BACKGROUND: The post-COVID-19 syndrome (PCS), which can occur after acute respiratory syndrome coronavirus 2 infection, leads to restrictions in everyday activity. Our study assessed the impact of an online-guided intervention which intended to facilitate physical activity on the mental and physical capability of PCS patients. METHODS: We randomized 62 patients with PCS (20 male/ 42 female; age 46 +/- 12 years; body mass index 28.7 +/- 6.7 kg/m2) with a score >= 22 in the fatigue assessment scale (FAS) to a 3-month exercise-focused intervention (IG n = 30) or control period (CG n = 32). We assessed changes in exercise capacity (bicycle exercise test with measurements of gas exchange), fatigue, markers of health-related quality of life (HrQoL) and mental health. RESULTS: The FAS score decreased significantly in both study groups (IG: 35.1 +/- 7.4 to 31.8 +/- 8.5 points; CG: 35.6 +/- 7.4 to 32.6 +/- 7.5 points, both p < 0.01). Exercise capacity did not increase in the CG or IG (within-group changes for IG: peak oxygen uptake: 0.9 +/- 2.6 ml/min/kg, p = 0.098; peak power output: 6.1 +/- 17.8 W, p = 0.076) with no significant changes in HrQoL and work ability. Patients with a FAS score at baseline >= 35 (severe fatigue) showed no change in exercise capacity with the 3-month intervention whereas the sub-group of patients with FAS < 35 points (moderate fatigue) showed improvements, independent of the study group. CONCLUSIONS: Our 3-month intervention seems appropriate for patients with moderate fatigue, whereas those with more severe fatigue appear to be too restricted with respect to their mental or physical health status to perform exercise at a level which is sufficient to improve markers of physical performance. TRIAL REGISTRATION: German Clinical Trials Register (registration trial number: DRKS00026245) on September 2 2021.

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