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, 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, First Name and Middle Initial(s)* Last Name*, 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

Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. 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. Severe acute respiratory syndrome coronavirus 2. Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. 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. 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.