Can Cognitive Behavioral Therapy Target Severe Fatigue Following COVID-19?

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A recent study published in the Clinical Infectious Diseases Journal examined the efficacy of cognitive behavioral therapy (CBT) for severe fatigue after coronavirus disease 2019 (COVID-19).

Study: Efficacy of cognitive behavioral therapy targeting severe fatigue following COVID-19: results of a randomized controlled trial. Image Credit: fizkes/


Research attention has been increasing on the long-term sequelae of COVID-19, known as long COVID. Fatigue, one of the most common long COVID symptoms, could often be severe. In addition, some patients still report fatigue up to two years post-acute COVID-19.

Therefore, evidence-based interventions are necessary, given that post-COVID-19 fatigue affects millions of individuals worldwide.

Severe, persistent fatigue is common after infectious diseases. Cognitive behavioral factors are associated with fatigue persistence across long-term medical conditions.

While CBT has effectively alleviated fatigue in patients with long-term conditions or post-infection fatigue, it has yet to be assessed in those with fatigue post-COVID-19.

About the study

In the present study, researchers investigated the efficacy of CBT for severe fatigue in patients after COVID-19 in a multicenter randomized controlled trial in the Netherlands. Participants were eligible if diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, severely fatigued, and functionally impaired within three-12 months after infection.

Physicians from six hospitals recruited patients. Subjects were randomized 1:1 to CBT or care at usual (CAU) using a web-based system. They were stratified by hospitalization status and dyspnea. Eligible subjects completed baseline (T0) questionnaires before randomization. CBT was planned for 17 weeks and initiated two weeks post-randomization. 

Participants completed additional questionnaires (T1) at 19 weeks post-randomization and six months after that (T2). The authors developed the CBT for fatigue post-COVID-19, termed ‘Fit after COVID,’ by adapting from existing protocols.

They addressed disrupted sleep-wake patterns, perceived low social support, fears or worries about COVID-19, unhelpful beliefs regarding fatigue, low activity levels, poor coping with pain, and problems with the psychological processing of COVID-19.

CAU participants were not restricted from seeking care for fatigue, including psychological interventions. Likewise, there were no restrictions for CBT subjects other than multidisciplinary rehabilitation.

The main outcome was fatigue severity differences between CBT and CAU groups across T1 and T2, assessed using the fatigue subscale of checklist individual strength (CIS-fatigue).

Secondary outcomes included the between-group difference in the proportion of subjects who were no longer severely or chronically fatigued and reported a reliable change in fatigue at T1 and T2.

The two groups were also compared for physical and social functioning, somatic symptom severity, and concentration difficulties. In addition, adverse events (AEs) and serious AEs (SAEs) were recorded based on self-reports or observations by therapists or staff.


Over 700 patients were screened for eligibility between November 2020 and September 2021. Of these, 114 patients were randomized to CBT or CAU. Most patients (89%) were not hospitalized during COVID-19. Only one patient was not infected before vaccination. The mean duration of CBT was 18.7 weeks, with nearly 12 interactions, on average, between patients and therapists.

The researchers observed an overall difference of -8.8 in the fatigue severity score between groups, favoring CBT with a medium effect size. The mean difference in the score was -9.3 at T1 and -8.4 at T2.

Secondary outcomes favored CBT; most patients in the CBT group reported a reliable change in fatigue and not being severely or chronically fatigued, compared to a small proportion of patients in the CAU group. There were no indications that fatigue deteriorated after CBT.

The average difference in physical functioning score was 7.1 between groups, favoring CBT with a small effect size. The group difference in social functioning score was -6.6, favoring CBT with a medium effect size.

Similarly, the group differences in scores related to somatic symptoms and concentration problems favored CBT, with a small or medium effect size. Eight AEs were documented in seven patients in the CBT group, and 20 adverse events (AEs) occurred in 14 patients in the CAU group. Six AEs were possibly CBT-related. No SAEs were recorded.


The trial showed that patients with severe fatigue within three-12 months post-COVID-19 were significantly less fatigued following CBT than post-CAU.

The positive effects of CBT were found to be sustained for six months post-intervention. Moreover, subjects in the CBT group were also less often severely or chronically fatigued, with less severe somatic symptoms, fewer concentration problems, and improved physical or social functioning.

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