Background: Post-COVID (PC) is characterized by prolonged symptoms following a COVID-19 infection, with Post-Exertional Malaise (PEM) being a feature with a large negative impact on quality of life. Mitochondrial dysfunction has previously been related to PEM-related symptoms. This study non-invasively investigates the in-vivo mitochondrial oxygenation (mitoPO2) and mitochondrial oxygen consumption (mitoVO2) in PC patients experiencing PEM compared to convalescent controls using the COMET device.

Methods: We conducted a comparative, non-randomized, observational study with 24 PC patients and 20 convalescent controls. MitoPO2 and mitoVO2 were measured at baseline, after short exercise, and after 10 minutes of recovery. Linear mixed models assessed the effects of exercise and recovery on mitoPO2 and mitoVO2. PROMs related to tiredness, PEM, and function were evaluated for explainability of mitoPO2 heterogeneity in PC participants using Spearman correlations.

Results: No significant differences were found between the PC and control groups in mitoPO2 and mitoVO2 (p > 0.05). Exercise led to a significant decrease in mitoPO2 (p < 0.001), which recovered after 10 minutes. No significant differences were observed between groups regarding the effects of exercise and recovery (p > 0.05). A large variance in mitoPO2 was noted in the PC group, suggesting heterogeneity within this population. Additionally, mitoVO2 increased significantly after recovery in both groups, with no significant group differences.

Conclusion: The study implies that while mitoPO2 decreases significantly after exercise and mitoVO2 increases significantly after recovery, both do not differ significantly between PC patients and controls. However, the observed variance in mitoPO2 after exercise and recovery among PC patients suggests varying disease mechanisms related to oxygen supply. Future research should focus on longitudinal assessments, home-based measurements, and exploring alternative methods to assess mitochondrial and microcircular function to better understand these findings and address the limitations of the current study.