Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome
Kerri L LaRovere, Becky J Riggs, Tina Y Poussaint, Cameron C Young, Margaret M Newhams, Mia Maamari, Tracie C Walker, Aalok R Singh, Heda Dapul, Charlotte V Hobbs, Gwenn E McLaughlin, Mary Beth F Son, Aline B Maddux, Katharine N Clouser, Courtney M Rowan, John K McGuire, Julie C Fitzgerald, Shira J Gertz, Steven L Shein, Alvaro Coronado Munoz, Neal J Thomas, Katherine Irby, Emily R Levy, Mary A Staat, Mark W Tenforde, Leora R Feldstein, Natasha B Halasa, John S Giuliano Jr, Mark W Hall, Michele Kong, Christopher L Carroll, Jennifer E Schuster, Sule Doymaz, Laura L Loftis, Keiko M Tarquinio, Christopher J Babbitt, Ryan A Nofziger, Lawrence C Kleinman, Michael A Keenaghan, Natalie Z Cvijanovich, Philip C Spinella, Janet R Hume, Kari Wellnitz, Elizabeth H Mack, Kelly N Michelson, Heidi R Flori, Manish M Patel, Adrienne G Randolph, Overcoming COVID-19 Investigators, First Name And Middle Initial S Last Name Suffix*, Mary G Gaspers, Katri V Typpo, Ronald C Sanders, Adam J Schwarz, Helen Harvey, Matt S Zinter, Peter M Mourani, Bria M Coates, Guru Bhoojhawon, Kevin M Havlin, Vicki L Montgomery, Janice E Sullivan, Tamara T Bradford, Melania M Bembea, Susan V Lipton, Ana Lia Graciano, Sabrina R Chen, Suden Kucukak, Jane W Newburger, Ryan W Carroll, Neil D Fernandes, Phoebe H Yager, Kimberly L Marohn, Sabrina M Heidemann, Melissa L Cullimore, Russell J McCulloh, Steven M Horwitz, Simon Li, Rowan F Walsh, Adam J Ratner, Vijaya L Soma, Jennifer K Gillen, Sheemon P Zackai, Kate G Ackerman, Jill M Cholette, Ilana Harwayne-Gidansky, Saul R Hymes, Philip J Overby, Stephanie P Schwartz, Amanda N Lansell, Monica L Koncicki, Joseph Carcillo, Ericka Fink, Dai Kimura, Cindy Bowens, Hillary Crandall, Lincoln S Smith, Pelin Cengiz, Kerri L LaRovere, Becky J Riggs, Tina Y Poussaint, Cameron C Young, Margaret M Newhams, Mia Maamari, Tracie C Walker, Aalok R Singh, Heda Dapul, Charlotte V Hobbs, Gwenn E McLaughlin, Mary Beth F Son, Aline B Maddux, Katharine N Clouser, Courtney M Rowan, John K McGuire, Julie C Fitzgerald, Shira J Gertz, Steven L Shein, Alvaro Coronado Munoz, Neal J Thomas, Katherine Irby, Emily R Levy, Mary A Staat, Mark W Tenforde, Leora R Feldstein, Natasha B Halasa, John S Giuliano Jr, Mark W Hall, Michele Kong, Christopher L Carroll, Jennifer E Schuster, Sule Doymaz, Laura L Loftis, Keiko M Tarquinio, Christopher J Babbitt, Ryan A Nofziger, Lawrence C Kleinman, Michael A Keenaghan, Natalie Z Cvijanovich, Philip C Spinella, Janet R Hume, Kari Wellnitz, Elizabeth H Mack, Kelly N Michelson, Heidi R Flori, Manish M Patel, Adrienne G Randolph, Overcoming COVID-19 Investigators, First Name And Middle Initial S Last Name Suffix*, Mary G Gaspers, Katri V Typpo, Ronald C Sanders, Adam J Schwarz, Helen Harvey, Matt S Zinter, Peter M Mourani, Bria M Coates, Guru Bhoojhawon, Kevin M Havlin, Vicki L Montgomery, Janice E Sullivan, Tamara T Bradford, Melania M Bembea, Susan V Lipton, Ana Lia Graciano, Sabrina R Chen, Suden Kucukak, Jane W Newburger, Ryan W Carroll, Neil D Fernandes, Phoebe H Yager, Kimberly L Marohn, Sabrina M Heidemann, Melissa L Cullimore, Russell J McCulloh, Steven M Horwitz, Simon Li, Rowan F Walsh, Adam J Ratner, Vijaya L Soma, Jennifer K Gillen, Sheemon P Zackai, Kate G Ackerman, Jill M Cholette, Ilana Harwayne-Gidansky, Saul R Hymes, Philip J Overby, Stephanie P Schwartz, Amanda N Lansell, Monica L Koncicki, Joseph Carcillo, Ericka Fink, Dai Kimura, Cindy Bowens, Hillary Crandall, Lincoln S Smith, Pelin Cengiz
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.
Conflict of interest statement
Conflict of Interest Disclosures: Dr Riggs reported grants from the US Centers for Disease Control and Prevention (CDC) funding through Boston Children's Hospital during the conduct of the study. Dr Newhams reported grants from the CDC during the conduct of the study. Dr Maamari reported other support from the CDC during the conduct of the study. Dr McLaughlin reported grants from Boston Children's Hospital and the CDC during the conduct of the study. Dr Maddux reported grants from the National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development during the conduct of the study. Dr Rowan reported grants from the CDC during the conduct of the study and from the NIH outside the submitted work. Dr McGuire reported grants from the CDC during the conduct of the study. Dr Fitzgerald reported grants from the CDC during the conduct of the study and from the NIH outside the submitted work. Dr Gertz reported grants from Boston Children’s Hospital as a passthrough for the CDC during the conduct of the study. Dr Shein reported grants from the CDC during the conduct of the study. Dr Coronado Munoz reported grants from the CDC during the conduct of the study. Dr Levy reported grants from the CDC during the conduct of the study and from the National Institute of Allergy and Infectious Diseases outside the submitted work. Dr Staat reported other support from Boston Children's Hospital during the conduct of the study. Dr Halasa reported grants from the CDC during the conduct of the study; grants from Sanofi and Quidel; and personal fees from Genentech outside the submitted work. Dr Hall reported grants from the CDC during the conduct of the study and personal fees from LaJolla Pharmaceuticals outside the submitted work. Dr Schuster reported other from the CDC during the conduct of the study; other support from Merck; and grants from the CDC outside the submitted work. Dr Doymaz reported grants from the CDC during the conduct of the study. Dr Tarquinio reported grants from the CDC during the conduct of the study. Dr Nofziger reported other from the CDC during the conduct of the study. Dr Kleinman reported grants from Boston Children's Hospital during the conduct of the study and grants from Health Services Research Administration and NICHD outside the submitted work. Dr Cvijanovich reported grants from the CDC during the conduct of the study and grants from Cincinnati Children’s Medical Center and Boston Children's Hospital outside the submitted work. Dr Hume reported grants from the CDC during the conduct of the study. Dr Wellnitz reported other support from the CDC and NIH during the conduct of the study. Dr Michelson reported grants from the CDC during the conduct of the study and grants National Palliative Care Research Center and the National Institutes of Health outside the submitted work. Dr Randolph reported grants from the CDC during the conduct of the study and other support from UpToDate outside the submitted work. Dr Poussaint reported receiving grants from the National Institutes of Health and royalties from Springer Publishing outside of the submitted work. No other disclosures were reported.
Figures
Source: PubMed