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

Author:

Ross Russell Amy L12,Hardwick Marc23ORCID,Jeyanantham Athavan3,White Laura M4,Deb Saumitro5,Burnside Girvan6,Joy Harriet M7,Smith Craig J89,Pollak Thomas A10,Nicholson Timothy R10,Davies Nicholas W S11,Manji Hadi1213,Easton Ava1415,Ray Stephen1516,Zandi Michael S13ORCID,Coles Jonathan P17ORCID,Menon David K17,Varatharaj Aravinthan23,McCausland Beth2318,Ellul Mark A151619,Thomas Naomi2021,Breen Gerome22,Keddie Stephen2324ORCID,Lunn Michael P1213ORCID,Burn John P S25,Quattrocchi Graziella26,Dixon Luke27,Rice Claire M2829,Pengas George2,Al-Shahi Salman Rustam30,Carson Alan30,Joyce Eileen M13,Turner Martin R31ORCID,Benjamin Laura A151632,Solomon Tom151619,Kneen Rachel1533,Pett Sarah3435,Thomas Rhys H202136,Michael Benedict D151619,Galea Ian23ORCID

Affiliation:

1. NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK

2. Department of Neurology, Wessex Neurological Centre, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK

3. Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK

4. Liverpool University Hospitals NHS Foundation Trust, Liverpool, L9 7AL, UK

5. Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, L3 5TR, UK

6. Department of Health Data Science, University of Liverpool, Liverpool, L69 3BX, UK

7. Neuroradiology Department, Wessex Neurological Centre, University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, UK

8. Manchester Centre for Clinical Neurosciences, Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Salford Royal Foundation Trust, Salford, M6 8HD, UK

9. Division of Cardiovascular Sciences, Lydia Becker Institute for Immunology and Inflammation, University of Manchester, Manchester, M13 9PL, UK

10. Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, SE5 8AF, UK

11. Chelsea and Westminster NHS Foundation Trust, London, London, SW10 9NH, UK

12. MRC Centre for Neuromuscular Diseases, National Hospital for Neurology, London, WC1N 3BG, UK

13. UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK

14. Encephalitis Society, Malton, Malton, YO17 7DT, UK

15. Department of Clinical Infection Microbiology and Immunology, Institute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool, L7 3EA, UK

16. The National Institute for Health Research Health Protection Research Unit for Emerging and Zoonotic Infections, University of Liverpool, Liverpool, L69 7BE, UK

17. Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, CB2 0SP, UK

18. Memory Assessment and Research Centre, Moorgreen Hospital, Southern Health Foundation Trust, Southampton, SO40 2RZ, UK

19. Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, L9 7LJ, UK

20. Translational and Clinical Research Institute, Newcastle University, Newcastle, NE1 7RU, UK

21. Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle, NE2 4HH, UK

22. Department of Social Genetic and Developmental Psychiatry, King’s College London, London, SE5 8AF, UK

23. Department of Neuromuscular Diseases, University College London, London, WC1N 3BG, UK

24. National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, WC1N 3BG, UK

25. Rehabilitation Department, Poole Hospital, University Hospitals Dorset NHS Foundation Trust, Poole, BH15 2JB, UK

26. Department of Neurology, North Middlesex University Hospital NHS Trust, London, N18 1QX, UK

27. Department of Neuroradiology, Imperial College NHS Healthcare Trust, London, W2 1NY, UK

28. Department of Neurology, Southmead Hospital, North Bristol NHS Trust, Bristol, S10 5NB, UK

29. Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 1TH, UK

30. Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, EH16 4SB, UK

31. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK

32. Laboratory of Molecular and Cell Biology, UCL, Gower St, King’s Cross, London, London, WC1E 6BT, UK

33. Department of Neurology, Alder Hey Children’s NHS Foundation Trust, Liverpool, Liverpool, L14 5AB, UK

34. Medical Research Council Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, WC1V 6LJ, UK

35. Institute for Global Health, University College London, London, WC1N 1EH, UK

36. Department of Neurology, Royal Victoria Infirmary, Newcastle, NE1 4LP, UK

Abstract

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.

Funder

National Institute for Health Research and Medical Research Council

NIHR Cambridge Biomedical Research Centre

Medical Research Council

Wellcome

National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections at University of Liverpool

National Institute for Health Research Global Health Research Group on Brain Infections

European Union's Horizon 2020 research and innovation program ZikaPLAN

Medical Research Council core funding

Publisher

Oxford University Press (OUP)

Subject

General Earth and Planetary Sciences,General Environmental Science

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