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

doi:10.1001/jamanetworkopen.2024.14122

Multicenter Study

. 2024 Jun 3;7(6):e2414122.

doi: 10.1001/jamanetworkopen.2024.14122.

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

Conall Francoeur¹, Alicia M Alcamo^{2

3

4}, Courtney L Robertson⁵, Mark S Wainwright⁶, Juan D Roa^{7

8}, Marlina E Lovett⁹, Casey Stulce¹⁰, Mais Yacoub¹¹, Renee M Potera¹², Elizabeth Zivick¹³, Adrian Holloway¹⁴, Ashish Nagpal¹⁵, Kari Wellnitz¹⁶, Katelyn M Even¹⁷, Werther Brunow de Carvalho¹⁸, Isadora S Rodriguez¹⁸, Stephanie P Schwartz¹⁹, Tracie C Walker¹⁹, Santiago Campos-Miño²⁰, Leslie A Dervan²¹, Andrew S Geneslaw²², Taylor B Sewell²², Patrice Pryce²³, Wendy G Silver²⁴, Jieru E Lin²⁴, Wendy S Vargas²⁴, Alexis Topjian^{2

3

4}, Jennifer L McGuire^{4

25

26}, Jesus Angel Domínguez Rojas²⁷, Jaime Tasayco-Muñoz²⁷, Sue J Hong⁵, William J Muller²⁸, Matthew Doerfler²⁸, Cydni N Williams^{29

30}, Kurt Drury³⁰, Dhristie Bhagat³¹, Aaron Nelson³¹, Dana Price³¹, Heda Dapul³², Laura Santos³², Robert Kahoud³³, Brian Appavu³⁴, Kristin P Guilliams^{35

36

37}, Shannon C Agner^{35

36

37}, Karen H Walson³⁸, Lindsey Rasmussen³⁹, Ria Pal⁴⁰, Anna Janas³⁹, Peter Ferrazzano⁴¹, Raquel Farias-Moeller⁴², Kellie C Snooks⁴³, Chung-Chou H Chang⁴⁴, Tomás Iolster⁴⁵, Jennifer C Erklauer^{46

47}, Facundo Jorro Baron⁴⁸, Evangeline Wassmer^{49

50

51}, Michael Yoong⁵², Michelle Jardine⁵³, Zoha Mohammad⁵⁴, Akash Deep⁵⁵, Tanil Kendirli⁵⁶, Karen Lidsky⁵⁷, Samantha Dallefeld⁵⁸, Helen Flockton⁵⁹, Shruti Agrawal⁶⁰, Krishna Sumanth Siruguppa^{61

62

63}, Michaela Waak⁶⁴, Alfonso Gutiérrez-Mata⁶⁵, Warwick Butt^{66

67}, Sixto Bogantes-Ledezma⁶⁵, Fabricio Sevilla-Acosta⁶⁸, Andres Umaña-Calderón⁶⁵, Adriana Ulate-Campos⁶⁵, Adriana Yock-Corrales⁶⁹, Victor Brodzik Talisa⁴⁴, Hari Krishnan Kanthimathinathan⁷⁰, Michelle E Schober⁷¹, Ericka L Fink⁴⁴; Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID) Investigators

Affiliations

¹ Division of Pediatric Critical Care Medicine, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada.
² Division of Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
³ Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia.
⁴ Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia.
⁵ Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁶ Division of Pediatric Neurology, University of Washington, Seattle Children's Hospital, Seattle.
⁷ Department of Pediatrics, Universidad Nacional de Colombia, Bogotá, Colombia.
⁸ Department of Pediatric Neurology, Faculty of Medicine, Fundación Universitaria de Ciencias de la Salud, Bogotá, Colombia.
⁹ Division of Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus.
¹⁰ Department of Pediatrics, The University of Chicago, Chicago, Illinois.
¹¹ Division of Critical Care, Department of Pediatrics, University Medical Center Children's Hospital, Las Vegas, Nevada.
¹² Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas.
¹³ Division of Pediatric Critical Care Medicine, Department of Pediatrics, Medical University of South Carolina, Charleston.
¹⁴ Division of Critical Care, Department of Pediatrics, University of Maryland Medical Center, Baltimore.
¹⁵ 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.
¹⁶ Division of Pediatric Critical Care, Department of Pediatrics, Carver College of Medicine, University of Iowa Health Care, Iowa City.
¹⁷ Division of Pediatric Critical Care Medicine, Penn State College of Medicine, The Pennsylvania State University, Hershey.
¹⁸ Department of Pediatrics, University of São Paulo, São Paulo, Brazil.
¹⁹ Department of Pediatrics, University of North Carolina at Chapel Hill Hospitals, Chapel Hill.
²⁰ Pediatric Intensive Care Unit, Hospital Metropolitano, Quito, Ecuador.
²¹ Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle.
²² Division of Pediatric Critical Care and Hospital Medicine, Department of Pediatrics, Columbia University Irving Medical Center, New York, New York.
²³ 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 Division of Child Neurology, Department of Neurology, Columbia University Irving Medical Center, New York, New York.
²⁵ Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
²⁶ Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia.
²⁷ Division of Pediatric Critical Care, Department of Pediatrics, Hospital de Emergencia Villa El Salvador, Lima, Peru.
²⁸ Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
²⁹ Pediatric Critical Care and Neurotrauma Recovery Program, Department of Pediatrics, Oregon Health & Science University, Portland.
³⁰ Division of Pediatric Critical Care, Department of Pediatrics, Oregon Health & Science University, Portland.
³¹ Department of Neurology, New York University Langone Health, New York.
³² Division of Pediatric Critical Care, Department of Pediatrics, Hassenfeld Children's Hospital, New York University Langone Health, New York.
³³ Division of Pediatric Critical Care Medicine, Department of Pediatrics and Adolescent Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota.
³⁴ Division of Neurology, Barrow Neurological Institute at Phoenix Children's Hospital, The University of Arizona, College of Medicine, Phoenix.
³⁵ Department of Neurology, Washington University School of Medicine in St Louis, St Louis, Missouri.
³⁶ Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine in St Louis, St Louis, Missouri.
³⁷ Mallinckrodt Institute of Radiology, Washington University School of Medicine in St Louis, St Louis, Missouri.
³⁸ Division of Pediatric Critical Care Medicine, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia.
³⁹ Division of Pediatric Critical Care Medicine, Department of Pediatrics, Standford University Medicine, Lucile Packard Children's Hospital Stanford, Stanford, California.
⁴⁰ Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
⁴¹ Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison.
⁴² Division of Child Neurology, Department of Neurology, Medical College of Wisconsin, Children's Wisconsin, Milwaukee.
⁴³ Department of Pediatrics, Medical College of Wisconsin, Children's Wisconsin, Milwaukee.
⁴⁴ Division of Pediatric Critical Care Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
⁴⁵ Department of Pediatrics, Hospital Universitario Austral, Buenos Aires, Argentina.
⁴⁶ Division of Pediatric Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston.
⁴⁷ Division of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston.
⁴⁸ Department of Pediatrics, Hospital General de Niños Pedro Elizade, Buenos Aires, Argentina.
⁴⁹ Birmingham Children's Hospital, Birmingham, United Kingdom.
⁵⁰ Aston Institute of Health and Neurodevelopment, Birmingham, United Kingdom.
⁵¹ Aston University, Birmingham, United Kingdom.
⁵² Department of Neurology, Royal London Children's Hospital, London, United Kingdom.
⁵³ Pediatric Critical Care Unit, University Hospital of Wales, Cardiff, United Kingdom.
⁵⁴ Pediatric Intensive Care Unit, University Hospitals Leicester NHS Trust, Leicester, United Kingdom.
⁵⁵ Department of Women and Children's Health, King's College Hospital, London, United Kingdom.
⁵⁶ Department of Pediatric Critical Care Medicine, Ankara University School of Medicine, Ankara, Turkey.
⁵⁷ Division of Pediatric Critical Care Medicine, Wolfson Children's Hospital, Jacksonville, Florida.
⁵⁸ Department of Pediatrics, Dell Children's Hospital, Austin, Texas.
⁵⁹ Paediatric Critical Care Unit, Oxford University Hospitals, Oxford, United Kingdom.
⁶⁰ Paediatric Intensive Care Unit, Cambridge University Hospitals, Cambridge, United Kingdom.
⁶¹ Division of Pediatric Critical Care, Department of Pediatrics, University of California, San Francisco.
⁶² Fresno Medical Education and Research Program, Department of Medicine, University of California, San Francisco, Fresno.
⁶³ Department of Pediatrics, Community Medical Centers, Fresno, California.
⁶⁴ Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia.
⁶⁵ Department of Pediatric Neurology, Dr. Carlos Sáenz Herrera National Children's Hospital, San José, Costa Rica.
⁶⁶ Department of Critical Care, Melbourne Medical School, The University of Melbourne, The Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia.
⁶⁷ Clinical Sciences, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
⁶⁸ Department of Pediatrics, La Anexión Hospital, Guanacaste, Costa Rica.
⁶⁹ Department of Emergency Service, Dr. Carlos Sáenz Herrera National Children's Hospital, San José, Costa Rica.
⁷⁰ West Midlands Regional Genetics Laboratory, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, United Kingdom.
⁷¹ Division of Critical Care, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City.

PMID: 38857050
PMCID: PMC11165382
DOI: 10.1001/jamanetworkopen.2024.14122

Multicenter Study

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

Conall Francoeur et al. JAMA Netw Open. 2024.

. 2024 Jun 3;7(6):e2414122.

doi: 10.1001/jamanetworkopen.2024.14122.

Authors

Affiliations

¹ Division of Pediatric Critical Care Medicine, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada.
² Division of Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
³ Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia.
⁴ Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia.
⁵ Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁶ Division of Pediatric Neurology, University of Washington, Seattle Children's Hospital, Seattle.
⁷ Department of Pediatrics, Universidad Nacional de Colombia, Bogotá, Colombia.
⁸ Department of Pediatric Neurology, Faculty of Medicine, Fundación Universitaria de Ciencias de la Salud, Bogotá, Colombia.
⁹ Division of Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus.
¹⁰ Department of Pediatrics, The University of Chicago, Chicago, Illinois.
¹¹ Division of Critical Care, Department of Pediatrics, University Medical Center Children's Hospital, Las Vegas, Nevada.
¹² Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas.
¹³ Division of Pediatric Critical Care Medicine, Department of Pediatrics, Medical University of South Carolina, Charleston.
¹⁴ Division of Critical Care, Department of Pediatrics, University of Maryland Medical Center, Baltimore.
¹⁵ 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.
¹⁶ Division of Pediatric Critical Care, Department of Pediatrics, Carver College of Medicine, University of Iowa Health Care, Iowa City.
¹⁷ Division of Pediatric Critical Care Medicine, Penn State College of Medicine, The Pennsylvania State University, Hershey.
¹⁸ Department of Pediatrics, University of São Paulo, São Paulo, Brazil.
¹⁹ Department of Pediatrics, University of North Carolina at Chapel Hill Hospitals, Chapel Hill.
²⁰ Pediatric Intensive Care Unit, Hospital Metropolitano, Quito, Ecuador.
²¹ Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle.
²² Division of Pediatric Critical Care and Hospital Medicine, Department of Pediatrics, Columbia University Irving Medical Center, New York, New York.
²³ 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 Division of Child Neurology, Department of Neurology, Columbia University Irving Medical Center, New York, New York.
²⁵ Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
²⁶ Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia.
²⁷ Division of Pediatric Critical Care, Department of Pediatrics, Hospital de Emergencia Villa El Salvador, Lima, Peru.
²⁸ Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
²⁹ Pediatric Critical Care and Neurotrauma Recovery Program, Department of Pediatrics, Oregon Health & Science University, Portland.
³⁰ Division of Pediatric Critical Care, Department of Pediatrics, Oregon Health & Science University, Portland.
³¹ Department of Neurology, New York University Langone Health, New York.
³² Division of Pediatric Critical Care, Department of Pediatrics, Hassenfeld Children's Hospital, New York University Langone Health, New York.
³³ Division of Pediatric Critical Care Medicine, Department of Pediatrics and Adolescent Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota.
³⁴ Division of Neurology, Barrow Neurological Institute at Phoenix Children's Hospital, The University of Arizona, College of Medicine, Phoenix.
³⁵ Department of Neurology, Washington University School of Medicine in St Louis, St Louis, Missouri.
³⁶ Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine in St Louis, St Louis, Missouri.
³⁷ Mallinckrodt Institute of Radiology, Washington University School of Medicine in St Louis, St Louis, Missouri.
³⁸ Division of Pediatric Critical Care Medicine, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia.
³⁹ Division of Pediatric Critical Care Medicine, Department of Pediatrics, Standford University Medicine, Lucile Packard Children's Hospital Stanford, Stanford, California.
⁴⁰ Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
⁴¹ Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison.
⁴² Division of Child Neurology, Department of Neurology, Medical College of Wisconsin, Children's Wisconsin, Milwaukee.
⁴³ Department of Pediatrics, Medical College of Wisconsin, Children's Wisconsin, Milwaukee.
⁴⁴ Division of Pediatric Critical Care Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
⁴⁵ Department of Pediatrics, Hospital Universitario Austral, Buenos Aires, Argentina.
⁴⁶ Division of Pediatric Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston.
⁴⁷ Division of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston.
⁴⁸ Department of Pediatrics, Hospital General de Niños Pedro Elizade, Buenos Aires, Argentina.
⁴⁹ Birmingham Children's Hospital, Birmingham, United Kingdom.
⁵⁰ Aston Institute of Health and Neurodevelopment, Birmingham, United Kingdom.
⁵¹ Aston University, Birmingham, United Kingdom.
⁵² Department of Neurology, Royal London Children's Hospital, London, United Kingdom.
⁵³ Pediatric Critical Care Unit, University Hospital of Wales, Cardiff, United Kingdom.
⁵⁴ Pediatric Intensive Care Unit, University Hospitals Leicester NHS Trust, Leicester, United Kingdom.
⁵⁵ Department of Women and Children's Health, King's College Hospital, London, United Kingdom.
⁵⁶ Department of Pediatric Critical Care Medicine, Ankara University School of Medicine, Ankara, Turkey.
⁵⁷ Division of Pediatric Critical Care Medicine, Wolfson Children's Hospital, Jacksonville, Florida.
⁵⁸ Department of Pediatrics, Dell Children's Hospital, Austin, Texas.
⁵⁹ Paediatric Critical Care Unit, Oxford University Hospitals, Oxford, United Kingdom.
⁶⁰ Paediatric Intensive Care Unit, Cambridge University Hospitals, Cambridge, United Kingdom.
⁶¹ Division of Pediatric Critical Care, Department of Pediatrics, University of California, San Francisco.
⁶² Fresno Medical Education and Research Program, Department of Medicine, University of California, San Francisco, Fresno.
⁶³ Department of Pediatrics, Community Medical Centers, Fresno, California.
⁶⁴ Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia.
⁶⁵ Department of Pediatric Neurology, Dr. Carlos Sáenz Herrera National Children's Hospital, San José, Costa Rica.
⁶⁶ Department of Critical Care, Melbourne Medical School, The University of Melbourne, The Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia.
⁶⁷ Clinical Sciences, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
⁶⁸ Department of Pediatrics, La Anexión Hospital, Guanacaste, Costa Rica.
⁶⁹ Department of Emergency Service, Dr. Carlos Sáenz Herrera National Children's Hospital, San José, Costa Rica.
⁷⁰ West Midlands Regional Genetics Laboratory, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, United Kingdom.
⁷¹ Division of Critical Care, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City.

PMID: 38857050
PMCID: PMC11165382
DOI: 10.1001/jamanetworkopen.2024.14122

Erratum in

Byline Errors.
[No authors listed] [No authors listed] JAMA Netw Open. 2024 Jul 1;7(7):e2428458. doi: 10.1001/jamanetworkopen.2024.28458. JAMA Netw Open. 2024. PMID: 39028673 Free PMC article. No abstract available.

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Wainwright reported receiving personal fees from Sage Therapeutics during the conduct of the study. Dr Wellnitz reported receiving a subgrant from the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH); a subcontract from the Centers for Disease Control and Prevention under Boston Children’s Hospital; and personal fees from the Pediatric Pandemic Network for work as a pediatric disaster preparedness subject matter expert and being a sponsor for the University of Pennsylvania outside the submitted work. Dr Geneslaw reported receiving grants from the National Center for Advancing Translational Sciences, NIH during the conduct of the study. Dr Muller reported receiving grants from Ansun BioPharma, Astellas Pharma, AstraZeneca, Eli Lilly & Company, Enanta Pharmaceuticals, F. Hoffman-La Roche, Gilead Sciences, Janssen Biotech, Karius, Inc, Melinta Therapeutics, Merck, Moderna, Nabriva Therapeutics, Paratek Pharmaceuticals, Inc, Pfizer, and Tetraphase Pharmaceuticals, Inc and personal fees from AstraZeneca, Astellas Pharma, DiaSorin Molecular LLC, Invivyd, Sanofi Pasteur LLC, and Enanta Pharmaceuticals outside the submitted work. Dr Williams reported receiving funding from the Neurocritical Care Society through the University of Pittsburgh during the conduct of the study and receiving grants from the NIH outside the submitted work. Dr Dapul reported receiving honorarium from Delex Pharma International, Inc for a virtual lecture outside the submitted work. Dr Appavu reported receiving grants from the Pediatric Epilepsy Research Foundation, the US Department of Defense, and the American Heart Association outside the submitted work. Dr Agner reported receiving grants from the Child Neurologist Career Development Program, National Institute of Neurological Disorders and Stroke, NIH, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, to the Intellectual and Developmental Disabilities Research Center at Washington University School of Medicine in St Louis outside the submitted work. Dr Chang reported receiving grants from the NIH during the conduct of the study. Dr Fink reported receiving grants from the NIH and personal fees from the American Board of Pediatrics outside the submitted work.

Comment in

Severe Neurological Sequelae in Pediatric Patients with SARS-CoV-2 or MIS-C.
Wolf MS. Wolf MS. JAMA Netw Open. 2024 Jun 3;7(6):e2414127. doi: 10.1001/jamanetworkopen.2024.14127. JAMA Netw Open. 2024. PMID: 38857053 No abstract available.

Cited by

Neurologic and Psychological Outcomes 2 Years After Multisystem Inflammatory Syndrome in Children.
Rollins CK, Wypij D, Zambrano LD, Calderon J, Taylor AM, Worhach J, Rodriguez S, Licht PA, Maiman M, Hart N, Son MBF, Kossowsky J, Friedman ML, Hobbs CV, Kong M, Maddux AB, McGuire JL, Staat MA, Yonker LM, Mazumdar M, Newburger JW, Randolph AG, Campbell AP; Overcoming COVID-19 Investigators. Rollins CK, et al. JAMA Netw Open. 2025 Jun 2;8(6):e2512487. doi: 10.1001/jamanetworkopen.2025.12487. JAMA Netw Open. 2025. PMID: 40455448 Free PMC article.
Six clinical phenotypes with prognostic implications were identified by unsupervised machine learning in children and adolescents with SARS-CoV-2 infection: results from a German nationwide registry.
Shi Y, Strobl R, Berner R, Armann J, Scheithauer S, Grill E. Shi Y, et al. Respir Res. 2024 Oct 30;25(1):392. doi: 10.1186/s12931-024-03018-3. Respir Res. 2024. PMID: 39478555 Free PMC article.
Byline Errors.
[No authors listed] [No authors listed] JAMA Netw Open. 2024 Jul 1;7(7):e2428458. doi: 10.1001/jamanetworkopen.2024.28458. JAMA Netw Open. 2024. PMID: 39028673 Free PMC article. No abstract available.
An Update on Multi-System Inflammatory Syndrome in Children.
Goel AR, Yalcindag A. Goel AR, et al. Curr Rheumatol Rep. 2025 Jan 30;27(1):16. doi: 10.1007/s11926-025-01182-z. Curr Rheumatol Rep. 2025. PMID: 39883190 Review.

References

1. Castagnoli R, Votto M, Licari A, et al. . Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review. JAMA Pediatr. 2020;174(9):882-889. doi:10.1001/jamapediatrics.2020.1467 - DOI - PubMed
1. Lu X, Zhang L, Du H, et al. ; Chinese Pediatric Novel Coronavirus Study Team . SARS-CoV-2 infection in children. N Engl J Med. 2020;382(17):1663-1665. doi:10.1056/NEJMc2005073 - DOI - PMC - PubMed
1. Guan WJ, Ni ZY, Hu Y, et al. ; China Medical Treatment Expert Group for Covid-19 . Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720. doi:10.1056/NEJMoa2002032 - DOI - PMC - PubMed
1. COVID-19 Mental Disorders Collaborators . Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. Lancet. 2021;398(10312):1700-1712. doi:10.1016/S0140-6736(21)02143-7 - DOI - PMC - PubMed
1. Huang L, Yao Q, Gu X, et al. . 1-Year outcomes in hospital survivors with COVID-19: a longitudinal cohort study. Lancet. 2021;398(10302):747-758. doi:10.1016/S0140-6736(21)01755-4 - DOI - PMC - PubMed

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[1] Castagnoli R, Votto M, Licari A, et al. . Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review. JAMA Pediatr. 2020;174(9):882-889. doi:10.1001/jamapediatrics.2020.1467 - DOI - PubMed

[2] Castagnoli R, Votto M, Licari A, et al. . Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review. JAMA Pediatr. 2020;174(9):882-889. doi:10.1001/jamapediatrics.2020.1467 - DOI - PubMed

[3] Lu X, Zhang L, Du H, et al. ; Chinese Pediatric Novel Coronavirus Study Team . SARS-CoV-2 infection in children. N Engl J Med. 2020;382(17):1663-1665. doi:10.1056/NEJMc2005073 - DOI - PMC - PubMed

[4] Lu X, Zhang L, Du H, et al. ; Chinese Pediatric Novel Coronavirus Study Team . SARS-CoV-2 infection in children. N Engl J Med. 2020;382(17):1663-1665. doi:10.1056/NEJMc2005073 - DOI - PMC - PubMed

[5] Guan WJ, Ni ZY, Hu Y, et al. ; China Medical Treatment Expert Group for Covid-19 . Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720. doi:10.1056/NEJMoa2002032 - DOI - PMC - PubMed

[6] Guan WJ, Ni ZY, Hu Y, et al. ; China Medical Treatment Expert Group for Covid-19 . Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720. doi:10.1056/NEJMoa2002032 - DOI - PMC - PubMed

[7] COVID-19 Mental Disorders Collaborators . Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. Lancet. 2021;398(10312):1700-1712. doi:10.1016/S0140-6736(21)02143-7 - DOI - PMC - PubMed

[8] COVID-19 Mental Disorders Collaborators . Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. Lancet. 2021;398(10312):1700-1712. doi:10.1016/S0140-6736(21)02143-7 - DOI - PMC - PubMed

[9] Huang L, Yao Q, Gu X, et al. . 1-Year outcomes in hospital survivors with COVID-19: a longitudinal cohort study. Lancet. 2021;398(10302):747-758. doi:10.1016/S0140-6736(21)01755-4 - DOI - PMC - PubMed

[10] Huang L, Yao Q, Gu X, et al. . 1-Year outcomes in hospital survivors with COVID-19: a longitudinal cohort study. Lancet. 2021;398(10302):747-758. doi:10.1016/S0140-6736(21)01755-4 - DOI - PMC - PubMed

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

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

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