Symptom-based rehabilitation in people with post-COVID-19 condition (RELOAD study): a randomised controlled trial

Clinical Snapshot

Key Findings

• P Value: p=0.038 (3 weeks), p=0.003 (3 months)

• Effect Size: Mean difference 2.9 points (3 weeks), 4.2 points (3 months)

• Primary Outcome: SF-12 Physical Component Summary score improvement of 2.9 points at 3 weeks

• Nnt Or Sensitivity: NNT not calculable from provided data; effect size suggests modest clinical benefit

• Confidence Interval: 95% CI 0.2 to 5.7 (3 weeks), 1.5 to 6.9 (3 months)

Clinical Application

Requires specialised rehabilitation facilities and multidisciplinary teams. 3-week intensive programme may have resource implications for widespread implementation Relevant to Australian post-COVID clinics and rehabilitation services. May inform development of Medicare-funded rehabilitation programmes for long COVID patients Adults with persistent post-COVID symptoms, particularly those with fatigue, cognitive problems, or somatic symptoms lasting beyond acute infection

Abstract

RATIONALE: Post-COVID condition (PCC) is characterised by persistent symptoms that impair health-related quality of life (HRQoL); rehabilitation (REHAB) strategies remain scarce. OBJECTIVE: To investigate the effect of a symptom-based REHAB programme versus usual care on HRQoL in people with PCC. METHODS: In this single-blind randomised controlled trial, a total of 132 people with PCC were randomised to either a REHAB group or a control group, with 104 completing the trial. The REHAB group received a multimodal 3-week REHAB programme tailored to the participant's primary symptom-based group (fatigue, cognitive problems or somatic symptoms); the control group received usual care. The primary endpoint was the between-group difference in change in HRQoL, measured by the 12-item Short Form Health Survey (SF-12) physical component summary (PCS) score at 3 weeks post baseline (intervention period). Changes from baseline to a 3-month follow-up after the intervention period were also analysed as a secondary measure. Additional outcomes included mental HRQoL (SF-12 mental component summary (MCS)), depression symptoms (Patient Health Questionnaire 9 (PHQ-9)) and anxiety symptoms (Generalized Anxiety Disorder 7 (GAD-7)). RESULTS: Participants (mean age 47±12.3 years, 90.4% not hospitalised during acute SARS-CoV-2 infection, 69.2% female) in the REHAB group (n=47) showed a significantly greater improvement in PCS compared with the control group (n=57) (mean difference (Δ) 2.9 points, 95% CI 0.2 to 5.7, p=0.038) at 3 weeks post baseline. This difference remained significant at the 3-month follow-up (Δ 4.2 points, 95% CI 1.5 to 6.9, p=0.003). The REHAB group also showed significant improvements in mental HRQoL (MCS: Δ 5.7 points, 95% CI 2.0 to 9.4, p=0.003), as well as in depression symptoms (PHQ-9: Δ -2.7 points, 95% CI -4.2 to -1.2, p<0.001) and anxiety symptoms (GAD-7: Δ -2.4 points, 95% CI -3.7 to -1.1, p<0.001) at 3 weeks post baseline compared with the control group. At the 3-month follow-up, the reduction in depression symptoms remained significant, while no significant differences were observed for mental HRQoL or anxiety symptoms. CONCLUSION: A symptom-based rehabilitation programme significantly improved HRQoL in individuals with PCC after 3 weeks, with some benefits persisting at 3 months. TRIAL REGISTRATION NUMBER: NCT05172206.

References

1. 1.Schneeberger, T., Jarosch, I., Kroll, D., Gloeckl, R., Schneider, C., Ulm, B., Schwaiblmair, M., Lampert, S., Greulich, T., Schoenherr, I., Schultz, T., Schrag, T., Dennis, C. J., & Koczulla, A. R. (2026). Symptom-based rehabilitation in people with post-COVID-19 condition (RELOAD study): a randomised controlled trial. BMJ Open Respiratory Research, 13(1), e004177. https://doi.org/10.1136/bmjresp-2026-004177