The University of Southampton
University of Southampton Institutional Repository
Warning ePrints Soton is experiencing an issue with some file downloads not being available. We are working hard to fix this. Please bear with us.

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
Ray, Stephen TJ
c2c97be0-236d-474e-977c-b3f48d989330
Abdel-Mannan, Omar
71786b85-2361-4dfb-b0e5-766895805369
Sa, Mario
972a6cee-96bd-494b-a133-4223d4b0fa3a
Fuller, Charlotte
e9785255-47e2-43e5-bc0e-b44e4c19f2c8
Wood, Greta K
2a6007e7-86ef-4959-8929-e69ce646b8e1
Pysden, Karen
1409008e-8006-436e-a495-0694ebe2bc6a
Yoong, Michael
072b894e-6414-48e2-a05e-e69beb8003b4
McCullagh, Helen
450609b4-8884-4b9f-9435-dc9f74243fc2
Scott, David
4f47b8c1-5f9c-42a3-b046-72512a209cca
McMahon, Martin
96fb4350-cfa8-4207-b83f-9a8e2f6bd959
Thomas, Naomi
0fda5a81-f92f-4703-9e0a-d2cf6cf02267
Taylor, Micheal
0421ad5c-6870-4f77-ba0b-991c68976dca
Marjorie, Illingworth
8672e77d-81d0-4272-91c7-babc0d9f439a
McCrea, Nadine
147f7384-22b4-4a85-8394-ef6727a34a62
Davies, Victoria
2e451333-5718-47d6-a4ae-03f8a4b06f15
Whitehouse, William
5cede507-72cf-41cd-963d-1b7cce61fed5
Zuberi, Sameer
f909ca9d-b2bb-4cc0-9d36-38059c70e8ee
Guthrie, Keira
47bc156b-7b68-47af-837e-5d5cae9f9d70
Wassmer, Evangeline
9ce66ff0-5bbf-4f56-ad31-07501c1f3347
Shah, Nikit
fb7c676d-6394-4792-acee-142fd0e7b884
Baker, Mark R
1adeeeb7-d0ff-43e4-bb0f-d4947df0330b
Tiwary, Sangeeta
f0674a4f-cdb1-4d41-8514-32e8effd260a
Tan, Hui Jeen
fe3ebba1-912d-464d-9ca4-8d2c5a514ca9
Varma, Uma
fd40be4e-51e3-4104-874f-fb01bd6dd9e9
Ram, Dipak
c296dcfe-3146-42a6-acc2-2a2e325ba3ed
Avula, Shivaram
502165bb-db78-4042-8da5-636315217511
Enright, Noelle
d0f66e89-b83c-4288-b5d4-b974db333126
Hassell, Jane
ba982a15-c159-4eea-a35b-5ff9dfa95adb
Ross Russell, Amy
b99087ed-1439-45a7-97fe-6ab67c3ea29f
Kumar, Ram
5dc8ed4a-6d04-480a-99c0-b3e6392fb8b7
Mulholland, Rachel E
865d9969-13a2-4da4-b5c9-0eff1c2536b2
Pett, Sarah
668723db-c376-4852-a389-c5bf840d9edd
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Thomas, Rhys H
76c90c44-42ab-4f2a-b98b-d06a373fd66f
Lim, Ming
919de454-96b6-4340-a9e6-831f499e4c8f
Hacohen, Yael
8e2381f6-3af3-43a4-884e-bf1a4b94a666
Solomon, Tom
3311a8fe-fc3d-42ab-8c99-cacc179f1f77
Griffiths, Michael J
68c81945-ea8b-4eac-8de5-c58ee1ee262e
Michael, Benedict D
a8e132be-ebd8-422d-a015-d419eaf89845
Kneen, Rachel
4425de52-d7eb-4abc-b416-84c908d4852e
Ray, Stephen TJ
c2c97be0-236d-474e-977c-b3f48d989330
Abdel-Mannan, Omar
71786b85-2361-4dfb-b0e5-766895805369
Sa, Mario
972a6cee-96bd-494b-a133-4223d4b0fa3a
Fuller, Charlotte
e9785255-47e2-43e5-bc0e-b44e4c19f2c8
Wood, Greta K
2a6007e7-86ef-4959-8929-e69ce646b8e1
Pysden, Karen
1409008e-8006-436e-a495-0694ebe2bc6a
Yoong, Michael
072b894e-6414-48e2-a05e-e69beb8003b4
McCullagh, Helen
450609b4-8884-4b9f-9435-dc9f74243fc2
Scott, David
4f47b8c1-5f9c-42a3-b046-72512a209cca
McMahon, Martin
96fb4350-cfa8-4207-b83f-9a8e2f6bd959
Thomas, Naomi
0fda5a81-f92f-4703-9e0a-d2cf6cf02267
Taylor, Micheal
0421ad5c-6870-4f77-ba0b-991c68976dca
Marjorie, Illingworth
8672e77d-81d0-4272-91c7-babc0d9f439a
McCrea, Nadine
147f7384-22b4-4a85-8394-ef6727a34a62
Davies, Victoria
2e451333-5718-47d6-a4ae-03f8a4b06f15
Whitehouse, William
5cede507-72cf-41cd-963d-1b7cce61fed5
Zuberi, Sameer
f909ca9d-b2bb-4cc0-9d36-38059c70e8ee
Guthrie, Keira
47bc156b-7b68-47af-837e-5d5cae9f9d70
Wassmer, Evangeline
9ce66ff0-5bbf-4f56-ad31-07501c1f3347
Shah, Nikit
fb7c676d-6394-4792-acee-142fd0e7b884
Baker, Mark R
1adeeeb7-d0ff-43e4-bb0f-d4947df0330b
Tiwary, Sangeeta
f0674a4f-cdb1-4d41-8514-32e8effd260a
Tan, Hui Jeen
fe3ebba1-912d-464d-9ca4-8d2c5a514ca9
Varma, Uma
fd40be4e-51e3-4104-874f-fb01bd6dd9e9
Ram, Dipak
c296dcfe-3146-42a6-acc2-2a2e325ba3ed
Avula, Shivaram
502165bb-db78-4042-8da5-636315217511
Enright, Noelle
d0f66e89-b83c-4288-b5d4-b974db333126
Hassell, Jane
ba982a15-c159-4eea-a35b-5ff9dfa95adb
Ross Russell, Amy
b99087ed-1439-45a7-97fe-6ab67c3ea29f
Kumar, Ram
5dc8ed4a-6d04-480a-99c0-b3e6392fb8b7
Mulholland, Rachel E
865d9969-13a2-4da4-b5c9-0eff1c2536b2
Pett, Sarah
668723db-c376-4852-a389-c5bf840d9edd
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Thomas, Rhys H
76c90c44-42ab-4f2a-b98b-d06a373fd66f
Lim, Ming
919de454-96b6-4340-a9e6-831f499e4c8f
Hacohen, Yael
8e2381f6-3af3-43a4-884e-bf1a4b94a666
Solomon, Tom
3311a8fe-fc3d-42ab-8c99-cacc179f1f77
Griffiths, Michael J
68c81945-ea8b-4eac-8de5-c58ee1ee262e
Michael, Benedict D
a8e132be-ebd8-422d-a015-d419eaf89845
Kneen, Rachel
4425de52-d7eb-4abc-b416-84c908d4852e

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.

Text
Ray et al 2021_accepted - Accepted Manuscript
Download (957kB)

More information

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

Catalogue record

Date deposited: 06 Aug 2021 16:30
Last modified: 15 Oct 2021 01:38

Export record

Altmetrics

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

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×