Spectrum, risk factors and outcomes of neurological and psychiatric complications of COVID-19: a UK-wide cross-sectional surveillance study
Authors: Ross Russell Amy L , Hardwick Marc , Jeyanantham Athavan , White Laura M , Deb Saumitro , Burnside Girvan , Joy Harriet M , Smith Craig J , Pollak Thomas A , Nicholson Timothy R , Davies Nicholas W S , 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 P S , 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 , Galea Ian 
Published: July 2021

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 &lt;60 years. Relative to those &gt;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.