Brief Outpatient Rehabilitation Program for Post-COVID-19 Condition: A Randomized Clinical Trial

Abstract

Importance: Post-COVID-19 condition (PCC) is emerging as a common and debilitating condition with few treatment options.

Objective: To assess the effectiveness of a brief outpatient rehabilitation program based on a cognitive and behavioral approach for patients with PCC.

Design, setting, and participants: Patients with mild to moderate PCC were randomized 1:1 to an established transdiagnostic rehabilitation program or care as usual at a single referral center recruiting from the region of the South-Eastern Norway Regional Health Authority. Participants were followed up after treatment completion and 12 months after enrollment using participant-reported outcome measures. Data were collected from February 22, 2022, until April 15, 2024. Intention-to-treat analysis was performed.

Intervention: The program consisted of 2 to 8 outpatient encounters with approximately 2 to 6 weeks between each encounter. The intervention was theoretically grounded in the cognitive activation theory of stress, and physicians and physiotherapists were trained in cognitive and behavioral approaches with targeted negative stimuli and response outcome expectancies being particularly important.

Main outcomes and measures: Participant-reported physical function assessed by the Short-Form Health Survey 36 Physical Function Subscale (SF-36-PFS) served as the primary outcome. Secondary outcome measures were the remaining subscales of the SF-36, return to work self-efficacy and symptom scores on fatigue, postexertional malaise, breathlessness, cognitive difficulties, sleep problems, anxiety and depression symptoms, and smell and taste abnormalities. Safety measures included primary health care contacts; hospital admissions; initiation of pharmacologic and/or nonpharmacologic therapy; occurrence of novel disease, illness, or other health problems; worsening of selected key symptoms; working abilities; and thoughts of suicide.

Results: A total of 473 patients with mild to moderate PCC were assessed for eligibility (n = 364 physician referred; n = 109 self-referred); 314 were included (225 females [72%]; mean [SD] age, 43 [12] years) and 231 completed the primary end point evaluation. The SF-36-PFS scores improved statistically and clinically significantly in the intervention group (score difference between groups, 9.2; 95% CI, 4.3-14.2; P < .001; Cohen d = 0.43; intention-to-treat analysis). The effect was sustained over time. Most secondary and safety measures favored the intervention.

Conclusions and relevance: In this randomized clinical trial, a brief outpatient rehabilitation program with a cognitive and behavioral approach in patients with PCC was effective and safe. This trial adds to the evidence supporting such interventions in routine clinical care. Future research should investigate which elements of this approach are the most effective and identify subgroups for which the current treatment is most relevant.

Trial registration: ClinicalTrials.gov Identifier: NCT05196451.

Figure 1.. Study Design and Overview

Loss to follow-up includes primary end point missing; participants with no response after baseline assessment, first follow-up after completion of the intervention (approximately 6 months after inclusion), and second follow-up approximately 6 months after completion of the intervention (approximately 12 months after inclusion); and protocol deviations. Study drop out includes participants with active withdrawal from the study.

Figure 2.. Intervention Effect on the Primary Outcome, Intention-to-Treat Analysis Featuring Multiple Imputation

End of treatment was the primary end point. Dots and squares represent estimated marginal means; error bars indicate 95% CIs, using analysis of covariance modeling. SF-36-PFS indicates Health Survey 36 Physical Function Subscale.