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

Ross Russell, A.L. and Hardwick, M. and Jeyanantham, A. and White, L.M. and Deb, S. and Burnside, G. and Joy, H.M. and Smith, C.J. and Pollak, T.A. and Nicholson, T.R. and Davies, N.W.S. and Manji, H. and Easton, A. and Ray, S. and Zandi, M.S. and Coles, J.P. and Menon, D.K. and Varatharaj, A. and Mccausland, B. and Ellul, M.A. and Thomas, N. and Breen, G. and Keddie, S. and Lunn, M.P. and Burn, J.P.S. and Quattrocchi, G. and Dixon, L. and Rice, C.M. and Pengas, G. and Al-Shahi Salman, R. and Carson, A. and Joyce, E.M. and Turner, M.R. and Benjamin, L.A. and Solomon, T. and Kneen, R. and Pett, S. and Thomas, R.H. and Michael, B.D. and 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): fcab168. ISSN 2632-1297

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.