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

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

doi:10.1093/braincomms/fcab168

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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

32 Citations (Scopus)

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.

Original language	English
Article number	fcab168
Journal	Brain Communications
Volume	3
Issue number	3
DOIs	https://doi.org/10.1093/braincomms/fcab168
Publication status	Published - 2021

Keywords

COVID-19
encephalopathy
neurology
SARS-CoV-2
stroke

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/braincomms/fcab168

Cite this

Ross Russell, A. L., Hardwick, M., Jeyanantham, A., White, L. M., Deb, S., Burnside, G., Joy, H. M., Smith, C. J., Pollak, T. A., Nicholson, T. R., Davies, N. W. S., Manji, H., Easton, A., Ray, S., Zandi, M. S., Coles, J. P., Menon, D. K., Varatharaj, A., Mccausland, B., ... Galea, I. (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), Article fcab168. https://doi.org/10.1093/braincomms/fcab168

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

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. ",

keywords = "COVID-19, encephalopathy, neurology, SARS-CoV-2, stroke",

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

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.",

year = "2021",

doi = "10.1093/braincomms/fcab168",

language = "English",

volume = "3",

journal = "Brain Communications",

issn = "2632-1297",

publisher = "Oxford University Press",

number = "3",

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Ross Russell, AL, Hardwick, M, Jeyanantham, A, White, LM, Deb, S, Burnside, G, Joy, HM, Smith, CJ, Pollak, TA , Nicholson, TR, Davies, NWS, Manji, H, Easton, A, Ray, S, Zandi, MS, Coles, JP, Menon, DK, Varatharaj, A, Mccausland, B, Ellul, MA, Thomas, N, Breen, G, Keddie, S, Lunn, MP, Burn, JPS, Quattrocchi, G, Dixon, L, Rice, CM, Pengas, G, Al-Shahi Salman, R, Carson, A, Joyce, EM, Turner, MR, Benjamin, LA, Solomon, T, Kneen, R, Pett, S, Thomas, RH, Michael, BD & Galea, I 2021, 'Spectrum, risk factors and outcomes of neurological and psychiatric complications of COVID-19: a UK-wide cross-sectional surveillance study', Brain Communications, vol. 3, no. 3, fcab168. https://doi.org/10.1093/braincomms/fcab168

TY - JOUR

T1 - Spectrum, risk factors and outcomes of neurological and psychiatric complications of COVID-19

T2 - a UK-wide cross-sectional surveillance study

AU - Ross Russell, Amy L.

AU - Hardwick, Marc

AU - Jeyanantham, Athavan

AU - White, Laura M.

AU - Deb, Saumitro

AU - Burnside, Girvan

AU - Joy, Harriet M.

AU - Smith, Craig J.

AU - Pollak, Thomas A.

AU - Nicholson, Timothy R.

AU - Davies, Nicholas W.S.

AU - Manji, Hadi

AU - Easton, Ava

AU - Ray, Stephen

AU - Zandi, Michael S.

AU - Coles, Jonathan P.

AU - Menon, David K.

AU - Varatharaj, Aravinthan

AU - Mccausland, Beth

AU - Ellul, Mark A.

AU - Thomas, Naomi

AU - Breen, Gerome

AU - Keddie, Stephen

AU - Lunn, Michael P.

AU - Burn, John P.S.

AU - Quattrocchi, Graziella

AU - Dixon, Luke

AU - Rice, Claire M.

AU - Pengas, George

AU - Al-Shahi Salman, Rustam

AU - Carson, Alan

AU - Joyce, Eileen M.

AU - Turner, Martin R.

AU - Benjamin, Laura A.

AU - Solomon, Tom

AU - Kneen, Rachel

AU - Pett, Sarah

AU - Thomas, Rhys H.

AU - Michael, Benedict D.

AU - Galea, Ian

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - COVID-19

KW - encephalopathy

KW - neurology

KW - SARS-CoV-2

KW - stroke

UR - http://www.scopus.com/inward/record.url?scp=85137615323&partnerID=8YFLogxK

U2 - 10.1093/braincomms/fcab168

DO - 10.1093/braincomms/fcab168

M3 - Article

AN - SCOPUS:85137615323

SN - 2632-1297

VL - 3

JO - Brain Communications

JF - Brain Communications

IS - 3

M1 - fcab168

ER -

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

Abstract

Keywords

UN SDGs

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