Persistent neuropsychiatric symptoms after COVID-19: a systematic review and meta-analysis

Author:

Badenoch James B.12ORCID,Rengasamy Emma R.3,Watson Cameron14,Jansen Katrin5,Chakraborty Stuti67,Sundaram Ritika D.8,Hafeez Danish9ORCID,Burchill Ella10ORCID,Saini Aman11,Thomas Lucretia12,Cross Benjamin13,Hunt Camille K.14,Conti Isabella15,Ralovska Sylvia16,Hussain Zain1718,Butler Matthew19,Pollak Thomas A.20ORCID,Koychev Ivan2122,Michael Benedict D.232425,Holling Heinz5,Nicholson Timothy R.26,Rogers Jonathan P.2728ORCID,Rooney Alasdair G.29

Affiliation:

1. Barts Health NHS Trust, London, UK

2. Queen Mary University of London, London, UK

3. Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

4. Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK

5. Department of Psychology, University of Münster, Münster, Germany

6. Department of Physical Medicine and Rehabilitation, Christian Medical College and Hospital, Vellore, India

7. Occupational Therapy Unit, Department of Physical Medicine and Rehabilitation, Christian Medical College and Hospital, Vellore, India

8. School of Medicine, University of Glasgow, Glasgow, UK

9. Homerton University Hospitals Foundation Trust, London, UK

10. Faculty of Medicine and Life Sciences, King’s College London, London, UK

11. Medical School, University College London, London, UK

12. College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

13. East Lancashire Hospitals NHS Trust, Lancashire, UK

14. Warwick Medical School, Coventry, UK

15. School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK

16. Sofia University ‘St Kliment Ohridski’, bul, ‘Tsar Osvoboditel’ 15, Sofia, Bulgaria

17. Edinburgh Medical School, College of Medicine and Veterinary Medicine, University of Edinburgh, UK

18. School of Medicine, University of Dundee, Dundee, UK

19. Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

20. Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

21. Department of Psychiatry, University of Oxford, Oxford, UK

22. Department of Psychological Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK

23. Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, UK

24. National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infection, University of Liverpool, Liverpool, UK

25. Clinical Infection Microbiology and Immunology, Institute of Infection, Veterinary, and Zoological Science, University of Liverpool, Liverpool, UK

26. Section of Cognitive Neuropsychiatry, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

27. Division of Psychiatry, University College London, London, UK

28. South London and Maudsley NHS Foundation Trust, London, UK

29. Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK

Abstract

Abstract The nature and extent of persistent neuropsychiatric symptoms after COVID-19 are not established. To help inform mental health service planning in the pandemic recovery phase, we systematically determined the prevalence of neuropsychiatric symptoms in survivors of COVID-19. For this pre-registered systematic review and meta-analysis (PROSPERO ID CRD42021239750), we searched MEDLINE, EMBASE, CINAHL and PsycINFO to 20 February 2021, plus our own curated database. We included peer-reviewed studies reporting neuropsychiatric symptoms at post-acute or later time-points after COVID-19 infection and in control groups where available. For each study, a minimum of two authors extracted summary data. For each symptom, we calculated a pooled prevalence using generalized linear mixed models. Heterogeneity was measured with I2. Subgroup analyses were conducted for COVID-19 hospitalization, severity and duration of follow-up. From 2844 unique titles, we included 51 studies (n = 18 917 patients). The mean duration of follow-up after COVID-19 was 77 days (range 14–182 days). Study quality was most commonly moderate. The most prevalent neuropsychiatric symptom was sleep disturbance [pooled prevalence = 27.4% (95% confidence interval 21.4–34.4%)], followed by fatigue [24.4% (17.5–32.9%)], objective cognitive impairment [20.2% (10.3–35.7%)], anxiety [19.1% (13.3–26.8%)] and post-traumatic stress [15.7% (9.9–24.1%)]. Only two studies reported symptoms in control groups, both reporting higher frequencies in COVID-19 survivors versus controls. Between-study heterogeneity was high (I2 = 79.6–98.6%). There was little or no evidence of differential symptom prevalence based on hospitalization status, severity or follow-up duration. Neuropsychiatric symptoms are common and persistent after recovery from COVID-19. The literature on longer-term consequences is still maturing but indicates a particularly high prevalence of insomnia, fatigue, cognitive impairment and anxiety disorders in the first 6 months after infection.

Funder

Medical Research Council/UK Research and Innovation

Wellcome Trust

National Institute for Health Research

Medical Research Council

German Research Foundation

Publisher

Oxford University Press (OUP)

Subject

General Earth and Planetary Sciences,General Environmental Science

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