Neurological and Psychiatric Manifestations of COVID-19 in UK Children: A Prospective National Cohort Study

Background: The spectrum of neurological and psychiatric complications associated with COVID-19 is poorly understood in children. Methods: Children and adolescents (<18 years) with neurological or psychiatric disorders were included if paediatric neurologists considered SARS-CoV-2 infection to be relevant to the presentation. Cases were classified as having either a primary COVID-19 neurological/psychiatric disorder or as being associated with Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS). The denominator of all hospitalised children with COVID-19 was collated from National Health Service England data. Findings: Fifty-two cases were identified, among 1334 children hospitalised with COVID-19 giving an estimated incidence of 3.8 per 100 children. Twenty-seven (52%) had a primary neurological or psychiatric disorder, 25 (48%) had features associated with PIMS-TS. The median (range) age was 9 (1-17) years. Thirty-six (69%) were from Black or Asian backgrounds. In the primary neurology/psychiatry disorder group, diagnoses included seven with status epilepticus, five encephalitis, five Guillain-Barre syndrome, three acute demyelinating syndromes, two chorea, two psychosis, two encephalopathy, one transient ischaemic attack. The PIMS-TS neurology group more often had multiple features, which included encephalopathy (22, 88%), peripheral nervous system involvement (10, 40%), behavioural change (9, 36%), hallucinations (6, 24%). A recognised neuro-immune disorder was more common in the primary neurology than the PIMS-TS neurology group (13/27 [48%] vs 1/25 [0.04%], p=0.0003). More patients in the PIMS-TS neurology group were admitted to intensive care (20/25 [80%] vs 6/27 [22%], p=0.0001) and received immunomodulatory treatment (22/25 [88%] vs 12/27 [44%]), p=0.045). Seventeen (33%) were discharged with disability; one PIMS-TS child with stroke died. Interpretation: This first nation-wide study of the neurological and psychiatric manifestations of COVID-19 in children identified key differences between those with a primary disorder versus those with PIMS-TS. More PIMS-TS children needed intensive care, but outcomes were similar overall. Further studies must investigate underlying mechanisms and longer-term outcomes. Funding Statement: BDM and GB are supported to conduct COVID-19 neuroscience research by the UKRI/MRC (MR/V03605X/1); for additional neurological inflammation research due to viral infection BDM is also supported by grants from the MRC/UKRI (MR/V007181//1), MRC (MR/T028750/1) and Wellcome (ISSF201902/3). SR is also supported by Wellcome to conduct paediatric neuroinfectious research (203919/Z/16/Z). IG is supported by NIHR. TS is supported by the National Institute for Health Research (NIHR) Health Protection Research Unit in Emerging and Zoonotic Infections (Grant Nos. IS-HPU-1112-10117 and NIHR200907), NIHR Global Health Research Group on Brain Infections (No. 17/63/110), the UK Medical Research Council’s Global Effort on COVID-19 Programme (MR/V033441/1), and the European Union's Horizon 2020 research and innovation program ZikaPLAN (Preparedness Latin America Network), grant agreement No. 734584. MG is supported to conduct neuroscience and infection research internationally by MRC Newton Fund (MR/S019960/1), MRC DPFS (MR/R015406/1) and NIHR (153195 17/60/67, 126156 17/63/11 and 200907). Declaration of Interests: None. Ethics Approval Statement: The study was approved by the University of Liverpool Institute of Infection Veterinary and Ecological Sciences Ethics Committee (UoL #7725/2020) and the University of Southampton Faculty of Medicine Ethics Committee (ERGO #56504). The electronic CRF was hosted on ALEA (www.aleaclinical.eu) and managed by the Clinical Information Research Unit.