Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome
Creators: name: Hume, Janet R.
name: Newhams, Margaret M.
name: Loftis, Laura L.
name: Tarquinio, Keiko M.
name: Schuster, Jennifer E.
name: Munoz, Alvaro Coronado
name: Babbitt, Christopher J.
name: Giuliano, John S.
name: Poussaint, Tina Y.
name: Randolph, Adrienne G.
name: Patel, Manish M.
name: Shein, Steven L.
name: Gertz, Shira J.
name: Maamari, Mia
name: Levy, Emily R.
name: Rowan, Courtney M.
name: Keenaghan, Michael A.
name: Hobbs, Charlotte V.
name: Spinella, Philip C.
name: Hall, Mark W.
name: Staat, Mary A.
name: Thomas, Neal J.
name: Feldstein, Leora R.
name: Cvijanovich, Natalie Z.
name: Mack, Elizabeth H.
name: Maddux, Aline B.
name: Overcoming COVID-19 Investigators
name: McLaughlin, Gwenn E.
name: Nofziger, Ryan A.
name: Kong, Michele
name: Michelson, Kelly N.
name: Irby, Katherine
name: Kleinman, Lawrence C.
name: Wellnitz, Kari
name: Clouser, Katharine N.
name: Singh, Aalok R.
name: McGuire, John K.
name: Walker, Tracie C.
name: LaRovere, Kerri L.
name: Dapul, Heda
name: Flori, Heidi R.
name: Doymaz, Sule
name: Young, Cameron C.
name: Son, Mary Beth F.
name: Carroll, Christopher L.
name: Fitzgerald, Julie C.
name: Riggs, Becky J.
name: Halasa, Natasha B.
name: Tenforde, Mark W.
Publisher: name: American Medical Association (AMA)
Year: 2021

description: <p>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 &lt;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&thinsp;=&thinsp;15; 5 with splenial lesions), stroke (n&thinsp;=&thinsp;12), central nervous system infection/demyelination (n&thinsp;=&thinsp;8), Guillain-Barr&eacute; syndrome/variants (n&thinsp;=&thinsp;4), and acute fulminant cerebral edema (n&thinsp;=&thinsp;4). Compared with those without life-threatening conditions (n&thinsp;=&thinsp;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 &mu;g/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.</p>