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Cited by 1,554Long-Term Effects of COVID-19COVID-19 Clinical Research StudiesCOVID-19 and Mental Health

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

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Ceban, Felicia, Ling, Susan, Lui, Leanna M.W., Lee, Yena, Gill, Hartej, Teopiz, Kayla M., Rodrigues, Nelson B., Subramaniapillai, Mehala +10 more·2022·Brain, Behavior, and Immunity
DOI 10.1016/j.bbi.2021.12.020PMC PMC8715665
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Abstract

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; I 2 = 99.1%). The proportion of individuals exhibiting cognitive impairment was 0.22 (95% CI, 0.17, 0.28; p < 0.001; n = 13,232; I 2 = 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).

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  • Cognitive fatigue stands out due to its widespread occurrence and its significant effects on patients' quality of life.

    “Among these symptoms, cognitive fatigue stands out due to its widespread occurrence and its significant effects on patients' quality of life [2].”

    From Evaluating the efficacy of repetitive anodal transcranial direct current stimulation on cognitive fatigue in long COVID: A randomized controlled trial (2025) · cites this paper as [2]

    The Discussion reports that persistent fatigue affects approximately a third of people after COVID-19 and cognitive impairment over a fifth, and associates these symptoms with marked functional impairment (page unavailable). The Results’ Functional Outcomes/Quality of Life section reports links to activity difficulties and lower quality-of-life scores, but the paper assesses fatigue and cognitive impairment separately; it does not establish the prevalence or quality-of-life effects of a distinct symptom called “cognitive fatigue.” (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Ceban, F., Ling, S., Lui, L. M. W., Lee, Y., Gill, H., Teopiz, K. M., Rodrigues, N. B., Subramaniapillai, M., Di Vincenzo, J. D., Cao, B., Lin, K., Mansur, R. B., Ho, R. C., Rosenblat, J. D., Miskowiak, K. W., Vinberg, M., Maletic, V., & McIntyre, R. S.
Affiliations
  • University Health Network (CA)
  • Southwest University (CN)
  • Guangzhou Medical University (CN)
  • National University of Singapore (SG)
  • University of Copenhagen (DK)
  • University of South Carolina (US)
Corresponding author
McIntyre, Roger S.
ORCID
Venue
Brain, Behavior, and Immunity
Publisher
Elsevier BV
Published
2022-03
Volume
101
Pages
93-135
ISSN
0889-1591 (ISSN-L)
DOI
10.1016/j.bbi.2021.12.020
PMC
PMC8715665
OpenAlex
W4200066487
Cited by
1,554
References
14
Citations by year
2026: 139 · 2025: 312 · 2024: 428 · 2023: 469 · 2022: 204 · 2013: 1
FWCI
35.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Behavior and Immunity (publishedVersion)
  • PubMed Central (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Topics
  • Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Social Sciences › Psychology › Clinical Psychology › COVID-19 and Mental Health
Keywords
long COVID, fatigue, cognitive impairment, pro-inflammatory markers, inflammation, functional disability
MeSH terms
COVID-19, SARS-CoV-2, COVID-19 Testing, Post-Acute COVID-19 Syndrome, Fatigue, Humans, Cognitive Dysfunction

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