Neurological manifestations of SARS-CoV-2 infection in hospitalised children and adolescents in the UK: a prospective national cohort study

Abstract

Background: The spectrum of neurological and psychiatric complications associated with paediatric SARS-CoV-2 infection is poorly understood. We aimed to analyse the range and prevalence of these complications in hospitalised children and adolescents.

Methods: We did a prospective national cohort study in the UK using an online network of secure rapid-response notification portals established by the CoroNerve study group. Paediatric neurologists were invited to notify any children and adolescents (age <18 years) admitted to hospital with neurological or psychiatric disorders in whom they considered SARS-CoV-2 infection to be relevant to the presentation. Patients were excluded if they did not have a neurological consultation or neurological investigations or both, or did not meet the definition for confirmed SARS-CoV-2 infection (a positive PCR of respiratory or spinal fluid samples, serology for anti-SARS-CoV-2 IgG, or both), or the Royal College of Paediatrics and Child Health criteria for paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Individuals were classified as having either a primary neurological disorder associated with COVID-19 (COVID-19 neurology group) or PIMS-TS with neurological features (PIMS-TS neurology group). The denominator of all hospitalised children and adolescents with COVID-19 was collated from National Health Service England data.

Findings: Between April 2, 2020, and Feb 1, 2021, 52 cases were identified; in England, there were 51 cases among 1334 children and adolescents hospitalised with COVID-19, giving an estimated prevalence of 3·8 (95% CI 2·9-5·0) cases per 100 paediatric patients. 22 (42%) patients were female and 30 (58%) were male; the median age was 9 years (range 1-17). 36 (69%) patients were Black or Asian, 16 (31%) were White. 27 (52%) of 52 patients were classified into the COVID-19 neurology group and 25 (48%) were classified into the PIMS-TS neurology group. In the COVID-19 neurology group, diagnoses included status epilepticus (n=7), encephalitis (n=5), Guillain-Barré syndrome (n=5), acute demyelinating syndrome (n=3), chorea (n=2), psychosis (n=2), isolated encephalopathy (n=2), and transient ischaemic attack (n=1). The PIMS-TS neurology group more often had multiple features, which included encephalopathy (n=22 [88%]), peripheral nervous system involvement (n=10 [40%]), behavioural change (n=9 [36%]), and hallucinations at presentation (n=6 [24%]). Recognised neuroimmune disorders were more common in the COVID-19 neurology group than in the PIMS-TS neurology group (13 [48%] of 27 patients vs 1 [<1%] of 25 patients, p=0·0003). Compared with the COVID-19 neurology group, more patients in the PIMS-TS neurology group were admitted to intensive care (20 [80%] of 25 patients vs six [22%] of 27 patients, p=0·0001) and received immunomodulatory treatment (22 [88%] patients vs 12 [44%] patients, p=0·045). 17 (33%) patients (10 [37%] in the COVID-19 neurology group and 7 [28%] in the PIMS-TS neurology group) were discharged with disability; one (2%) died (who had stroke, in the PIMS-TS neurology group).

Interpretation: This study identified key differences between those with a primary neurological disorder versus those with PIMS-TS. Compared with patients with a primary neurological disorder, more patients with PIMS-TS needed intensive care, but outcomes were similar overall. Further studies should investigate underlying mechanisms for neurological involvement in COVID-19 and the longer-term outcomes.

Funding: UK Research and Innovation, Medical Research Council, Wellcome Trust, National Institute for Health Research.

Figure 1

Study profile and classification of neurological disorders PIMS-TS=paediatric multisystem inflammatory syndrome temporally associated with COVID-19. ADEM=acute disseminated encephalomyelitis. MERS=mild encephalopathy with reversible splenial lesion. PRES=posterior reversible encephalopathy syndrome. *Recognised para-infectious or post-infectious syndromes. †All were encephalopathic. ‡Patients could have more than one feature.

Figure 2

MRI scans showing a range of neurological complications (A, B, C) MRI brain and spine scans from a White girl aged 2 years with ADEM (case number 4, appendix p 7; the full patient history is given in appendix p 1). There are multiple hyperintense foci on the axial T2-weighted (A) and T2 FLAIR (B) images involving both cerebral hemispheres, including the basal ganglia, thalami, and subcortical and periventricular white matter (green arrows). Sagittal T2-weighted image of the spine (C) shows a focus of hyperintensity within the cord close to the conus (red arrow). (D, E, F) MRI brain scans from an Asian boy aged 11 years who presented with PIMS-TS, encephalopathy, and MERS (case number 48, appendix p 11; the full patient history is given in appendix p 1). Axial T2-weighted image (D) shows a focus of hyperintensity involving the splenium of the corpus callosum along the midline (green arrow). The B1000 (E) and the ADC maps (F) from the diffusion-weighted imaging shows subtle diffusion restriction involving the lesion. (G, H, I, J) MRI spine scans from an Asian boy aged 16 months who presented with Guillain-Barré syndrome (case number 8, appendix p 7; the full patient history is given in appendix p 2). Sagittal T1-weighted images before (G) and after contrast (H) show enhancement of the lumbosacral nerve roots (green arrows). The axial T1-weighted post-contrast images (I, J) show bilateral enhancement of the nerve roots. ADEM=acute disseminated encephalomyelitis. FLAIR=fluid-attenuated inversion recovery. PIMS-TS=paediatric multisystem inflammatory syndrome temporally associated with COVID-19. MERS=mild encephalopathy with reversible splenial lesion. ADC=apparent diffusion coefficient.