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

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

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.

2352-4642
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McCrea, Nadine
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Ram, Dipak
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Ray, Stephen TJ
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Fuller, Charlotte
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Pysden, Karen
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Yoong, Michael
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McCullagh, Helen
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Scott, David
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Ray, Stephen TJ, Abdel-Mannan, Omar, Sa, Mario, Fuller, Charlotte, Wood, Greta K, Pysden, Karen, Yoong, Michael, McCullagh, Helen, Scott, David, McMahon, Martin, Thomas, Naomi, Taylor, Micheal, Marjorie, Illingworth, McCrea, Nadine, Davies, Victoria, Whitehouse, William, Zuberi, Sameer, Guthrie, Keira, Wassmer, Evangeline, Shah, Nikit, Baker, Mark R, Tiwary, Sangeeta, Tan, Hui Jeen, Varma, Uma, Ram, Dipak, Avula, Shivaram, Enright, Noelle, Hassell, Jane, Ross Russell, Amy, Kumar, Ram, Mulholland, Rachel E, Pett, Sarah, Galea, Ian, Thomas, Rhys H, Lim, Ming, Hacohen, Yael, Solomon, Tom, Griffiths, Michael J, Michael, Benedict D and Kneen, Rachel (2021) Neurological manifestations of SARS-CoV-2 infection in hospitalised children and adolescents in the UK: a prospective national cohort study. The Lancet Child & Adolescent Health. (doi:10.1016/S2352-4642(21)00193-0).

Record type: Article

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.

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Ray et al 2021_accepted - Accepted Manuscript
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Accepted/In Press date: 8 June 2021
e-pub ahead of print date: 15 July 2021
Published date: September 2021
Additional Information: BDM is supported for COVID-19 neuroscience research by UK Research and Innovation (UKRI) and the Medical Research Council (MRC; MR/V03605X/1); and for additional neurological inflammation due to viral infection research by grants from the MRC and UKRI (MR/V007181/1), MRC (MR/T028750/1), and the Wellcome Trust (ISSF201902/3). STJR is also supported by the Wellcome Trust for paediatric neuroinfectious research (203919/Z/16/Z). Ian Galea is supported by the National Institute for Health Research (NIHR). TS is supported by the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections (IS-HPU-1112-10117 and NIHR200907), NIHR Global Health Research Group on Brain Infections (17/63/110), the UK MRC Global Effort on COVID-19 Programme (MR/V033441/1), and the EU’s Horizon 2020 research and innovation programme (ZikaPLAN; 734584). MJG is supported for neuroscience and infection research internationally by MRC Newton Fund (MR/S019960/1), MRC Developmental Pathway Funding Scheme (MR/R015406/1), and NIHR (153195 17/60/67, 126156 17/63/11, and 200907)

Identifiers

Local EPrints ID: 450677
URI: http://eprints.soton.ac.uk/id/eprint/450677
ISSN: 2352-4642
PURE UUID: bb094df0-9990-4845-a1fb-86ae6c7f3c57
ORCID for Ian Galea: ORCID iD orcid.org/0000-0002-1268-5102

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Date deposited: 06 Aug 2021 16:30
Last modified: 17 Mar 2024 02:57

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Contributors

Author: Stephen TJ Ray
Author: Omar Abdel-Mannan
Author: Mario Sa
Author: Charlotte Fuller
Author: Greta K Wood
Author: Karen Pysden
Author: Michael Yoong
Author: Helen McCullagh
Author: David Scott
Author: Martin McMahon
Author: Naomi Thomas
Author: Micheal Taylor
Author: Illingworth Marjorie
Author: Nadine McCrea
Author: Victoria Davies
Author: William Whitehouse
Author: Sameer Zuberi
Author: Keira Guthrie
Author: Evangeline Wassmer
Author: Nikit Shah
Author: Mark R Baker
Author: Sangeeta Tiwary
Author: Hui Jeen Tan
Author: Uma Varma
Author: Dipak Ram
Author: Shivaram Avula
Author: Noelle Enright
Author: Jane Hassell
Author: Amy Ross Russell
Author: Ram Kumar
Author: Rachel E Mulholland
Author: Sarah Pett
Author: Ian Galea ORCID iD
Author: Rhys H Thomas
Author: Ming Lim
Author: Yael Hacohen
Author: Tom Solomon
Author: Michael J Griffiths
Author: Benedict D Michael
Author: Rachel Kneen

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