Clinical Question

Does cognitive behavior therapy (CBT) improve fatigue in patients with long COVID?

Bottom Line

CBT offers significant improvement in symptoms vs. usual care in patients with severe fatigue for at least three months after having COVID-19. (Level of Evidence = 1b)

Synopsis

Severe fatigue is a prominent and potentially disabling component of post–COVID-19 condition, or long COVID. The trial identified 114 Dutch adults with severe fatigue beginning with, or worsened by, COVID-19 and persisting for three to 12 months after onset of infection. They were randomized to a mean of 18 weeks of CBT or usual care. The groups were balanced at baseline, with a mean age of 46 years, and 11% had been hospitalized for COVID-19, 99% were unvaccinated, and 73% were female. Analysis was by intention to treat, with only three or four patients lost to follow-up in each group. The CBT intervention included goal setting, targeting a regular sleep-wake pattern, developing helpful thinking patterns, developing social support, implementing graded increases in activity, and several other components. It was delivered via online modules or telemedicine because of the pandemic. More details about the intervention can be found in an appendix to the study. The primary outcome was the score on the 20-item Checklist Individual Strength (CIS), with higher scores indicating worse fatigue (range = 8 to 56). At baseline, this score was 48 points in both groups. Clinical response was evaluated at 19 weeks (end of treatment) and at 26 weeks. The difference in fatigue scores at 19 weeks (−9.3 points; 95% CI, −13.2 to −5.3) and 26 weeks (−8.4 points; 95% CI, −13.1 to −3.7) both favored CBT and would be considered clinically significant. The percentage of patients who no longer had severe fatigue (CIS score < 35 points) was higher in the CBT group at 26 weeks (63% vs. 26%; P < .001; number needed to treat = 3). Other secondary outcomes also favored CBT, and no serious adverse events occurred.