universitario Austral, Buenos Aires, Argentina.
  54. Jennifer C Erklauer: Division of Pediatric Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston.
  55. Facundo Jorro Baron: Department of Pediatrics, Hospital General de Ni��os Pedro Elizade, Buenos Aires, Argentina.
  56. Evangeline Wassmer: Birmingham Children's Hospital, Birmingham, United Kingdom.
  57. Michael Yoong: Department of Neurology, Royal London Children's Hospital, London, United Kingdom.
  58. Michelle Jardine: Pediatric Critical Care Unit, University Hospital of Wales, Cardiff, United Kingdom.
  59. Zoha Mohammad: Pediatric Intensive Care Unit, University Hospitals Leicester NHS Trust, Leicester, United Kingdom.
  60. Akash Deep: Department of Women and Children's Health, King's College Hospital, London, United Kingdom.
  61. Tanil Kendirli: Department of Pediatric Critical Care Medicine, Ankara University School of Medicine, Ankara, Turkey.
  62. Karen Lidsky: Division of Pediatric Critical Care Medicine, Wolfson Children's Hospital, Jacksonville, Florida.
  63. Samantha Dallefeld: Department of Pediatrics, Dell Children's Hospital, Austin, Texas.
  64. Helen Flockton: Paediatric Critical Care Unit, Oxford University Hospitals, Oxford, United Kingdom.
  65. Shruti Agrawal: Paediatric Intensive Care Unit, Cambridge University Hospitals, Cambridge, United Kingdom.
  66. Krishna Sumanth Siruguppa: Division of Pediatric Critical Care, Department of Pediatrics, University of California, San Francisco.
  67. Michaela Waak: Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia.
  68. Alfonso Guti��rrez-Mata: Department of Pediatric Neurology, Dr. Carlos S��enz Herrera National Children's Hospital, San Jos��, Costa Rica.
  69. Warwick Butt: Department of Critical Care, Melbourne Medical School, The University of Melbourne, The Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia.
  70. Sixto Bogantes-Ledezma: Department of Pediatric Neurology, Dr. Carlos S��enz Herrera National Children's Hospital, San Jos��, Costa Rica.
  71. Fabricio Sevilla-Acosta: Department of Pediatrics, La Anexi��n Hospital, Guanacaste, Costa Rica.
  72. Andres Uma��a-Calder��n: Department of Pediatric Neurology, Dr. Carlos S��enz Herrera National Children's Hospital, San Jos��, Costa Rica.
  73. Adriana Ulate-Campos: Department of Pediatric Neurology, Dr. Carlos S��enz Herrera National Children's Hospital, San Jos��, Costa Rica.
  74. Adriana Yock-Corrales: Department of Emergency Service, Dr. Carlos S��enz Herrera National Children's Hospital, San Jos��, Costa Rica.
  75. Victor Brodzik Talisa: Division of Pediatric Critical Care Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
  76. Hari Krishnan Kanthimathinathan: West Midlands Regional Genetics Laboratory, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, United Kingdom.
  77. Michelle E Schober: Division of Critical Care, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City.
  78. Ericka L Fink: Division of Pediatric Critical Care Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
PMID: 38857050 DOI: 10.1001/jamanetworkopen.2024.14122

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.

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MeSH Term

Humans
COVID-19
Child
Female
Male
Child, Preschool
Hospitalization
Adolescent
Prospective Studies
SARS-CoV-2
Systemic Inflammatory Response Syndrome
Nervous System Diseases
Infant
Severity of Illness Index
Journal Article Multicenter Study Research Support, Non-U.S. Gov't
Article has an altmetric score of 122

Word Cloud

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