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6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records

Maxime Taquet, John R Geddes, Masud Husain and 2 more

The Lancet Psychiatry · 2021 · CC BY

doi:10.1016/s2215-0366(21)00084-5

Abstract

Background. Neurological and psychiatric sequelae of COVID-19 have been reported, but more data are needed to adequately assess the effects of COVID-19 on brain health. We aimed to provide robust estimates of incidence rates and relative risks of neurological and psychiatric diagnoses in patients in the 6 months following a COVID-19 diagnosis.

Methods. For this retrospective cohort study and time-to-event analysis, we used data obtained from the TriNetX electronic health records network (with over 81 million patients). Our primary cohort comprised patients who had a COVID-19 diagnosis; one matched control cohort included patients diagnosed with influenza, and the other matched control cohort included patients diagnosed with any respiratory tract infection including influenza in the same period. Patients with a diagnosis of COVID-19 or a positive test for SARS-CoV-2 were excluded from the control cohorts. All cohorts included patients older than 10 years who had an index event on or after Jan 20, 2020, and who were still alive on Dec 13, 2020. We estimated the incidence of 14 neurological and psychiatric outcomes in the 6 months after a confirmed diagnosis of COVID-19: intracranial haemorrhage; ischaemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root, and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders (grouped and separately); substance use disorder; and insomnia. Using a Cox model, we compared incidences with those in propensity score-matched cohorts of patients with influenza or other respiratory tract infections. We investigated how these estimates were affected by COVID-19 severity, as proxied by hospitalisation, intensive therapy unit (ITU) admission, and encephalopathy (delirium and related disorders). We assessed the robustness of the differences in outcomes between cohorts by repeating the analysis in different scenarios. To provide benchmarking for the incidence and risk of neurological and psychiatric sequelae, we compared our primary cohort with four cohorts of patients diagnosed in the same period with additional index events: skin infection, urolithiasis, fracture of a large bone, and pulmonary embolism.

Findings. Among 236 379 patients diagnosed with COVID-19, the estimated incidence of a neurological or psychiatric diagnosis in the following 6 months was 33·62% (95% CI 33·17–34·07), with 12·84% (12·36–13·33) receiving their first such diagnosis. For patients who had been admitted to an ITU, the estimated incidence of a diagnosis was 46·42% (44·78–48·09) and for a first diagnosis was 25·79% (23·50–28·25). Regarding individual diagnoses of the study outcomes, the whole COVID-19 cohort had estimated incidences of 0·56% (0·50–0·63) for intracranial haemorrhage, 2·10% (1·97–2·23) for ischaemic stroke, 0·11% (0·08–0·14) for parkinsonism, 0·67% (0·59–0·75) for dementia, 17·39% (17·04–17·74) for anxiety disorder, and 1·40% (1·30–1·51) for psychotic disorder, among others. In the group with ITU admission, estimated incidences were 2·66% (2·24–3·16) for intracranial haemorrhage, 6·92% (6·17–7·76) for ischaemic stroke, 0·26% (0·15–0·45) for parkinsonism, 1·74% (1·31–2·30) for dementia, 19·15% (17·90–20·48) for anxiety disorder, and 2·77% (2·31–3·33) for psychotic disorder. Most diagnostic categories were more common in patients who had COVID-19 than in those who had influenza (hazard ratio [HR] 1·44, 95% CI 1·40–1·47, for any diagnosis; 1·78, 1·68–1·89, for any first diagnosis) and those who had other respiratory tract infections (1·16, 1·14–1·17, for any diagnosis; 1·32, 1·27–1·36, for any first diagnosis). As with incidences, HRs were higher in patients who had more severe COVID-19 (eg, those admitted to ITU compared with those who were not: 1·58, 1·50–1·67, for any diagnosis; 2·87, 2·45–3·35, for any first diagnosis). Results were robust to various sensitivity analyses and benchmarking against the four additional index health events.

Interpretation. Our study provides evidence for substantial neurological and psychiatric morbidity in the 6 months after COVID-19 infection. Risks were greatest in, but not limited to, patients who had severe COVID-19. This information could help in service planning and identification of research priorities. Complementary study designs, including prospective cohorts, are needed to corroborate and explain these findings.

Funding. National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre.

References 30

  1. 1.
    Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic · 2020
    No notice
  2. 2.

    Ellul MA, Benjamin L, Singh B. Neurological associations of COVID-19. Lancet Neurol. 2020;19:767-783.

    Not in our library10.1016/s1474-4422(20)30221-0

  3. 3.

    Varatharaj A, Thomas N, Ellul MA. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study. Lancet Psychiatry. 2020;7:875-882.

    Not in our library10.1016/s2215-0366(20)30287-x

  4. 4.
    The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings · 2020
    No notice
  5. 5.

    Kremer S, Lersy F, Anheim M. Neurologic and neuroimaging findings in patients with COVID-19: a retrospective multicenter study. Neurology. 2020;95:e1868-e1882.

    Not in our library10.1212/wnl.0000000000010112

  6. 6.

    Pezzini A, Padovani A. Lifting the mask on neurological manifestations of COVID-19. Nat Rev Neurol. 2020;16:636-644.

    Not in our library10.1038/s41582-020-0398-3

  7. 7.

    Raman B, Cassar MP, Tunnicliffe EM. Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge. EClinicalMedicine. 2021;31.

    Not in our library10.1016/j.eclinm.2020.100683

  8. 8.

    Iadecola C, Anrather J, Kamel H. Effects of COVID-19 on the nervous system. Cell. 2020;183:16-27.

    Not in our library10.1016/j.cell.2020.08.028

  9. 9.

    Kreye J, Reincke SM, Prüss H. Do cross-reactive antibodies cause neuropathology in COVID-19? Nat Rev Immunol. 2020;20:645-646.

    Not in our library10.1038/s41577-020-00458-y

  10. 10.

    Meinhardt J, Radke J, Dittmayer C. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat Neurosci. 2021;24:168-175.

    Not in our library10.1038/s41593-020-00758-5

  11. 11.

    Rhea EM, Logsdon AF, Hansen KM. The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice. Nat Neurosci. 2021;24:368-378.

    Not in our library10.1038/s41593-020-00771-8

  12. 12.

    Holmes EA, O'Connor RC, Perry VH. Multidisciplinary research priorities for the COVID-19 pandemic: a call for action for mental health science. Lancet Psychiatry. 2020;7:547-560.

    Not in our library10.1016/s2215-0366(20)30168-1

  13. 13.

    Vindegaard N, Benros ME. COVID-19 pandemic and mental health consequences: systematic review of the current evidence. Brain Behav Immun. 2020;89:531-542.

    Not in our library10.1016/j.bbi.2020.05.048

  14. 14.
    Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA · 2021
    Corrected
  15. 15.
    Risk factors for SARS-CoV-2 among patients in the Oxford Royal College of General Practitioners Research and Surveillance Centre primary care network: a cross-sectional study · 2020
    No notice
  16. 16.
    Factors associated with COVID-19-related death using OpenSAFELY · 2020
    No notice
  17. 17.

    Slooter AJC, Otte WM, Devlin JW. Updated nomenclature of delirium and acute encephalopathy: statement of ten Societies. Intensive Care Med. 2020;46:1020-1022.

    Not in our library10.1007/s00134-019-05907-4

  18. 18.

    Oldham MA, Slooter AJC, Cunningham C. Characterising neuropsychiatric disorders in patients with COVID-19. Lancet Psychiatry. 2020;7:932-933.

    Not in our library10.1016/s2215-0366(20)30346-1

  19. 19.

    Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res. 2011;46:399-424.

    Not in our library10.1080/00273171.2011.568786

  20. 20.

    Haukoos JS, Lewis RJ. The propensity score. JAMA. 2015;314:1637-1638.

    Not in our library10.1001/jama.2015.13480

  21. 21.

    Royston P, Parmar MKB. Flexible parametric proportional-hazards and proportional-odds models for censored survival data, with application to prognostic modelling and estimation of treatment effects. Stat Med. 2002;21:2175-2197.

    Not in our library10.1002/sim.1203

  22. 22.

    Panigada M, Bottino N, Tagliabue P. Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis. J Thromb Haemost. 2020;18:1738-1742.

    Not in our library10.1111/jth.14850

  23. 23.

    Siow I, Lee KS, Zhang JJY, Saffari SE, Ng A, Young B. Stroke as a neurological complication of COVID-19: a systematic review and meta-analysis of incidence, outcomes and predictors. J Stroke Cerebrovasc Dis. 2021;30.

    Not in our library10.1016/j.jstrokecerebrovasdis.2020.105549

  24. 24.

    Hernandez-Fernandez F, Valencia HS, Barbella-Aponte R. Cerebrovascular disease in patients with COVID-19: neuroimaging, histological and clinical description. Brain. 2020;143:3089-3103.

    Not in our library10.1093/brain/awaa239

  25. 25.

    Xie Y, Bowe B, Maddukuri G, Al-Aly Z. Comparative evaluation of clinical manifestations and risk of death in patients admitted to hospital with COVID-19 and seasonal influenza: cohort study. BMJ. 2020;371.

    Not in our library10.1136/bmj.m4677

  26. 26.

    Keddie S, Pakpoor J, Mousele C. Epidemiological and cohort study finds no association between COVID-19 and Guillain-Barré syndrome. Brain. 2020.

    Not in our library10.1093/brain/awaa433

  27. 27.

    Hoffman LA, Vilensky JA. Encephalitis lethargica: 100 years after the epidemic. Brain. 2017;140:2246-2251.

    Not in our library10.1093/brain/awx177

  28. 28.

    Watson CJ, Thomas RH, Solomon T, Michael BD, Nicholson TR, Pollak TA. COVID-19 and psychosis risk: real or delusional concern? Neurosci Lett. 2021;741.

    Not in our library10.1016/j.neulet.2020.135491

  29. 29.

    Casey JA, Schwartz BS, Stewart WF, Adler NE. Using electronic health records for population health research: a review of methods and applications. Annu Rev Public Health. 2016;37:61-81.

    Not in our library10.1146/annurev-publhealth-032315-021353

  30. 30.
    Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study · 2020
    No notice

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