Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2023 Sep 11;77(5):687-695.
doi: 10.1093/cid/ciad257.

Efficacy of Cognitive-Behavioral Therapy Targeting Severe Fatigue Following Coronavirus Disease 2019: Results of a Randomized Controlled Trial

Tanja A Kuut  1   2 , Fabiola Müller  1   2 , Irene Csorba  1   2 , Annemarie Braamse  1   2 , Arnoud Aldenkamp  3 , Brent Appelman  4 , Eleonoor Assmann-Schuilwerve  5 , Suzanne E Geerlings  2   6 , Katherine B Gibney  7   8 , Richard A A Kanaan  9 , Kirsten Mooij-Kalverda  10 , Tim C Olde Hartman  11 , Dominique Pauëlsen  1   2 , Maria Prins  2   6   12 , Kitty Slieker  13 , Michele van Vugt  2   6 , Stephan P Keijmel  14 , Pythia Nieuwkerk  1   2   6 , Chantal P Rovers  14 , Hans Knoop  1   2
Affiliations
Randomized Controlled Trial

Efficacy of Cognitive-Behavioral Therapy Targeting Severe Fatigue Following Coronavirus Disease 2019: Results of a Randomized Controlled Trial

Tanja A Kuut et al. Clin Infect Dis. .

Abstract

Background: Severe fatigue following coronavirus disease 2019 (COVID-19) is prevalent and debilitating. This study investigated the efficacy of cognitive-behavioral therapy (CBT) for severe fatigue following COVID-19.

Methods: A multicenter, 2-arm randomized controlled trial was conducted in the Netherlands with patients being severely fatigued 3-12 months following COVID-19. Patients (N = 114) were randomly assigned (1:1) to CBT or care as usual (CAU). CBT, targeting perpetuating factors of fatigue, was provided for 17 weeks. The primary outcome was the overall mean difference between CBT and CAU on the fatigue severity subscale of the Checklist Individual Strength, directly post-CBT or CAU (T1), and after 6 months (T2). Secondary outcomes were differences in proportions of patients meeting criteria for severe and/or chronic fatigue, differences in physical and social functioning, somatic symptoms, and problems concentrating between CBT and CAU.

Results: Patients were mainly nonhospitalized and self-referred. Patients who received CBT were significantly less severely fatigued across follow-up assessments than patients receiving CAU (-8.8 [95% confidence interval {CI}, -11.9 to -5.8]); P < .001), representing a medium Cohen's d effect size (0.69). The between-group difference in fatigue severity was present at T1 (-9.3 [95% CI, -13.3 to -5.3]) and T2 (-8.4 [95% CI, -13.1 to -3.7]). All secondary outcomes favored CBT. Eight adverse events were recorded during CBT, and 20 during CAU. No serious adverse events were recorded.

Conclusions: Among patients, who were mainly nonhospitalized and self-referred, CBT was effective in reducing fatigue. The positive effect was sustained at 6-month follow-up.

Clinical trials registration: Netherlands Trial Register NL8947.

Keywords: COVID-19; cognitive-behavioral therapy; fatigue; long COVID.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest. F. M. reports funding from the Nederlands Kenniscentrum Chronische Vermoeidheid (NKCV) Foundation. C. P. R. reports grants as a payment to institution by the present study, the European Union Horizon 2020 Research and Innovation Framework Programme, and the Michael J. Fox Foundation; and has served as a member of the committee “Pandemic Preparedness Plan” of the Royal Netherlands Academy of Arts and Sciences and a member of the committee “Long-term effects of COVID-19” of the Health Council of the Netherlands. K. B. G. reports salary support (investigator grant [MRF1193727] 2021–2025) by the MRFF/NHMRC, Australia; grants from the Partnership Project (APP1196396 2020–2023, APP152807) and an Early Career Fellowship (APP1120816) by the NHMRC; Faculty of Medicine, Dentistry and Health Sciences (MDHS) Research Grant Support Scheme 2020 by the University of Melbourne; a Research Establishment Fellowship 2020 by the Royal Australasian College of Physicians–GlaxoSmithKline; Seed Funding 2019 by the Melbourne Children's Research Institute; royalties for textbook (Manual of Travel Medicine Edition 4) by Springer Nature Singapore; and being a member of the Australian Technical Advisory Group of Immunisation and an expert member (representing the Australasian Society of Infectious Diseases) of the Communicable Diseases Network Australia. R. A. A. K. reports grants or contracts from MRFF/NHMRC, Mindgardens Neuroscience Network, and Austin Medical Research Foundation; and has served as advisory board member of the Psychae Institute, director of the Functional Neurological Disorder Society, director of the International Neuropsychiatry Association, and member of the Biotoxin-Related Illness Advisory Committee, Australian Department of Health. H. K. was supported for this study by the Netherlands Organization for Health Research and Development (ZonMw: project number 10430012010025, research program COVID-19), with payments made to institution; and grants from ZonMw to conduct research into long COVID and post-Lyme symptoms, from the Dutch Cancer Society, Multiple Sclerose research, Pfizer, and NKCV Foundation. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Graphical Abstract
Graphical Abstract
This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/efficacy-of-cognitive-behavioral-therapy-targeting-severe-fatigue-following-covid-19-results-of-a-randomized-controlled-trial-fdaaee2d-1681-4e6e-a423-2a80a129b816
Figure 1.
Figure 1.
Flowchart of enrollment and randomization of patients. *One self-referred patient was screened for eligibility by a physician of a participating hospital. Abbreviations: CAU, care as usual; CBT, cognitive-behavioral therapy; COVID-19, coronavirus disease 2019; PTSD, posttraumatic stress disorder; T1, 19 weeks postrandomization; T2, 6 months after T1.
Figure 2.
Figure 2.
Checklist Individual Strength–fatigue scores and standard errors from baseline to the posttreatment assessment for the cognitive-behavioral therapy group and the care as usual group. Abbreviations: CAU, care as usual; CBT, cognitive-behavioral therapy; CIS, Checklist Individual Strength; T0, baseline; T1, 19 weeks postrandomization; T2, 6 months after T1.
Figure 3.
Figure 3.
Changes in Checklist Individual Strength–fatigue scores from baseline to the posttreatment assessment for the cognitive-behavioral therapy group (A) and the care as usual group (B). The score of 1 patient in the care as usual group dropped below 35 between screening and baseline. 2These points are double as 2 patients had the same scores. Figures were created using the Leeds reliable change index calculator [29]. Abbreviations: CI, confidence interval; CIS, Checklist Individual Strength; RCI, reliable change index; T0, baseline; T1, 19 weeks postrandomization.
See this image and copyright information in PMC

Comment in

References

    1. Salamanna F, Veronesi F, Martini L, Landini MP, Fini M. Post-COVID-19 syndrome: the persistent symptoms at the post-viral stage of the disease. A systematic review of the current data. Front Med 2021; 8:653516. - PMC - PubMed
    1. 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 2022; 101:93–135. - PMC - PubMed
    1. Han Q, Zheng B, Daines L, Sheikh A. Long-term sequelae of COVID-19: a systematic review and meta-analysis of one-year follow-up studies on post-COVID symptoms. Pathogens 2022; 11:269. - PMC - PubMed
    1. Verveen A, Wynberg E, van Willigen HDG, et al. Severe fatigue in the first year following SARS-CoV-2 infection: a prospective cohort study. Open Forum Infect Dis 2022; 9:ofac127. - PMC - PubMed
    1. Huang L, Li X, Gu X, et al. Health outcomes in people 2 years after surviving hospitalisation with COVID-19: a longitudinal cohort study. Lancet Respir Med 2022; 10:863–76. - PMC - PubMed

Publication types