FUNCTIONAL AND MORHOLOGICAL DIFFERENCES OF MUSCLE MITOCHONDRIA IN CFS AND POST-COVID SYNDROME

PURPOSE: Patients suffering from Chronic Fatigue Syndrome (CFS) or Post-COVID (PCS) exhibit a reduced physiological performance capability with detrimental effects on quality of life and exercise capacity. Impaired mitochondrial function and morphology may play a pivotal role. Muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity and mitochondrial morphology was assesed in 15 CFS and 15 PCS patients and 11 healthy controls (HC). METHODS: After muscle biopsy, mitochondrial OXPHOS capacity was measured in permeabilized muscle fibers of the m. quadriceps femoris by high-resolution respirometry. Mitochondrial morphology (subsarcolemmal/intermyofibrillar mitochondrial form/cristae/diameter/circumference/area) and content (number and proportion/cell) was assessed by electron microscopy and analyzed by ImageJ. The Canadian Consensus Criteria for determining CFS were used to include CFS (10f/5 m; age 36.1 ± 11.6 years; BMI 25.0 ± 3.6 kg/m2) and PCS (13f/2 m; age 40.5 ± 13.2 years; BMI 21.9 ± 3.9 kg/m2). Robust one-way ANOVAs for OXPHOS, post-hoc tests and correlation analysis for morphology/content. RESULTS: Normal OXPHOS capacity of complex I was reduced in PCS compared to HC (P = 0.031), and PCS showed lower values for all other OXPHOS assessments compared to CFS and HC (ns). While the subsarcolemmal area, volume/cell, diameter and perimeter was higher in PCS vs. CFS, no difference was observed for these respective variables regarding intermyofibrillar mitochondria. Both the intermyofibrillar and subsarcolemmal cristae score was higher in PCS compared to CFS (P < 0.001), indicating a decreased morphological stability and impaired mitochondrial structure in CFS and a positive association between cristae score and cristae form. CONCLUSIONS: Although CFS and PCS exhibit increased fatigue and mitochondrial capacity is impaired in both populations, the progressed pathological morphological changes in CFS suggests structural changes due to prolonged inactivity or unknown molecular causes compared to a probably direct virus-induced immunology alterations and damage in PCS. The decreased OXPHOS capacity in PCS may due to physical inactivity, the lower complex I activity suggests a target to its first role in the electron gradient machinery and importance in energy production. Grant of the ministry of science Baden-Wuertemberg