Spectrum, Risk Factors, and Outcomes of Neurological and Psychiatric Complications of COVID-19: A UK-Wide Cross-Sectional Surveillance Study

47 Pages Posted: 21 Jan 2021 Last revised: 24 Jun 2021

See all articles by Amy Ross Russell

Amy Ross Russell

University of Southampton

Marc Hardwick

University of Southampton

Athavan Jeyanantham

University of Southampton

Laura White

NHS Foundation Trust - Aintree University Hospital

Saumitro Deb

University of Liverpool

Girvan Burnside

University of Liverpool - Liverpool Clinical Trials Centre

Harriet Joy

University of Southampton - University Hospital Southampton NHS Foundation Trust

Craig Smith

University of Manchester

Tom Pollak

King's College London - Institute of Psychiatry, Psychology and Neuroscience

Timothy Nicholson

King's College London

Nicholas WS Davies

Chelsea and Westminster NHS Foundation Trust

Hadi Manji

University College London

Ava Easton

Encephalitis Society

Stephen Ray

University of Liverpool

Michael Zandi

University College London

Jonathan P Coles

University of Cambridge

David Menon

University of Cambridge - University Division of Anaesthesia

Aravinthan Varatharaj

University of Southampton

Beth McCausland

University of Southampton

Mark Ellul

University of Liverpool - Institute of Infection and Global Health

Naomi Thomas

Newcastle University

Gerome Breen

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

Stephen Keddie

UCL Institute of Neurology - Centre for Neuromuscular Disease

Michael Lunn

University College London

John PS Burn

NHS Foundation Trust - Poole

Graziella Quattrocchi

North Middlesex University Hospital

Luke Dixon

Imperial College Healthcare NHS Trust - Department of Neuroradiology

Claire M. Rice

Southmead Hospital - Department of Neurology

George Pengas

University Hospital Southampton NHS Foundation Trust - Wessex Neurological Centre - Department of Neurology

Rustam Al-Shahi Salman

University of Edinburgh

Alan Carson

University of Edinburgh

Eileen Joyce

University College London

Martin R Turner

University of Oxford

Laura Benjamin

University College London

Tom Solomon

University of Liverpool - Institute of Infection and Global Health

Rachel Kneen

University of Liverpool

Sarah Pett

University College London

Rhys H. Thomas

Newcastle University

Benedict Michael

University of Liverpool - Institute of Infection and Global Health; The Walton Centre NHS Foundation Trust; NIHR Health Protection Research Unit for Emerging and Zoonotic Infection

Ian Galea

University of Southampton

Date Written: January 17, 2021

Abstract

Background: SARS-CoV2 is associated with neurological and psychiatric complications including cerebrovascular events, encephalopathy and peripheral nerve disease. Detailed clinical data, including factors associated with recovery, is lacking, hampering prediction modelling and targeted therapeutic interventions. We studied COVID-associated neurological and psychiatric complications, to investigate the key clinical features, including those associated with outcome.

Methods: This UK-wide cross-sectional surveillance study of neurological and psychiatric complications of COVID-19 in adult hospitalised patients captured detailed data on demographics/risk factors, pre-COVID-19 Rockwood frailty score, comorbidities, neurological presentation and outcome. A priori clinical case definitions, based on criteria adopted by the World Health Organisation, were used, with cross-specialty independent adjudication for discrepant cases. Patients meeting multiple clinical case definitions were identified. Cases of stroke were compared to normative data during the equivalent time-period prior to the pandemic. Multivariable logistic regression was performed using demographic and clinical variables, to determine the factors associated with outcome.

Findings: 267 cases were included. Cerebrovascular events were most frequently reported (131, 49%), followed by central disorders (95, 36%) including delirium (28, 11%), central inflammatory (25, 9%), psychiatric (25, 9%), and other encephalopathies (17, 7%), including a severe encephalopathy not meeting delirium criteria; and peripheral nerve-disorders (41, 15%). 27% of cerebrovascular events occurred in patients <60 years. Relative to those >60 years old, the younger patients presented with delayed onset from respiratory symptoms, higher rates of multi-vessel occlusion (31%) and more frequently had systemic thrombotic events. Nevertheless, in both younger and older stroke cases there was an association with conventional, modifiable, cerebrovascular risk factors. The timing of neurological presentation varied between disease groups. In 34 cases (13%), clinical case definitions overlapped, and these cases were more likely to require intensive care and ventilation. Regardless of clinical case definition, older age, a higher pre-COVID-19 frailty score, and a high admission white cell count independently associated with a poor outcome. Limited recovery was most common for those with cerebrovascular events.

Interpretation: COVID-19 is associated with a broad spectrum of presentations throughout the nervous system, at varied time points relative to respiratory disease. Outcomes vary between disease groups, with cerebrovascular disease conferring the worst prognosis, but this effect was less marked than the pre-morbid factors of age and frailty. A severe encephalopathy occurs after COVID-19 and is associated with requiring intensive care and ventilation. COVID-19 is associated with large and multi-vessel stroke in young people, often with non-CNS thrombotic disease and requires further study. Nevertheless, conventional, modifiable risk factors were associated with stroke, even in younger people, suggesting the potential for public health intervention for this and future pandemics. These clinical data should be combined with blood and neuroimaging biomarkers so that patients can be stratified to targeted existing or novel therapeutics.

Note: Funding: UK Research and Innovation, Medical Research Council, and National Institute of Health Research

Declaration of Interests: None.

Ethics Approval Statement: The UK Health Research Authority advised that the study did not require review by an NHS Research Ethics Committee as this was a surveillance study with non-identifiable information. This study was approved by the University of Liverpool (UoL #7725/2020) and the University of Southampton (ERGO #56504).

Keywords: COVID-19, Coronavirus, Encephalitis, Encephalopathy, Stroke

Suggested Citation

Ross Russell, Amy and Hardwick, Marc and Jeyanantham, Athavan and White, Laura and Deb, Saumitro and Burnside, Girvan and Joy, Harriet and Smith, Craig and Pollak, Tom and Nicholson, Timothy and Davies, Nicholas WS and Manji, Hadi and Easton, Ava and Ray, Stephen and Zandi, Michael and Coles, Jonathan P and Menon, David and Varatharaj, Aravinthan and McCausland, Beth and Ellul, Mark and Thomas, Naomi and Breen, Gerome and Keddie, Stephen and Lunn, Michael and Burn, John PS and Quattrocchi, Graziella and Dixon, Luke and Rice, Claire M. and Pengas, George and Al-Shahi Salman, Rustam and Carson, Alan and Joyce, Eileen and Turner, Martin R and Benjamin, Laura and Solomon, Tom and Kneen, Rachel and Pett, Sarah and Thomas, Rhys H. and Michael, Benedict and Galea, Ian, Spectrum, Risk Factors, and Outcomes of Neurological and Psychiatric Complications of COVID-19: A UK-Wide Cross-Sectional Surveillance Study (January 17, 2021). Available at SSRN: https://ssrn.com/abstract=3767901 or http://dx.doi.org/10.2139/ssrn.3767901

Amy Ross Russell

University of Southampton ( email )

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

Marc Hardwick

University of Southampton ( email )

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

Athavan Jeyanantham

University of Southampton ( email )

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

Laura White

NHS Foundation Trust - Aintree University Hospital ( email )

United Kingdom

Saumitro Deb

University of Liverpool ( email )

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Girvan Burnside

University of Liverpool - Liverpool Clinical Trials Centre ( email )

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Harriet Joy

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

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

Craig Smith

University of Manchester ( email )

Oxford Road
Manchester, N/A M13 9PL
United Kingdom

Tom Pollak

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

London
United Kingdom

Timothy Nicholson

King's College London ( email )

Strand
London, England WC2R 2LS
United Kingdom

Nicholas WS Davies

Chelsea and Westminster NHS Foundation Trust ( email )

Hadi Manji

University College London ( email )

Gower Street
London, WC1E 6BT
United Kingdom

Ava Easton

Encephalitis Society ( email )

Stephen Ray

University of Liverpool ( email )

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Michael Zandi

University College London ( email )

Gower Street
London, WC1E 6BT
United Kingdom

Jonathan P Coles

University of Cambridge ( email )

Trinity Ln
Cambridge, CB2 1TN
United Kingdom

David Menon

University of Cambridge - University Division of Anaesthesia ( email )

United Kingdom

Aravinthan Varatharaj

University of Southampton ( email )

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

Beth McCausland

University of Southampton ( email )

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

Mark Ellul

University of Liverpool - Institute of Infection and Global Health ( email )

8 West Derby Street
Liverpool, L69 7BE
United Kingdom

Naomi Thomas

Newcastle University ( email )

Newcastle upon Tyne
NE1 7RU
United Kingdom

Gerome Breen

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

United Kingdom

Stephen Keddie

UCL Institute of Neurology - Centre for Neuromuscular Disease ( email )

Gower Street
London, WC1E 6BT
United Kingdom

Michael Lunn

University College London ( email )

Gower Street
London, WC1E 6BT
United Kingdom

John PS Burn

NHS Foundation Trust - Poole

Longfleet Rd
Poole BH15 2JB
United Kingdom

Graziella Quattrocchi

North Middlesex University Hospital

London
United Kingdom

Luke Dixon

Imperial College Healthcare NHS Trust - Department of Neuroradiology

Praed St
London
United Kingdom

Claire M. Rice

Southmead Hospital - Department of Neurology

Southmead Rd
Westbury-on-Trym
Bristol, BS10 5NB
United Kingdom

George Pengas

University Hospital Southampton NHS Foundation Trust - Wessex Neurological Centre - Department of Neurology

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

Rustam Al-Shahi Salman

University of Edinburgh ( email )

Old College
South Bridge
Edinburgh, Scotland EH8 9JY
United Kingdom

Alan Carson

University of Edinburgh ( email )

Old College
South Bridge
Edinburgh, Scotland EH8 9JY
United Kingdom

Eileen Joyce

University College London ( email )

Gower Street
London, WC1E 6BT
United Kingdom

Martin R Turner

University of Oxford ( email )

Mansfield Road
Oxford, Oxfordshire OX1 4AU
United Kingdom

Laura Benjamin

University College London ( email )

Gower Street
London, WC1E 6BT
United Kingdom

Tom Solomon

University of Liverpool - Institute of Infection and Global Health ( email )

8 West Derby Street
Liverpool, L69 7BE
United Kingdom

Rachel Kneen

University of Liverpool ( email )

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Sarah Pett

University College London ( email )

Gower Street
London, WC1E 6BT
United Kingdom

Rhys H. Thomas

Newcastle University ( email )

Newcastle upon Tyne
NE1 7RU
United Kingdom

Benedict Michael

University of Liverpool - Institute of Infection and Global Health ( email )

8 West Derby Street
Liverpool, L69 7BE
United Kingdom

The Walton Centre NHS Foundation Trust ( email )

NIHR Health Protection Research Unit for Emerging and Zoonotic Infection ( email )

Ian Galea (Contact Author)

University of Southampton ( email )

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

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