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Systematic review
Neurocognitive and psychiatric outcomes associated with postacute COVID-19 infection without severe medical complication: a meta-analysis
  1. Sarah A B Knapp1,2,
  2. David S Austin1,
  3. Stephen L Aita1,3,
  4. Joshua E Caron1,3,
  5. Tyler Owen4,
  6. Nicholas C Borgogna4,5,
  7. Victor A Del Bene6,
  8. Robert M Roth7,8,
  9. William P Milberg9,10,
  10. Benjamin D Hill11
  1. 1Department of Mental Health, VA Maine Healthcare System, Augusta, Maine, USA
  2. 2Department of Mental Health, White River Junction VA Medical Center, White River Junction, Vermont, USA
  3. 3Department of Psychology, University of Maine System, Orono, Maine, USA
  4. 4Department of Psychological Sciences, Texas Tech University, Lubbock, Texas, USA
  5. 5Department of Psychology, University of Alabama at Birmingham School of Social and Behavioral Sciences, Birmingham, Alabama, USA
  6. 6Department of Neurology, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA
  7. 7Department of Psychiatry, Dartmouth Health, Lebanon, New Hampshire, USA
  8. 8Department of Psychiatry, Dartmouth College Geisel School of Medicine, Hanover, New Hampshire, USA
  9. 9Geriatric Research, Education and Clinical Center (GRECC) and Translational Research Center for TBI and Stress Disorders (TRACTS), Boston VA Medical Center, Boston, Massachusetts, USA
  10. 10Department of Psychiatry, Harvard Medical School, Cambridge, Massachusetts, USA
  11. 11Department of Psychology, University of South Alabama, Mobile, Alabama, USA
  1. Correspondence to Dr Stephen L Aita, Department of Mental Health, VA Maine Healthcare System, Augusta, USA; stephen.aita{at}va.gov

Abstract

Background Cognitive symptoms are often reported by those with a history of COVID-19 infection. No comprehensive meta-analysis of neurocognitive outcomes related to COVID-19 exists despite the influx of studies after the COVID-19 pandemic. This study meta-analysed observational research comparing cross-sectional neurocognitive outcomes in adults with COVID-19 (without severe medical/psychiatric comorbidity) to healthy controls (HCs) or norm-referenced data.

Methods Data were extracted from 54 studies published between January 2020 and June 2023. Hedges’ g was used to index effect sizes, which were pooled using random-effects modelling. Moderating variables were investigated using meta-regression and subgroup analyses.

Results Omnibus meta-analysis of 696 effect sizes extracted across 54 studies (COVID-19 n=6676, HC/norm-reference n=12 986; average time since infection=~6 months) yielded a small but significant effect indicating patients with COVID-19 performed slightly worse than HCs on cognitive measures (g=−0.36; 95% CI=−0.45 to –0.28), with high heterogeneity (Q=242.30, p<0.001, τ=0.26). Significant within-domain effects was yielded by cognitive screener (g=−0.55; 95% CI=−0.75 to –0.36), processing speed (g=−0.44; 95% CI=−0.57 to –0.32), global cognition (g=−0.40; 95% CI=−0.71 to –0.09), simple/complex attention (g=−0.38; 95% CI=−0.46 to –0.29), learning/memory (g=−0.34; 95% CI=−0.46 to –0.22), language (g=−0.34; 95% CI=−0.45 to –0.24) and executive function (g=−0.32; 95% CI=−0.43 to –0.21); but not motor (g=−0.40; 95% CI=−0.89 to 0.10), visuospatial/construction (g=−0.09; 95% CI=−0.23 to 0.05) and orientation (g=−0.02; 95% CI=−0.17 to 0.14). COVID-19 samples with elevated depression, anxiety, fatigue and disease severity yielded larger effects.

Conclusion Mild cognitive deficits are associated with COVID-19 infection, especially as detected by cognitive screeners and processing speed tasks. We failed to observe clinically meaningful cognitive impairments (as measured by standard neuropsychological instruments) in people with COVID-19 without severe medical or psychiatric comorbidities.

Data availability statement

Data are available on reasonable request. Data are available on reasonable request to the corresponding author.

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Data availability statement

Data are available on reasonable request. Data are available on reasonable request to the corresponding author.

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Footnotes

  • X @AitaPhD

  • Contributors Concept and design: SABK, DSA, SLA, JEC and BDH. Acquisition, analysis or interpretation of data: SABK, DSA, SLA.Drafting of the manuscript: SABK, DSA, SLA, JEC. Critical revision of the manuscript for important intellectual content: All authors. Statistical analyses: SLA, TO and NCB. Obtaining funding: N/A. Administrative, technical or material support: TO, NCB and BDH. Supervision: SLA, JEC, NCB, VADB, RMR, WPM and BDH. SLA is responsible for the overall content as guarantor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.