Kerri L LaRovere1, Becky J Riggs2, Tina Y Poussaint3, Cameron C Young4, Margaret M Newhams4, Mia Maamari5, Tracie C Walker6, Aalok R Singh7, Heda Dapul8, Charlotte V Hobbs9, Gwenn E McLaughlin10, Mary Beth F Son11, Aline B Maddux12, Katharine N Clouser13, Courtney M Rowan14, John K McGuire15, Julie C Fitzgerald16, Shira J Gertz17, Steven L Shein18, Alvaro Coronado Munoz19, Neal J Thomas20, Katherine Irby21, Emily R Levy22, Mary A Staat23, Mark W Tenforde24,25, Leora R Feldstein24,25, Natasha B Halasa26, John S Giuliano27, Mark W Hall28, Michele Kong29, Christopher L Carroll30, Jennifer E Schuster31, Sule Doymaz32, Laura L Loftis33, Keiko M Tarquinio34, Christopher J Babbitt35, Ryan A Nofziger36, Lawrence C Kleinman37, Michael A Keenaghan38, Natalie Z Cvijanovich39, Philip C Spinella40, Janet R Hume41, Kari Wellnitz42, Elizabeth H Mack43, Kelly N Michelson44, Heidi R Flori45, Manish M Patel24,25, Adrienne G Randolph4,46. 1. Department of Neurology, Boston Children's Hospital, Boston, Massachusetts. 2. Division of Pediatric Anesthesiology and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland. 3. Department of Radiology, Boston Children's Hospital, Boston, Massachusetts. 4. Division of Critical Care Medicine, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts. 5. Division of Critical Care Medicine, Department of Pediatrics, University of Texas Southwestern, Children's Health Medical Center Dallas. 6. Department of Pediatrics, University of North Carolina at Chapel Hill Children's Hospital, Chapel Hill. 7. Pediatric Critical Care Division, Maria Fareri Children's Hospital at Westchester Medical Center and New York Medical College, Valhalla. 8. Division of Pediatric Critical Care Medicine, Department of Pediatrics, New York University Grossman School of Medicine, New York. 9. Division of Infectious Diseases, Department of Pediatrics, Department of Microbiology, University of Mississippi Medical Center, Jackson. 10. Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida. 11. Division of Immunology, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts. 12. Section of Critical Care Medicine, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora. 13. Department of Pediatrics, Joseph M. Sanzari Children's Hospital at Hackensack University Medical Center, Hackensack, New Jersey. 14. Division of Pediatric Critical Care Medicine, Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis. 15. Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Washington, Seattle. 16. Division of Critical Care, Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia. 17. Division of Pediatric Critical Care, Department of Pediatrics, Saint Barnabas Medical Center, Livingston, New Jersey. 18. Division of Pediatric Critical Care Medicine, Rainbow Babies and Children's Hospital, Cleveland, Ohio. 19. Pediatric Critical Care Division, Department of Pediatrics, University of Texas Health Science Center at Houston, Houston. 20. Department of Pediatrics, Penn State Hershey Children's Hospital, Pennsylvania State University College of Medicine, Hershey. 21. Section of Pediatric Critical Care, Department of Pediatrics, Arkansas Children's Hospital, Little Rock. 22. Divisions of Pediatric Infectious Diseases and Pediatric Critical Care Medicine, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota. 23. Department of Pediatrics, University of Cincinnati, Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 24. COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia. 25. Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia. 26. Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee. 27. Division of Critical Care, Yale University School of Medicine, New Haven, Connecticut. 28. Division of Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio. 29. Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham. 30. Division of Critical Care, Connecticut Children's, Hartford, Connecticut. 31. Division of Pediatric Infectious Diseases, Department of Pediatrics, Children's Mercy Kansas City, Kansas City, Missouri. 32. Division of Pediatric Critical Care, Department of Pediatrics, State University of New York Downstate Health Sciences University, Brooklyn. 33. Section of Critical Care Medicine, Department of Pediatrics, Texas Children's Hospital, Houston. 34. Division of Critical Care Medicine, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia. 35. Miller Children's and Women's Hospital of Long Beach, Long Beach, California. 36. Division of Critical Care Medicine, Akron Children's Hospital, Akron, Ohio. 37. Division of Population Health, Quality, and Implementation Sciences (PopQuIS), Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey. 38. Pediatric Critical Care, New York City Health and Hospitals, Kings County Hospital, Brooklyn, New York. 39. Division of Critical Care Medicine, University of California, San Francisco, Benioff Children's Hospital, Oakland. 40. Division of Critical Care, Department of Pediatrics, Washington University School of Medicine in St Louis, St Louis, Missouri. 41. Division of Pediatric Critical Care, University of Minnesota Masonic Children's Hospital, Minneapolis. 42. Division of Pediatric Critical Care, Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa. 43. Division of Pediatric Critical Care Medicine, Medical University of South Carolina, Charleston. 44. Division of Critical Care Medicine, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois. 45. Division of Pediatric Critical Care Medicine, Department of Pediatrics, Mott Children's Hospital and University of Michigan, Ann Arbor. 46. Departments of Anaesthesia and Pediatrics, Harvard Medical School, Boston, Massachusetts.
Abstract
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.
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.
Authors: Dongngan T Truong; Felicia L Trachtenberg; Gail D Pearson; Audrey Dionne; Matthew D Elias; Kevin Friedman; Kerri H Hayes; Lynn Mahony; Brian W McCrindle; Matthew E Oster; Victoria Pemberton; Andrew J Powell; Mark W Russell; Lara S Shekerdemian; Mary Beth Son; Michael Taylor; Jane W Newburger Journal: Am Heart J Date: 2021-08-19 Impact factor: 4.749
Authors: Michelle Elena Schober; Courtney Leigh Robertson; Mark Stephen Wainwright; Juan David Roa; Ericka Linn Fink Journal: Neurocrit Care Date: 2021-06-28 Impact factor: 3.210
Authors: Stephen T J Ray; Omar Abdel-Mannan; Mario Sa; Charlotte Fuller; Greta K Wood; Karen Pysden; Michael Yoong; Helen McCullagh; David Scott; Martin McMahon; Naomi Thomas; Micheal Taylor; Marjorie Illingworth; Nadine McCrea; Victoria Davies; William Whitehouse; Sameer Zuberi; Keira Guthrie; Evangeline Wassmer; Nikit Shah; Mark R Baker; Sangeeta Tiwary; Hui Jeen Tan; Uma Varma; Dipak Ram; Shivaram Avula; Noelle Enright; Jane Hassell; Amy L Ross Russell; Ram Kumar; Rachel E Mulholland; Sarah Pett; Ian Galea; Rhys H Thomas; Ming Lim; Yael Hacohen; Tom Solomon; Michael J Griffiths; Benedict D Michael; Rachel Kneen Journal: Lancet Child Adolesc Health Date: 2021-07-15