Analysis of fat oxidation capacity during cardiopulmonary exercise testing indicates long-lasting metabolic disturbance in patients with post-covid-19 syndrome

Background & aims: Post-COVID-19 Syndrome (PCS) is characterized by symptoms including fatigue, reduced physical performance, dyspnea, cognitive impairment, and psychological distress. The mechanisms underlying the onset and severity of PCS point to mitochondrial dysfunction as significant contributor. This study examined fat oxidation as a function of mitochondrial capacity during exercise.

Methods: Single-center prospective cohort study during inpatient rehabilitation. Cardiopulmonary exercise testing and assessment of fatigue using questionnaires were performed at admission and discharge. Detailed spirometric breath-by-breath data were used to calculate substrate oxidation rates.

Results: Patients (N = 187; 38 % women; 49.7 ± 11.4 years) were referred to rehabilitation 253.4 ± 130.6 days after infection. Lead symptoms included fatigue/exercise intolerance (79.9 %), shortness of breath (77.0 %), and cognitive dysfunction (55.1 %). Fat oxidation capacity was disturbed in PCS patients overall (AUC: 11.3 [10.7-11.9]) compared to healthy controls (p < 0.0001), with hospitalization during acute infection predicting the level of disturbance (p < 0.0001). Low exercise capacity and high fatigue scores resulted in reduced fat oxidation (both p < 0.0001). In particular, younger males were affected by significantly reduced fat oxidation capacity (sex: p = 0.002; age: p < 0.001). Metabolic disturbance was significantly improved during exercise-based rehabilitation (AUC: 14.9 [14.4-15.4]; p < 0.0001), even for the group of younger impaired males (+44.2 %; p < 0.0001). Carbohydrate oxidation was not impaired.

Conclusions: PCS-specific restrictions in fat oxidation may indicate persistent mitochondrial dysfunction. Clinical assessment of PCS patients should include detailed breath-by-breath analysis during exercise to identify metabolic alterations especially in the group of younger males identified in this report. Exercise-based rehabilitation results in improved exercise capacity and fat oxidation and thus likely mitochondrial function.

Clinical trials: NCT06468722.