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.
Highlights
COVID-19 causes a multi-system disorder associated with a broad spectrum of neurological and neuropsychiatric complications[1, 2]
10-25% of patients hospitalised with COVID-19 present with or develop a significant neurological disorder[4,5,6,7,8], the risk of which may increase with disease severity[1, 9]
The median (IQR) Rockwood frailty score before COVID-19 was 3 (2-5)
Summary
COVID-19 causes a multi-system disorder associated with a broad spectrum of neurological and neuropsychiatric complications[1, 2]. As neurological complications are varied and occur throughout the disease course, multiple mechanisms have been proposed These may include direct viral infection of endothelium via angiotensin converting enzyme-2 receptors, systemic inflammation resulting in coagulopathy, cytokine toxicity, blood brain barrier disruption, antibody and cell-mediated autoimmunity and consequences of prolonged severe illness[2, 12,13,14,15]. These suggested pathological processes may co-exist, act synergistically and occur simultaneously in different parts of the nervous system, causing overlapping clinical presentations
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