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Neuropsychiatry
Review
Neurology and neuropsychiatry of COVID-19: a systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives
  1. Jonathan P Rogers1,2,
  2. Cameron J Watson3,
  3. James Badenoch4,
  4. Benjamin Cross5,
  5. Matthew Butler6,
  6. Jia Song7,
  7. Danish Hafeez8,
  8. Hamilton Morrin9,
  9. Emma Rachel Rengasamy10,
  10. Lucretia Thomas11,
  11. Silviya Ralovska12,
  12. Abigail Smakowski2,
  13. Ritika Dilip Sundaram13,
  14. Camille Kaitlyn Hunt14,
  15. Mao Fong Lim15,
  16. Daruj Aniwattanapong6,16,
  17. Vanshika Singh17,
  18. Zain Hussain18,
  19. Stuti Chakraborty19,
  20. Ella Burchill20,
  21. Katrin Jansen21,
  22. Heinz Holling21,
  23. Dean Walton22,
  24. Thomas A Pollak6,
  25. Mark Ellul22,23,24,
  26. Ivan Koychev25,26,
  27. Tom Solomon22,23,
  28. Benedict Daniel Michael22,23,24,
  29. Timothy R Nicholson6,
  30. Alasdair G Rooney27
  1. 1 Division of Psychiatry, University College London, London, UK
  2. 2 South London and Maudsley NHS Foundation Trust, London, UK
  3. 3 Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK
  4. 4 Medical School, University of Birmingham, Birmingham, UK
  5. 5 East Lancashire Hospitals NHS Trust, Blackburn, UK
  6. 6 Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
  7. 7 East London NHS Foundation Trust, London, UK
  8. 8 School of Medical Sciences, The University of Manchester, Manchester, UK
  9. 9 Maidstone & Tunbridge Wells NHS Trust, Maidstone, UK
  10. 10 Cwm Taf Morgannwg University Health Board, Abercynon, UK
  11. 11 College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
  12. 12 Department of Neurology, Psychiatry, Physiotherapy and Rehabilitation, Preventive Medicine, and Public Health, Sofia University St Kliment Ohridski, Sofia, Bulgaria
  13. 13 School of Medicine, University of Glasgow, Glasgow, UK
  14. 14 Division of Neurology, University of British Columbia, Vancouver, B.C, Canada
  15. 15 Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  16. 16 Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
  17. 17 The Wire, New Delhi, India
  18. 18 College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, UK
  19. 19 Department of Physical Medicine and Rehabilitation, Christian Medical College Vellore, Vellore, Tamil Nadu, India
  20. 20 Faculty of Medicine and Life Sciences, King's College London, London, UK
  21. 21 Department of Psychology, University of Münster, Münster, Germany
  22. 22 Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, UK
  23. 23 National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infection, University of Liverpool, Liverpool, UK
  24. 24 Institute of Infection, Veterinary, and Zoological Science, University of Liverpool, Liverpool, UK
  25. 25 Department of Psychiatry, University of Oxford, Oxford, UK
  26. 26 Department of Psychological Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
  27. 27 Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK
  1. Correspondence to Dr Jonathan P Rogers, Division of Psychiatry, University College London, London W1T 7NF, UK; jonathan.rogers{at}ucl.ac.uk

Abstract

There is accumulating evidence of the neurological and neuropsychiatric features of infection with SARS-CoV-2. In this systematic review and meta-analysis, we aimed to describe the characteristics of the early literature and estimate point prevalences for neurological and neuropsychiatric manifestations.

We searched MEDLINE, Embase, PsycINFO and CINAHL up to 18 July 2020 for randomised controlled trials, cohort studies, case-control studies, cross-sectional studies and case series. Studies reporting prevalences of neurological or neuropsychiatric symptoms were synthesised into meta-analyses to estimate pooled prevalence.

13 292 records were screened by at least two authors to identify 215 included studies, of which there were 37 cohort studies, 15 case-control studies, 80 cross-sectional studies and 83 case series from 30 countries. 147 studies were included in the meta-analysis. The symptoms with the highest prevalence were anosmia (43.1% (95% CI 35.2% to 51.3%), n=15 975, 63 studies), weakness (40.0% (95% CI 27.9% to 53.5%), n=221, 3 studies), fatigue (37.8% (95% CI 31.6% to 44.4%), n=21 101, 67 studies), dysgeusia (37.2% (95% CI 29.8% to 45.3%), n=13 686, 52 studies), myalgia (25.1% (95% CI 19.8% to 31.3%), n=66 268, 76 studies), depression (23.0% (95% CI 11.8% to 40.2%), n=43 128, 10 studies), headache (20.7% (95% CI 16.1% to 26.1%), n=64 613, 84 studies), anxiety (15.9% (5.6% to 37.7%), n=42 566, 9 studies) and altered mental status (8.2% (95% CI 4.4% to 14.8%), n=49 326, 19 studies). Heterogeneity for most clinical manifestations was high.

Neurological and neuropsychiatric symptoms of COVID-19 in the pandemic’s early phase are varied and common. The neurological and psychiatric academic communities should develop systems to facilitate high-quality methodologies, including more rapid examination of the longitudinal course of neuropsychiatric complications of newly emerging diseases and their relationship to neuroimaging and inflammatory biomarkers.

  • psychiatry
  • clinical neurology
  • systematic reviews
  • COVID-19
  • meta-analysis

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

https://bmj.com/coronavirus/usage

https://doi.org/10.1136/jnnp-2021-326405

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    Footnotes

    • JPR and CJW are joint first authors.

    • TRN and AGR are joint senior authors.

    • Twitter @drjprogers, @Camer0nWatson, @BadenochJamie, @BenCross23, @mattbutlerpsych, @jiasongpsych, @danish_hafeez1, @Hammy_UK, @emmarachelsamy, @lucretiaathomas, @ralovska, @abismakowski, @maotweets, @EarlNeuroPsy, @vanshika_writes, @ella_burchill, @tompollak, @Melibeus, @IvanKoychev, @RunningMadProf, @BenedictNeuro, @Tim_R_Nicholson, @allyrooney

    • Contributors TRN and AR conceived the study. AR and JPR led and coordinated the study. MB compared the work with other systematic reviews. CW, BC, MB, JS, DH, ERR, LT, AR, MFL and JB screened studies for eligibility. AR, JPR, JS and MB consulted on study inclusion. CW, BC, DH, HM, ERR, LT, SR, RDS and JB extracted the data. JB, MB, JS, DH, HM, ERR, LT, SR, AS, RDS, CKH, MFL, DA, AR and BC checked data extraction. AR conducted OCEBM ratings. JPR calculated descriptive statistics. CW and KJ conducted the meta-analysis, supported by HH. CW and DH created figures. JPR, BC, MB, JS, DH, HM, LT, SR, AS, RDS, CKH, MFL, VS, ZH, SC, EB, DW, TAP, ME, IK, TRN, AR and JB conducted quality assessment. JPR and AS supervised and arbitrated quality assessment. JB made the PRISMA flow chart. JPR, MB and JB sorted references. JB checked adherence to PRISMA guidelines. AR, JPR, JB, ERR, VS and MB drafted the manuscript. JPR, MB, JS and JB checked the completed manuscript. ERR and ZH created tables. MFL sorted funding statements. JPR and EB formatted the manuscript. DW, ME, IK, TS, BDM, TRN, AR and TAP provided senior review of the manuscript. JPR and AR are responsible for the overall content of the study.

    • Funding JPR is supported by a Wellcome Trust Clinical Training Fellowship (102186/B/13/Z). MB is a National Institute of Health Research (NIHR) Academic Clinical Fellow (ACF-2019-17-008). HH is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) (HO1286/16-1). TAP is supported by an NIHR Clinical Lectureship (no award/grant number). ME is supported by the Association of British Neurologists through a Clinical Research Training Fellowship (no award/grant number). ME and TS are supported by the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England, in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (NIHR200907). IK is supported by the Medical Research Council (Dementias Platform UK Grant MR/L023784/2) and the Oxford Health Biomedical Research Centre (no award/grant number). DA is supported by the Faculty of Medicine, Chulalongkorn University, Thailand (no award/grant number). AR is supported by the Royal College of Physicians of Edinburgh, John, Margaret, Alfred and Stewart Sim Fellowship 2018–2020 (no award/grant number). BDM is supported by the UKRI/MRC COVID-CNS grant (MR/V03605X/1), the MRC-CSF (MR/V007181/1), and the MRC/AMED grant (MR/T028750/1).

    • Disclaimer The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

    • Map disclaimer The depiction of boundaries on the map(s) in this article does not imply the expression of any opinion whatsoever on the part of BMJ (or any member of its group) concerning the legal status of any country, territory, jurisdiction or area or of its authorities. The map(s) are provided without any warranty of any kind, either express or implied.

    • Competing interests JPR has received payment from the Alberta Psychiatric Association for a lecture and has held one unpaid advisory meeting with representatives from Promentis Pharmaceuticals regarding drug development. LT is in receipt of a bursary as part of the Royal College of Psychiatrists PsychStar scheme. By winning a prize from the Royal College of Psychiatrists, she has received prize money and free attendance at a meeting. She is President of the University of Birmingham Psychiatry Society. IK has been supported by the Medical Research Council through Dementias Platform UK and by the National Institute for Health Research (NIHR) through the Oxford Health Biomedical Research Centre. He has been a medical advisor to Mantrah and Sharp Therapeutics, digital technology start-ups. He holds stock options in Sharp Therapeutics. TS is supported by the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections (grant nos. IS-HPU-1112-10117 and NIHR200907), NIHR Programme Grant for Applied Research (no. RP-PG-0108-10,048), NIHR Global Health Research Group on Brain Infections (no. 17/63/110), and the European Union’s Horizon 2020 research and innovation programme ZikaPLAN (Preparedness Latin America Network), grant agreement no. 734584. He receives royalties from Oxford University Press, Elsevier, Liverpool University Press and Cambridge University Press. He is a consultant for the MHRA Vaccine Benefit Risk Expert Working Group. He filed for a patent on a test for bacterial meningitis based on a blood test (no. GB1606537.7 14 April 2016). He was on the Data Safety Monitoring Committee of the GSK Study to Evaluate the Safety and Immunogenicity of a Candidate Ebola Vaccine in Children GSK3390107A (ChAd3 EBO-Z) vaccine. He chaired the Siemens Healthineers Clinical Advisory Board (1) Data Safety Monitoring Board: Study of Ebola vaccine ChAd3-EBO-Z-Commercial entity. He holds shares in Medefer Solutions. BDM has received payment for a lecture for Valneva.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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