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

36 Pages Posted: 12 May 2021

See all articles by Stephen T.J. Ray

Stephen T.J. Ray

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences

Omar Abdel-Mannan

Great Ormond Street - Department of Paediatric Neurology

Mario Sa

Guy's and St Thomas' NHS Foundation Trust - Evelina London Children's Hospital

Charlotte Fuller

Leeds Teaching Hospitals NHS Trust

Greta K. Wood

University of Liverpool - Institute of Infection and Global Health

Karen Psyden

Leeds Teaching Hospitals NHS Trust

Michael Yoong

Government of the United Kingdom - Barts Health NHS Trust

S. Ramas

Oxford Children’s Hospital - Paediatric Neurology Department

Helen McCullagh

Leeds Teaching Hospitals NHS Trust

D. Scott

Leeds Community Healthcare Trust - Child and Adolescent Mental Health Services

M. McMahon

Leeds Community Healthcare Trust - Child and Adolescent Mental Health Services

Naomi Thomas

Newcastle University

M. Taylor

Leeds Teaching Hospitals NHS Trust

Brigitte Vollmer

University of Southampton - Southampton Children’s Hospital

Marjorie Illingworth

University of Southampton - Southampton Children’s Hospital

Nadine McCrea

Oxford Children’s Hospital - Paediatric Neurology Department

Victoria Davies

Nottingham Children's Hospital

William Whitehouse

Nottingham Children's Hospital

S. Zuberi

Royal Hospital for Children; Royal Hospital for Children

Keira Guthrie

Royal Hospital for Children

Evangeline Wassmer

Birmingham Children’s Hospital - Department of Neurology

N. Shah

Birmingham Children's Hospital - Department of Neurology

Mark R. Baker

University of Newcastle - Newcastle University Translational and Clinical Research Institute

Sangeeta Tiwary

Northumbria Healthcare NHS Foundation Trust

Christina Petropoulos

University Hospital London - Paediatrics Department

Victoria Vlachou

Government of the United Kingdom, Department of Health, National Health Service (NHS), Chelsea and Westminster Hospital

Maria Kinali

Imperial College London

H. Jeen Tan

Royal Manchester Children’s Hospital - Department of Neurology

Uma Varma

Royal Manchester Children’s Hospital - Department of Neurology

Dipak Ram

Royal Manchester Children’s Hospital - Department of Neurology

Shivaram Avula

Alder Hey Children's NHS Foundation Trust

Gerome Breen

King's College London - Institute of Psychiatry, Psychology & Neuroscience (IoPPN)

Noelle Enright

Great Ormond Street Hospital for Children

Jane Hassell

Great Ormond Street Hospital - Department of Paediatric Infectious Diseases

Amy L. Ross Russell

University of Southampton - University Hospital Southampton NHS Foundation Trust

R. Kumar

Alder Hey Children's NHS Foundation Trust

Rachel E. Mulholland

Alder Hey Children's NHS Foundation Trust

Sarah Pett

University College London

Ian Galea

University of Southampton

Rhys H. Thomas

Newcastle University

Ming Lim

Guy's and St Thomas' NHS Foundation Trust - Children's Neuroscience Centre

Yael Hacohen

Great Ormond Street - Department of Paediatric Neurology

T. Solomon

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences

Michael John Griffiths

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences

B.D. Michael

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences

Rachel Kneen

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences; Alder Hey Children's NHS Foundation Trust

CoroNerve Studies Group

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Abstract

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-Barré 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.

Suggested Citation

Ray, Stephen T.J. and Abdel-Mannan, Omar and Sa, Mario and Fuller, Charlotte and Wood, Greta K. and Psyden, Karen and Yoong, Michael and Ramas, S. and McCullagh, Helen and Scott, D. and McMahon, M. and Thomas, Naomi and Taylor, M. and Vollmer, Brigitte and Illingworth, Marjorie and McCrea, Nadine and Davies, Victoria and Whitehouse, William and Zuberi, S. and Guthrie, Keira and Wassmer, Evangeline and Shah, N. and Baker, Mark R. and Tiwary, Sangeeta and Petropoulos, Christina and Vlachou, Victoria and Kinali, Maria and Tan, H. Jeen and Varma, Uma and Ram, Dipak and Avula, Shivaram and Breen, Gerome and Enright, Noelle and Hassell, Jane and Ross Russell, Amy L. and Kumar, R. and Mulholland, Rachel E. and Pett, Sarah and Galea, Ian and Thomas, Rhys H. and Lim, Ming and Hacohen, Yael and Solomon, T. and Griffiths, Michael John and Michael, B.D. and Kneen, Rachel and Group, CoroNerve Studies, Neurological and Psychiatric Manifestations of COVID-19 in UK Children: A Prospective National Cohort Study. Available at SSRN: https://ssrn.com/abstract=3844784 or http://dx.doi.org/10.2139/ssrn.3844784

Stephen T.J. Ray

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences ( email )

Liverpool
United Kingdom

Omar Abdel-Mannan

Great Ormond Street - Department of Paediatric Neurology ( email )

Great Ormond St
London, WC1N 3JH
United Kingdom

Mario Sa

Guy's and St Thomas' NHS Foundation Trust - Evelina London Children's Hospital ( email )

London
United Kingdom

Charlotte Fuller

Leeds Teaching Hospitals NHS Trust ( email )

United Kingdom

Greta K. Wood

University of Liverpool - Institute of Infection and Global Health

8 West Derby Street
Liverpool, L69 7BE
United Kingdom

Karen Psyden

Leeds Teaching Hospitals NHS Trust ( email )

United Kingdom

Michael Yoong

Government of the United Kingdom - Barts Health NHS Trust ( email )

London, E1 1BB
United Kingdom

S. Ramas

Oxford Children’s Hospital - Paediatric Neurology Department

Oxford
United Kingdom

Helen McCullagh

Leeds Teaching Hospitals NHS Trust ( email )

Leeds
United Kingdom

D. Scott

Leeds Community Healthcare Trust - Child and Adolescent Mental Health Services

Leeds
United Kingdom

M. McMahon

Leeds Community Healthcare Trust - Child and Adolescent Mental Health Services

Leeds
United Kingdom

Naomi Thomas

Newcastle University ( email )

Newcastle upon Tyne
NE1 7RU
United Kingdom

M. Taylor

Leeds Teaching Hospitals NHS Trust

United Kingdom

Brigitte Vollmer

University of Southampton - Southampton Children’s Hospital ( email )

Southampton
United Kingdom

Marjorie Illingworth

University of Southampton - Southampton Children’s Hospital ( email )

Southampton
United Kingdom

Nadine McCrea

Oxford Children’s Hospital - Paediatric Neurology Department ( email )

Oxford
United Kingdom

Victoria Davies

Nottingham Children's Hospital ( email )

United Kingdom

William Whitehouse

Nottingham Children's Hospital ( email )

United Kingdom

S. Zuberi

Royal Hospital for Children

Glasgow, Scotland
United Kingdom

Royal Hospital for Children

Glasgow, Scotland
United Kingdom

Keira Guthrie

Royal Hospital for Children ( email )

Glasgow, Scotland
United Kingdom

Evangeline Wassmer

Birmingham Children’s Hospital - Department of Neurology ( email )

Birmingham
United Kingdom

N. Shah

Birmingham Children's Hospital - Department of Neurology

Birmingham
United Kingdom

Mark R. Baker

University of Newcastle - Newcastle University Translational and Clinical Research Institute ( email )

Newcastle
United Kingdom

Sangeeta Tiwary

Northumbria Healthcare NHS Foundation Trust ( email )

Newcastle
United Kingdom

Christina Petropoulos

University Hospital London - Paediatrics Department ( email )

London
United Kingdom

Victoria Vlachou

Government of the United Kingdom, Department of Health, National Health Service (NHS), Chelsea and Westminster Hospital ( email )

United Kingdom

Maria Kinali

Imperial College London ( email )

South Kensington Campus
Exhibition Road
London, SW7 2AZ
United Kingdom

H. Jeen Tan

Royal Manchester Children’s Hospital - Department of Neurology ( email )

Manchester
United Kingdom

Uma Varma

Royal Manchester Children’s Hospital - Department of Neurology ( email )

Manchester
United Kingdom

Dipak Ram

Royal Manchester Children’s Hospital - Department of Neurology ( email )

Manchester
United Kingdom

Shivaram Avula

Alder Hey Children's NHS Foundation Trust ( email )

Liverpool
United Kingdom

Gerome Breen

King's College London - Institute of Psychiatry, Psychology & Neuroscience (IoPPN) ( email )

United Kingdom

Noelle Enright

Great Ormond Street Hospital for Children ( email )

London
United Kingdom

Jane Hassell

Great Ormond Street Hospital - Department of Paediatric Infectious Diseases ( email )

London
United Kingdom

Amy L. Ross Russell

University of Southampton - University Hospital Southampton NHS Foundation Trust ( email )

University Rd.
Southampton SO17 1BJ, Hampshire SO17 1LP
United Kingdom

R. Kumar

Alder Hey Children's NHS Foundation Trust

Liverpool
United Kingdom

Rachel E. Mulholland

Alder Hey Children's NHS Foundation Trust ( email )

Liverpool
United Kingdom

Sarah Pett

University College London ( email )

Gower Street
London, WC1E 6BT
United Kingdom

Ian Galea

University of Southampton ( email )

University Rd.
Southampton SO17 1BJ, Hampshire SO17 1LP
United Kingdom

Rhys H. Thomas

Newcastle University ( email )

Newcastle upon Tyne
NE1 7RU
United Kingdom

Ming Lim

Guy's and St Thomas' NHS Foundation Trust - Children's Neuroscience Centre ( email )

London
United Kingdom

Yael Hacohen

Great Ormond Street - Department of Paediatric Neurology ( email )

Great Ormond St
London, WC1N 3JH
United Kingdom

T. Solomon

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences

United Kingdom

Michael John Griffiths

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences ( email )

United Kingdom

B.D. Michael

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences

United Kingdom

Rachel Kneen (Contact Author)

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences ( email )

Liverpool
United Kingdom

Alder Hey Children's NHS Foundation Trust

Liverpool
United Kingdom

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