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Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis

Research output: Contribution to journalReviewpeer-review

  • Felicia Ceban
  • Susan Ling
  • Leanna M W Lui
  • Yena Lee
  • Hartej Gill
  • Kayla M Teopiz
  • Nelson B Rodrigues
  • Mehala Subramaniapillai
  • Joshua D Di Vincenzo
  • Bing Cao
  • Kangguang Lin
  • Rodrigo B Mansur
  • Roger C Ho
  • Joshua D Rosenblat
  • Kamilla W Miskowiak
  • Maj Vinberg
  • Vladimir Maletic
  • Roger S McIntyre
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IMPORTANCE: COVID-19 is associated with clinically significant symptoms despite resolution of the acute infection (i.e., post-COVID-19 syndrome). Fatigue and cognitive impairment are amongst the most common and debilitating symptoms of post-COVID-19 syndrome.

OBJECTIVE: To quantify the proportion of individuals experiencing fatigue and cognitive impairment 12 or more weeks following COVID-19 diagnosis, and to characterize the inflammatory correlates and functional consequences of post-COVID-19 syndrome.

DATA SOURCES: Systematic searches were conducted without language restrictions from database inception to June 8, 2021 on PubMed/MEDLINE, The Cochrane Library, PsycInfo, Embase, Web of Science, Google/Google Scholar, and select reference lists.

STUDY SELECTION: Primary research articles which evaluated individuals at least 12 weeks after confirmed COVID-19 diagnosis and specifically reported on fatigue, cognitive impairment, inflammatory parameters, and/or functional outcomes were selected.

DATA EXTRACTION & SYNTHESIS: Two reviewers independently extracted published summary data and assessed methodological quality and risk of bias. A meta-analysis of proportions was conducted to pool Freeman-Tukey double arcsine transformed proportions using the random-effects restricted maximum-likelihood model.

MAIN OUTCOMES & MEASURES: The co-primary outcomes were the proportions of individuals reporting fatigue and cognitive impairment, respectively, 12 or more weeks following COVID-19 infection. The secondary outcomes were inflammatory correlates and functional consequences associated with post-COVID-19 syndrome.

RESULTS: The literature search yielded 10,979 studies, and 81 studies were selected for inclusion. The fatigue meta-analysis comprised 68 studies, the cognitive impairment meta-analysis comprised 43 studies, and 48 studies were included in the narrative synthesis. Meta-analysis revealed that the proportion of individuals experiencing fatigue 12 or more weeks following COVID-19 diagnosis was 0.32 (95% CI, 0.27, 0.37; p < 0.001; n = 25,268; I2 = 99.1%). The proportion of individuals exhibiting cognitive impairment was 0.22 (95% CI, 0.17, 0.28; p < 0.001; n = 13,232; I2 = 98.0). Moreover, narrative synthesis revealed elevations in proinflammatory markers and considerable functional impairment in a subset of individuals.

CONCLUSIONS & RELEVANCE: A significant proportion of individuals experience persistent fatigue and/or cognitive impairment following resolution of acute COVID-19. The frequency and debilitating nature of the foregoing symptoms provides the impetus to characterize the underlying neurobiological substrates and how to best treat these phenomena.

STUDY REGISTRATION: PROSPERO (CRD42021256965).

Original languageEnglish
JournalBrain, Behavior, and Immunity
Volume101
Pages (from-to)93-135
Number of pages43
ISSN0889-1591
DOIs
Publication statusPublished - Mar 2022

Bibliographical note

Copyright © 2022 Elsevier Inc. All rights reserved.

    Research areas

  • COVID-19 Testing, COVID-19/complications, Cognitive Dysfunction, Fatigue/etiology, Humans, SARS-CoV-2

ID: 78496823