Evidence map›Paper›PMID 34973396›Full record

SynthesisBrain, behavior, and immunity2022

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

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 and 8 more

5 registry-linked trialsAbstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Brain, behavior, and immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 5 registered trials, which are not on this map. Cited by 821 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
821citing papers in PubMed, 4 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05047952 phase2completednot on this map

Randomized, Double-Blinded, Placebo-Controlled Study Evaluating Vortioxetine for Cognitive Deficits in Persons With Post-COVID-19 Condition

TypeinterventionalSponsorBrain and Cognition Discovery FoundationRan2021 to 2023Enrolled149ConditionsPost-COVID-19 Condition, Post-COVID-19 Syndrome, Cognitive ImpairmentArmsVortioxetine, Placebo
NCT05823896 phase2completednot on this mapstarted 2023, after this paper: background citation

An Interventional, Double-Blinded, 2-Arm Study to Investigate the Efficacy of Orally Administered Nirmatrelvir/Ritonavir Compared with Placebo/Ritonavir in Non-hospitalized Adult Participants Suffering from Post-COVID

TypeinterventionalSponsorKarolinska InstitutetRan2023 to 2024Enrolled219ConditionsPost-COVID-19 Syndrome, Long COVID, Long Covid19, COVID-19ArmsNirmatrelvir/ritonavir, Placebo/ritonavir
NCT05874089 naunknown statusnot on this map

The Role of VSL#3® in the Treatment of Fatigue and Other Symptoms in Long Covid-19 Syndrome: a Randomized, Double-blind, Placebo-controlled Study (DELong#3)

TypeinterventionalSponsorFondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoRan2022 to 2023Enrolled96ConditionsLong COVIDArmsVSL#3®, Placebo
NCT05986422 phase2terminatednot on this mapstarted 2023, after this paper: background citation

Phase 2a, Double-blind, Randomized, Placebo-controlled Trial of Methylprednisolone Versus Placebo in Patients With Cognitive Deficits in Post-COVID-19 Syndrome (PCS)

TypeinterventionalSponsorCharite University, Berlin, GermanyRan2023 to 2026Enrolled96ConditionsPost-COVID-19 SyndromeArmsMethylprednisolone
NCT06042530 unknown statusnot on this map

Cognitive Impairment and Fatigue After Mild to Moderate COVID-19 - Relation to Biomarkers and Neuronal Network Functions

TypeobservationalSponsorDanderyd HospitalRan2021 to 2025Enrolled100ConditionsPost COVID-19 Condition, Cognitive Impairment, Fatigue, MentalArmsNeuropsychological investigation, Optometric investigation, Magnetic Resonance Imaging, Immunological biomarkers
3 · Its place in the literature

Who cites it

821 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Predictors of Anxiety, Depression, and Stress in Long COVID: Systematic Review of Prevalence.International journal of environmental research and public health · 2025
    Pooled it
  4. Pooled it
  5. Trial
  6. Trial
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  8. Article
  9. Human brain matters: Navigating the neuropathology of COVID-19.Brain pathology (Zurich, Switzerland) · 2026
    Review
  10. Article
  11. Article
  12. Article
  13. Observational
  14. Review
  15. Article
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  20. Article

761 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Felicia CebanMood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada.
Susan LingMood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada.
Leanna M W LuiMood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
Yena LeeMood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Braxia Health, Mississauga, ON, Canada.
Hartej GillMood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
Kayla M TeopizMood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
Nelson B RodriguesMood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
Mehala SubramaniapillaiMood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
Joshua D Di VincenzoMood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada.
Bing CaoKey Laboratory of Cognition and Personality, Faculty of Psychology, Ministry of Education, Southwest University, Chongqing 400715, China.
Kangguang LinDepartment of Affective Disorders, The Affiliated Brain Hospital of Guangzhou Medical University, (Guangzhou Huiai Hospital), Guangzhou Medical University, Guangzhou, China; Laboratory of Emotion and Cognition, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou Medical University, Guangzhou, China.
Rodrigo B MansurMood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Roger C HoDepartment of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore.
Joshua D RosenblatMood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Kamilla W MiskowiakDepartment of Psychology, University of Copenhagen, Copenhagen, Denmark; Mental Health Services, Capital Region of Denmark, Copenhagen University Hospital, Copenhagen, Denmark.
Maj VinbergFaculty of Health and Medical Sciences, University of Copenhagen, Denmark; Psychiatric Research Unit, Psychiatric Centre North Zealand, Hillerød, Denmark.
Vladimir MaleticDepartment of Psychiatry, University of South Carolina, Greenville, SC, USA.
Roger S McIntyreMood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Braxia Health, Mississauga, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address: Roger.McIntyre@uhn.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

importanceCOVID-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.

objectiveTo 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.

resultsThe 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 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).

Indexed as

Cognitive DysfunctionCOVID-19COVID-19 TestingFatigueHumansPost-Acute COVID-19 SyndromeSARS-CoV-2AnhedoniaBipolarBrainBrain fogCognitionCognitive impairmentCOVID-19DepressionFatigueFunctional outcomesImmunologyInflammationLong COVIDMental illnessPopulation healthPost-COVID-19 conditionPost-COVID-19 syndrome

Identifiers

PMID34973396
PMCPMC8715665

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.