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

  1. James B. Badenoch
  2. Emma R. Rengasamy
  3. Cameron Watson
  4. Katrin Jansen
  5. Stuti Chakraborty
  6. Ritika D. Sundaram
  7. Danish Hafeez
  8. Ella Burchill
  9. Aman Saini
  10. Lucretia Thomas
  11. Benjamin Cross
  12. Camille K. Hunt
  13. Isabella Conti
  14. Sylvia Ralovska
  15. Zain Hussain
  16. Matthew Butler
  17. Thomas A. Pollak
  18. Ivan Koychev
  19. Benedict D. Michael
  20. Heinz Holling
  21. Timothy R. Nicholson
  22. Jonathan P. Rogers
  23. Alasdair G. Rooney

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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.

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  1. Version published to 10.1093/braincomms/fcab297
  2. ScreenIT

    SciScore for 10.1101/2021.04.30.21256413: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    BlindingScreening and data extraction: Screening of titles, abstracts, and full text was conducted by a minimum of two authors each blinded to the other’s ratings using Rayyan (www.rayyan.ai).
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search strategy: We searched Ovid MEDLINE(R) and Epub Ahead of Print, In-Process and Other Non-Indexed Citations and Daily, EMBASE (via Ovid), APA PsycInfo (via OVID) and CINAHL (via EBSCO) from 1st January 2020 to 20th February 2021.
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)
    We defined objective cognitive dysfunction as revealed by a cognitive assessment screening tool (e.g. MMSE, MoCA, or similar).
    MoCA
    suggested: (MOCA, RRID:SCR_010638)

    Results from OddPub: Thank you for sharing your code.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2021.04.30.21256413v1 on medRxiv