Sex-Specific Differences in Exercise-Based Rehabilitation of Patients with Long-Term Post-COVID-19 Syndrome

Introduction: Patients with Post-COVID-19 Syndrome (PCS) suffer from various symptoms including (chronic) fatigue, decreased physical performance, dyspnoea, cognitive impairment and mental/ psychological distress. Given the potential effectiveness of exercise-based rehabilitation in ameliorating physical capacity and disease burden in PCS, this study assessed the efficacy of a tailored rehabilitation program for PCS patients. In addition, we investigated sex-specific differences in rehabilitation efficiency between male and female PCS patients.

Methods: 145 PCS patients referred to inpatient rehabilitation (52 female, 93 male) underwent comprehensive clinical assessment, including symptom-limited cardiopulmonary exercise testing (CPET) at admission and discharge. For comparability, CPET data was analyzed as percent of reference adjusted for age, sex and body surface. Questionnaires (MFI-20, SF-36, WHO-5, WAI, HADS) were used for evaluating disease perception upon admission as well as at 4 weeks and 6 months follow-up. Patients’ engagement in physical therapies (strength, endurance, and respiratory muscle training), cognitive exercises, relaxation techniques, and educational sessions were documented.

Results: Patients (50.2±10.7 years, female, 47.1±12.7 years; male, 52.0±9.1 years; p=0.018) were referred to rehabilitation after a mean of 262.0±128.8 days (female, 285.5±140.6 days; male, 248.8±112.0 days; p=0.110) after acute infection. No differences between female and male patients were detected for lead symptoms such as fatigue/exercise intolerance (81.4% of patients), shortness of breath (74.5%), and cognitive dysfunction (52.4%, p≥0.458). At baseline, patients exhibited a significant limitation in physical exercise capacity at both submaximal (VT1) and peak load (VO_2peak; 73.6±15.0% of reference). Notably, female PCS patients demonstrated significantly higher relative peak exercise capacity at baseline (82.0±14.3%) compared to males (68.8±13.3%, p≤0.001). Female and male PCS patients equally improved submaximal and peak exercise capacity (p=0.001) by up to 7.0% and 3.4%, respectively and percentage of responders was comparable (VO_2peak; female, 60%; male, 58%; p=0.856). In terms of disease perception, female patients exhibited higher levels of fatigue and lower wellbeing at baseline, but showed greater improvement compared to males in overall fatigue and depression (timexgroup: p≤0.0412). Sex-specific differences were independent of age and participation in rehabilitation sessions was comparable. Overall, female and male PCS patients demonstrated improvements in fatigue, health-related quality of life (QoL, physical and mental component score) and wellbeing, as well as reductions in anxiety and depression during the rehabilitation process (all p≤0.014). Six months after discharge, workability was significantly improved, while fatigue, health-related quality of life and wellbeing remained stable.

Conclusion: Female PCS patients presented with higher initial exercise performance capacity, but elevated perceived disease burden compared to male patients. Rehabilitation outcomes were comparable between female and male patients with significant improvements in exercise capacity, health-related QoL and fatigue. We conclude that inpatient exercise-based medical rehabilitation has substantial benefits for female and male PCS patients, leading to increased workability and improved long-term QoL.