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Spectrum, risk factors, and outcomes of neurological and psychiatric complications of COVID-19: a UK-wide cross-sectional surveillance study

Spectrum, risk factors, and outcomes of neurological and psychiatric complications of COVID-19: a UK-wide cross-sectional surveillance study
Spectrum, risk factors, and outcomes of neurological and psychiatric complications of COVID-19: a UK-wide cross-sectional surveillance study

SARS-CoV-2 is associated with new-onset neurological and psychiatric conditions. Detailed clinical data, including factors associated with recovery, are lacking, hampering prediction modelling and targeted therapeutic interventions. In a UK-wide cross-sectional surveillance study of adult hospitalized patients during the first COVID-19 wave, with multi-professional input from general and sub-specialty neurologists, psychiatrists, stroke physicians, and intensivists, we captured detailed data on demographics, risk factors, pre-COVID-19 Rockwood frailty score, comorbidities, neurological presentation and outcome. A priori clinical case definitions were used, with cross-specialty independent adjudication for discrepant cases. Multivariable logistic regression was performed using demographic and clinical variables, to determine the factors associated with outcome. A total of 267 cases were included. Cerebrovascular events were most frequently reported (131, 49%), followed by other central disorders (95, 36%) including delirium (28, 11%), central inflammatory (25, 9%), psychiatric (25, 9%), and other encephalopathies (17, 7%), including a severe encephalopathy ( n  = 13) not meeting delirium criteria; and peripheral nerve disorders (41, 15%). Those with the severe encephalopathy, in comparison to delirium, were younger, had higher rates of admission to intensive care and a longer duration of ventilation. Compared to normative data during the equivalent time period prior to the pandemic, cases of stroke in association with COVID-19 were younger and had a greater number of conventional, modifiable cerebrovascular risk factors. Twenty-seven per cent of strokes occurred in patients <60 years. Relative to those >60 years old, the younger stroke patients presented with delayed onset from respiratory symptoms, higher rates of multi-vessel occlusion (31%) and systemic thrombotic events. Clinical outcomes varied between disease groups, with cerebrovascular disease conferring the worst prognosis, but this effect was less marked than the pre-morbid factors of older age and a higher pre-COVID-19 frailty score, and a high admission white cell count, which were independently associated with a poor outcome. In summary, this study describes the spectrum of neurological and psychiatric conditions associated with COVID-19. In addition, we identify a severe COVID-19 encephalopathy atypical for delirium, and a phenotype of COVID-19 associated stroke in younger adults with a tendency for multiple infarcts and systemic thromboses. These clinical data will be useful to inform mechanistic studies and stratification of patients in clinical trials.

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Ross Russell, Amy L, Hardwick, Marc, Jeyanantham, Athavan, White, Laura M, Deb, Saumitro, Burnside, Girvan, Joy, Harriet, Smith, Craig J, Pollak, Thomas A, Nicholson, Timothy R, Davies, Nicholas WS, Manji, Hadi, Easton, Ava, Ray, Stephen, Zandi, Michael S, Coles, Jonathan P., Menon, David K., Varatharaj, Aravinthan, Mccausland, Beth, Ellul, Mark A, Thomas, Naomi, Breen, Gerome, Keddie, Stephen, Lunn, Michael P, Burn, John PS, Quattrocchi, Graziella, Dixon, Luke, Rice, Claire M, Pengas, George, Al-Shahi Salman, Rustam, Carson, Alan, Joyce, Eileen M., Turner, Martin R, Benjamin, Laura A, Solomon, Tom, Kneen, Rachel, Pett, Sarah, Thomas, Rhys H, Michael, Benedict D and Galea, Ian (2021) Spectrum, risk factors, and outcomes of neurological and psychiatric complications of COVID-19: a UK-wide cross-sectional surveillance study. Brain Communications, 3 (3), fcab168. (doi:10.1093/braincomms/fcab168).

Record type: Article

Abstract

SARS-CoV-2 is associated with new-onset neurological and psychiatric conditions. Detailed clinical data, including factors associated with recovery, are lacking, hampering prediction modelling and targeted therapeutic interventions. In a UK-wide cross-sectional surveillance study of adult hospitalized patients during the first COVID-19 wave, with multi-professional input from general and sub-specialty neurologists, psychiatrists, stroke physicians, and intensivists, we captured detailed data on demographics, risk factors, pre-COVID-19 Rockwood frailty score, comorbidities, neurological presentation and outcome. A priori clinical case definitions were used, with cross-specialty independent adjudication for discrepant cases. Multivariable logistic regression was performed using demographic and clinical variables, to determine the factors associated with outcome. A total of 267 cases were included. Cerebrovascular events were most frequently reported (131, 49%), followed by other central disorders (95, 36%) including delirium (28, 11%), central inflammatory (25, 9%), psychiatric (25, 9%), and other encephalopathies (17, 7%), including a severe encephalopathy ( n  = 13) not meeting delirium criteria; and peripheral nerve disorders (41, 15%). Those with the severe encephalopathy, in comparison to delirium, were younger, had higher rates of admission to intensive care and a longer duration of ventilation. Compared to normative data during the equivalent time period prior to the pandemic, cases of stroke in association with COVID-19 were younger and had a greater number of conventional, modifiable cerebrovascular risk factors. Twenty-seven per cent of strokes occurred in patients <60 years. Relative to those >60 years old, the younger stroke patients presented with delayed onset from respiratory symptoms, higher rates of multi-vessel occlusion (31%) and systemic thrombotic events. Clinical outcomes varied between disease groups, with cerebrovascular disease conferring the worst prognosis, but this effect was less marked than the pre-morbid factors of older age and a higher pre-COVID-19 frailty score, and a high admission white cell count, which were independently associated with a poor outcome. In summary, this study describes the spectrum of neurological and psychiatric conditions associated with COVID-19. In addition, we identify a severe COVID-19 encephalopathy atypical for delirium, and a phenotype of COVID-19 associated stroke in younger adults with a tendency for multiple infarcts and systemic thromboses. These clinical data will be useful to inform mechanistic studies and stratification of patients in clinical trials.

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Accepted/In Press date: 27 May 2021
Published date: 22 July 2021
Additional Information: First author, Amy L. Ross Russell affiliates to NIHR Southampton CRF and BRC but has no internal profile in Pure, hence, these added as Organisational Units

Identifiers

Local EPrints ID: 450514
URI: http://eprints.soton.ac.uk/id/eprint/450514
ISSN: 2632-1297
PURE UUID: 70ae2269-de19-4e9a-93bd-bb9254a588b4
ORCID for Aravinthan Varatharaj: ORCID iD orcid.org/0000-0003-1629-5774
ORCID for Ian Galea: ORCID iD orcid.org/0000-0002-1268-5102

Catalogue record

Date deposited: 02 Aug 2021 16:31
Last modified: 12 Nov 2021 03:06

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Contributors

Author: Amy L Ross Russell
Author: Marc Hardwick
Author: Athavan Jeyanantham
Author: Laura M White
Author: Saumitro Deb
Author: Girvan Burnside
Author: Harriet Joy
Author: Craig J Smith
Author: Thomas A Pollak
Author: Timothy R Nicholson
Author: Nicholas WS Davies
Author: Hadi Manji
Author: Ava Easton
Author: Stephen Ray
Author: Michael S Zandi
Author: Jonathan P. Coles
Author: David K. Menon
Author: Beth Mccausland
Author: Mark A Ellul
Author: Naomi Thomas
Author: Gerome Breen
Author: Stephen Keddie
Author: Michael P Lunn
Author: John PS Burn
Author: Graziella Quattrocchi
Author: Luke Dixon
Author: Claire M Rice
Author: George Pengas
Author: Rustam Al-Shahi Salman
Author: Alan Carson
Author: Eileen M. Joyce
Author: Martin R Turner
Author: Laura A Benjamin
Author: Tom Solomon
Author: Rachel Kneen
Author: Sarah Pett
Author: Rhys H Thomas
Author: Benedict D Michael
Author: Ian Galea ORCID iD

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