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. 2023 Jan 1;80(1):91-98.
doi: 10.1001/jamaneurol.2022.3881.

Changes in Distribution of Severe Neurologic Involvement in US Pediatric Inpatients With COVID-19 or Multisystem Inflammatory Syndrome in Children in 2021 vs 2020

Kerri L LaRovere  1 , Tina Y Poussaint  2 , Cameron C Young  3 , Margaret M Newhams  3 , Suden Kucukak  3 , Katherine Irby  4 , Michele Kong  5 , Stephanie P Schwartz  6 , Tracie C Walker  6 , Melania M Bembea  7 , Kari Wellnitz  8 , Kevin M Havlin  9 , Natalie Z Cvijanovich  10 , Mark W Hall  11 , Julie C Fitzgerald  12 , Jennifer E Schuster  13 , Charlotte V Hobbs  14 , Natasha B Halasa  15 , Aalok R Singh  16 , Elizabeth H Mack  17 , Tamara T Bradford  18 , Shira J Gertz  19 , Adam J Schwarz  20 , Katri V Typpo  21 , Laura L Loftis  22 , John S Giuliano Jr  23 , Steven M Horwitz  24 , Katherine V Biagas  25 , Katharine N Clouser  26 , Courtney M Rowan  27 , Aline B Maddux  28 , Vijaya L Soma  29 , Christopher J Babbitt  30 , Cassyanne L Aguiar  31 , Amanda R Kolmar  32 , Sabrina M Heidemann  33 , Helen Harvey  34 , Laura D Zambrano  35 , Angela P Campbell  35 , Adrienne G Randolph  3   36 ; Overcoming COVID-19 Investigators
Collaborators, Affiliations

Changes in Distribution of Severe Neurologic Involvement in US Pediatric Inpatients With COVID-19 or Multisystem Inflammatory Syndrome in Children in 2021 vs 2020

Kerri L LaRovere et al. JAMA Neurol. .

Abstract

Importance: In 2020 during the COVID-19 pandemic, neurologic involvement was common in children and adolescents hospitalized in the United States for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complications.

Objective: To provide an update on the spectrum of SARS-CoV-2-related neurologic involvement among children and adolescents in 2021.

Design, setting, and participants: Case series investigation of patients reported to public health surveillance hospitalized with SARS-CoV-2-related illness between December 15, 2020, and December 31, 2021, in 55 US hospitals in 31 states with follow-up at hospital discharge. A total of 2253 patients were enrolled during the investigation period. Patients suspected of having multisystem inflammatory syndrome in children (MIS-C) who did not meet criteria (n = 85) were excluded. Patients (<21 years) with positive SARS-CoV-2 test results (reverse transcriptase-polymerase chain reaction and/or antibody) meeting criteria for MIS-C or acute COVID-19 were included in the analysis.

Exposure: SARS-CoV-2 infection.

Main outcomes and measures: Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening neurologic involvement was adjudicated by experts based on clinical and/or neuroradiological features. Type and severity of neurologic involvement, laboratory and imaging data, vaccination status, and hospital discharge outcomes (death or survival with new neurologic deficits).

Results: Of 2168 patients included (58% male; median age, 10.3 years), 1435 (66%) met criteria for MIS-C, and 476 (22%) had documented neurologic involvement. Patients with neurologic involvement vs without were older (median age, 12 vs 10 years) and more frequently had underlying neurologic disorders (107 of 476 [22%] vs 240 of 1692 [14%]). Among those with neurologic involvement, 42 (9%) developed acute SARS-CoV-2-related life-threatening conditions, including central nervous system infection/demyelination (n = 23; 15 with possible/confirmed encephalitis, 6 meningitis, 1 transverse myelitis, 1 nonhemorrhagic leukoencephalopathy), stroke (n = 11), severe encephalopathy (n = 5), acute fulminant cerebral edema (n = 2), and Guillain-Barré syndrome (n = 1). Ten of 42 (24%) survived with new neurologic deficits at discharge and 8 (19%) died. Among patients with life-threatening neurologic conditions, 15 of 16 vaccine-eligible patients (94%) were unvaccinated.

Conclusions and relevance: SARS-CoV-2-related neurologic involvement persisted in US children and adolescents hospitalized for COVID-19 or MIS-C in 2021 and was again mostly transient. Central nervous system infection/demyelination accounted for a higher proportion of life-threatening conditions, and most vaccine-eligible patients were unvaccinated. COVID-19 vaccination may prevent some SARS-CoV-2-related neurologic complications and merits further study.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Poussaint reported grants from the National Institutes of Health (NIH) for the PBTC Neuroimaging Center and personal fees from Springer Publishing outside the submitted work. Dr Bembea reported grants from the NIH, National Institute of Neurological Disorders and Stroke, and Grifols outside the submitted work. Dr Hall reported personal fees for serving on data and safety monitoring boards from AbbVie and La Jolla Pharmaceutical, personal fees from the American Board of Pediatrics Service for subboard service outside the submitted work, and patents for WO 2020/168250 and WO 2020/168254, both licensed to Kiadis. Dr Schuster reported grants from Merck outside the submitted work. Dr Hobbs reported consulting fees from Biomerieux and dynamed.com outside the submitted work. Dr Halasa reported grants from Sanofi and Quidel outside the submitted work. Dr Rowan reported grants from the National Heart, Lung, and Blood Institute outside the submitted work. Dr Randolph reported royalties from UpToDate and grants from the NIH outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Representative Central Nervous System Images From Patients With Life-threatening COVID-19–Related Neurologic Involvement
A, Teenager presented with acute respiratory failure, fever, acute onset of altered awareness, confusion, agitation, and difficulty walking. Axial T2 images show myositis of the facial muscles with stranding of subcutaneous fat, sinusitis, and cavernous sinus thrombosis with T2 hypointense signal and reduced diffusivity (apparent diffusion coefficient [ADC] map). Coronal and axial T1 images with contrast demonstrate dural enhancement, filling defects in superior ophthalmic veins and cavernous sinuses consistent with thrombosis (arrowheads). The patient’s brain injury evolved to diagnosis of death by neurologic criteria. B, Teenager with history of obesity, hypertension, and diabetes presented with 3 weeks of fever, confusion, headache, seizures, orofacial dyskinesias, agitation, slurred speech, difficulty walking, chorea, and left-sided weakness. Axial T2 fluid-attenuated inversion recovery (FLAIR) images demonstrate T2 hyperintense signal in bilateral cerebellar, bilateral temporal, and bilateral centrum semiovale white matter with reduced diffusivity. There was no enhancement, and susceptibility was present in lesions consistent with punctate blood products (not shown). The patient later died by brain death. C, Teenager presented with 3 weeks of fever, headaches, lethargy, confusion, seizure, vomiting, blurry vision, and nystagmus. Axial T2 FLAIR images demonstrate moderate enlargement of lateral and third ventricles, T2 prolongation in bilateral cerebellar hemispheres, bilateral thalami, and bifrontal white matter and cortex with reduced diffusivity on trace diffusion images and no enhancement (not shown). ADEM indicates acute disseminated encephalomyelitis.
See this image and copyright information in PMC

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