Maximal oxidative capacity during exercise is associated with muscle power output in patients with [long Covid], 2023, Ramírez-Vélez et al.

[SNT Gatchaman]

Maximal oxidative capacity during exercise is associated with muscle power output in patients with long coronavirus disease 2019 COVID-19 syndrome. A moderation analysis
Robinson Ramírez-Vélez; Sergio Oscoz-Ochandorena; Yesenia García-Alonso; Nora García-Alonso; Gaizka Legarra-Gorgoñon; Julio Oteiza; Ander Ernaga Lorea; Mikel Izquierdo; María Correa-Rodríguez

Background & aims
Long COVID syndrome (LCS) involves persistent symptoms experienced by many patients after recovering from coronavirus disease 2019 (COVID-19). We aimed to assess skeletal muscle energy metabolism, which is closely related to substrate oxidation rates during exercise, in patients with LCS compared with healthy controls. We also examined whether muscle power output mediates the relationship between COVID-19 and skeletal muscle energy metabolism.

Methods
In this cross-sectional study, we enrolled 71 patients with LCS and 63 healthy controls. We assessed clinical characteristics such as body composition, physical activity, and muscle strength. We used cardiopulmonary exercise testing to evaluate substrate oxidation rates during graded exercise. We performed statistical analyses to compare group characteristics and peak fat oxidation differences based on power output.

Results
The two-way analysis of covariance (ANCOVA) results, adjusted for covariates, showed that the patients with LCS had lower absolute maximal fatty acid oxidation (MFO), relative MFO/fat free mass (FFM), absolute carbohydrates oxidation (CHox), relative CHox/FFM, and oxygen uptake (V˙˙O2) at maximum fat oxidation (g min−1) than the healthy controls (P < 0.05). Moderation analysis indicated that muscle power output significantly influenced the relationship between LCS and reduced peak fat oxidation (interaction β = −0.105 [95% confidence interval −0.174; −0.036]; P = 0.026). Therefore, when muscle power output was below 388 W, the effect of the LCS on MFO was significant (62% in our study sample P = 0.010). These findings suggest compromised mitochondrial bioenergetics and muscle function, represented by lower peak fat oxidation rates, in the patients with LCS compared with the healthy controls.

Conclusions
The patients with LCS had lower peak fat oxidation during exercise compared with the healthy controls, potentially indicating impairment in skeletal muscle function. The relationship between peak fat oxidation and LCS appears to be mediated predominantly by muscle power output. Additional research should continue investigating LCS pathogenesis and the functional role of mitochondria.


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[SNT Gatchaman]

In this study, we selected patients with LCS to investigate the physiopathology of exercise intolerance. This approach allowed us to simultaneously assess muscular fitness and MFO [maximal fatty acid oxidation] during exercise as indirect measures of the oxidative capacity. This study provides evidence of metabolic and functional impairments of muscle oxidative metabolism in patients with long COVID compared with healthy controls. We also report preliminary data suggesting the MFO-LCS association may be influenced by lower body muscle power output.

Prior research[1] reported the peripheral limitation to exercise is indicated by impairment in skeletal muscle function underlined by lower in vivo fractional O2 extraction and impaired muscle oxidative capacity, substantial reductions in biomarkers of mitochondrial function and content, and overall reduced mitochondrial sensitivity to adenosine diphosphate in post-acute sequelae of COVID-19. Thus, we can speculate that compared with the healthy controls, the patients with LCS presented more damaged mitochondria.

Our findings align with the observations made by Boer et al.[2], who reported decreased MFO during exercise in patients with LCS. This supports the notion that low fat oxidation and altered lactate production may contribute to the functional limitations experienced by patients with LCS. Boer et al. proposed that dysfunctional mitochondria, exhibiting a reduced lipid oxidation capacity and a premature shift from fat to carbohydrate oxidation, may underlie these findings.

At the molecular level, a reduction in mitochondrial function occurs as a result of the following changes: (i) lower fractional O2 extraction and impaired muscle oxidative capacity, (ii) substantial reductions in biomarkers of mitochondrial function and content, and (iii) inflammation may also alter mitochondrial dynamics.

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[1] Structural and functional impairments of skeletal muscle in patients with post-acute sequelae of SARS-CoV-2 infection (2023, Journal of Applied Physiology)

[2] Decreased Fatty Acid Oxidation and Altered Lactate Production during Exercise in Patients with Post-acute COVID-19 Syndrome (2021, American Journal of Respiratory and Critical Care Medicine)