Display options
Cite
Ceban F, Ling S, Lui LMW, et al. Fatigue and Cognitive Impairment in Post-COVID-19 Syndrome: A Systematic Review and Meta-Analysis. Brain Behav Immun. 2021;doi: 10.1016/j.bbi.2021.12.020.
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. (2021). Fatigue and Cognitive Impairment in Post-COVID-19 Syndrome: A Systematic Review and Meta-Analysis. Brain, behavior, and immunity, . https://doi.org/10.1016/j.bbi.2021.12.020
Ceban, Felicia, et al. "Fatigue and Cognitive Impairment in Post-COVID-19 Syndrome: A Systematic Review and Meta-Analysis." Brain, behavior, and immunity vol. (2021). doi: https://doi.org/10.1016/j.bbi.2021.12.020
Ceban F, Ling S, Lui LMW, Lee Y, Gill H, Teopiz KM, Rodrigues NB, Subramaniapillai M, Di Vincenzo JD, Cao B, Lin K, Mansur RB, Ho RC, Rosenblat JD, Miskowiak KW, Vinberg M, Maletic V, McIntyre RS. Fatigue and Cognitive Impairment in Post-COVID-19 Syndrome: A Systematic Review and Meta-Analysis. Brain Behav Immun. 2021 Dec 29; doi: 10.1016/j.bbi.2021.12.020. Epub 2021 Dec 29. PMID: 34973396; PMCID: PMC8715665.
Copy Download .nbib Format: NLM
Share it on

Brain Behav Immun. 2021 Dec 29; doi: 10.1016/j.bbi.2021.12.020. Epub 2021 Dec 29.

Fatigue and Cognitive Impairment in Post-COVID-19 Syndrome: A Systematic Review and Meta-Analysis.

Brain, behavior, and immunity

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

Affiliations

  1. Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Braxia Health, Mississauga, ON, Canada. Electronic address: [email protected].
  2. Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada. Electronic address: [email protected].
  3. Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada. Electronic address: [email protected].
  4. Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Braxia Health, Mississauga, ON, Canada. Electronic address: [email protected].
  5. Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada. Electronic address: [email protected].
  6. Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada. Electronic address: [email protected].
  7. Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Braxia Health, Mississauga, ON, Canada. Electronic address: [email protected].
  8. Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Braxia Health, Mississauga, ON, Canada. Electronic address: [email protected].
  9. Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada. Electronic address: [email protected].
  10. Key Laboratory of Cognition and Personality, Faculty of Psychology, Ministry of Education, Southwest University, Chongqing, 400715, P. R. China. Electronic address: [email protected].
  11. Department 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. Electronic address: [email protected].
  12. Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address: [email protected].
  13. Department 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. Electronic address: [email protected].
  14. Mood Disorders Psychopharmacology Unit, University Health Network, 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: [email protected].
  15. Department of Psychology, University of Copenhagen, Copenhagen, Denmark; Mental Health services, Capital Region of Denmark, Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: [email protected].
  16. Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Psychiatric Research Unit, Psychiatric Centre North Zealand, Hillerød, Denmark. Electronic address: [email protected].
  17. Department of Psychiatry, University of South Carolina, Greenville, SC, USA. Electronic address: [email protected].
  18. Mood 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: [email protected].

PMID: 34973396 PMCID: PMC8715665 DOI: 10.1016/j.bbi.2021.12.020

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-Turkey 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 after COVID-19 infection. The secondary outcomes were inflammatory correlates and functional consequences of 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

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).

Copyright © 2021. Published by Elsevier Inc.

Keywords: Long COVID; brain fog; cognitive impairment; fatigue; functional outcomes; inflammation; population health; post-COVID-19 condition; post-COVID-19 syndrome

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this pa

References

  1. J Neurosci Nurs. 2012 Aug;44(4):206-17 - PubMed
  2. Lancet Psychiatry. 2021 May;8(5):416-427 - PubMed
  3. Healthcare (Basel). 2021 May 13;9(5): - PubMed
  4. Brain Sci. 2021 Jun 08;11(6): - PubMed
  5. JAMA. 2021 Apr 20;325(15):1525-1534 - PubMed
  6. Depress Anxiety. 2013 Jun;30(6):515-27 - PubMed
  7. World Psychiatry. 2009 Jun;8(2):82-5 - PubMed
  8. Biometrics. 1997 Sep;53(3):983-97 - PubMed
  9. Thorax. 2021 Apr;76(4):399-401 - PubMed
  10. J Intern Med. 2021 Aug;290(2):444-450 - PubMed
  11. Lancet Child Adolesc Health. 2021 Jun;5(6):e22-e23 - PubMed
  12. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jan 3;80(Pt C):291-294 - PubMed
  13. J Affect Disord. 2020 Dec 1;277:55-64 - PubMed
  14. Arch Intern Med. 2009 Dec 14;169(22):2142-7 - PubMed
  15. Br J Anaesth. 2021 Mar;126(3):e110-e113 - PubMed
  16. Respir Med. 2021 Aug;184:106453 - PubMed
  17. J Neurol. 2021 Dec;268(12):4422-4428 - PubMed
  18. Lung. 2021 Apr;199(2):113-119 - PubMed
  19. Evid Based Ment Health. 2019 Nov;22(4):153-160 - PubMed
  20. Brain. 2017 Aug 1;140(8):2246-2251 - PubMed
  21. Eur J Epidemiol. 2010 Sep;25(9):603-5 - PubMed
  22. J Otolaryngol Head Neck Surg. 2020 May 4;49(1):26 - PubMed
  23. Brain Behav Immun. 2021 May;94:138-147 - PubMed
  24. Bipolar Disord. 2017 Dec;19(8):614-626 - PubMed
  25. Int J Environ Res Public Health. 2021 Feb 19;18(4): - PubMed
  26. Lancet. 2021 Jan 16;397(10270):220-232 - PubMed
  27. Eur Heart J. 2020 Sep 1;41(32):3038-3044 - PubMed
  28. JAMA. 2020 Nov 24;324(20):2031-2032 - PubMed
  29. Med (N Y). 2021 Jun 11;2(6):720-735.e4 - PubMed
  30. EClinicalMedicine. 2020 Aug;25:100463 - PubMed
  31. J Infect. 2009 May;58(5):321-8 - PubMed
  32. Brain Sci. 2021 Feb 13;11(2): - PubMed
  33. J Gen Intern Med. 2021 Aug;36(8):2525-2527 - PubMed
  34. J Neurol Sci. 2021 Jul 15;426:117486 - PubMed
  35. Nature. 2020 Sep;585(7825):339-341 - PubMed
  36. Infect Dis (Lond). 2021 Oct;53(10):737-754 - PubMed
  37. BMC Geriatr. 2021 Mar 22;21(1):199 - PubMed
  38. J Psychiatr Res. 2021 Dec;144:129-137 - PubMed
  39. Lancet Psychiatry. 2020 Jul;7(7):611-627 - PubMed
  40. J Neurovirol. 2021 Feb;27(1):154-159 - PubMed
  41. JAMA. 2021 May 18;325(19):2015-2016 - PubMed
  42. Crit Rev Clin Lab Sci. 2021 Aug;58(5):297-310 - PubMed
  43. Trends Mol Med. 2021 Sep;27(9):895-906 - PubMed
  44. J Infect. 2020 Dec;81(6):e4-e6 - PubMed
  45. JAMA. 2000 Apr 19;283(15):2008-12 - PubMed
  46. Lancet Reg Health Eur. 2021 Jul;6:100122 - PubMed
  47. Clin Microbiol Infect. 2021 Jan;27(1):89-95 - PubMed
  48. Respir Med. 2021 May;181:106383 - PubMed
  49. Eur Neuropsychopharmacol. 2021 May;46:39-48 - PubMed
  50. N Engl J Med. 2021 Feb 4;384(5):481-483 - PubMed
  51. Eur J Nucl Med Mol Imaging. 2021 Aug;48(9):2823-2833 - PubMed
  52. J Clin Nurs. 2021 Jun;30(11-12):1742-1750 - PubMed
  53. Acta Paediatr. 2021 Jul;110(7):2208-2211 - PubMed
  54. J Clin Psychiatry. 2017 Jul;78(7):873-881 - PubMed
  55. Eur Respir J. 2020 Nov 26;56(5): - PubMed
  56. J Infect Dis. 2021 May 28;223(10):1671-1676 - PubMed
  57. J Psychosom Res. 2018 Nov;114:62-71 - PubMed
  58. Clin Infect Dis. 2021 Dec 6;73(11):e4058-e4063 - PubMed
  59. Chest. 2021 Jul;160(1):187-198 - PubMed
  60. Lung. 2021 Jun;199(3):249-253 - PubMed
  61. Nat Med. 2021 Apr;27(4):601-615 - PubMed
  62. JAMA. 2020 Oct 13;324(14):1381-1383 - PubMed
  63. Ann Am Thorac Soc. 2021 Nov;18(11):1912-1917 - PubMed
  64. Pan Afr Med J. 2020 Dec 01;37:289 - PubMed
  65. JAMA Netw Open. 2021 Feb 1;4(2):e210830 - PubMed
  66. CNS Spectr. 2019 Feb;24(1):154-162 - PubMed
  67. eNeurologicalSci. 2021 Mar;22:100322 - PubMed
  68. MMWR Morb Mortal Wkly Rep. 2020 Jul 31;69(30):993-998 - PubMed
  69. Eur Respir J. 2021 Apr 29;57(4): - PubMed

Publication Types