1H and 31P MR Spectroscopy to Assess Muscle Mitochondrial Dysfunction in Long COVID.

Background Emerging evidence suggests mitochondrial dysfunction may play a role in the fatigue experienced by individuals with post-COVID-19 condition (PCC), commonly called long COVID, which can be assessed using MR spectroscopy. Purpose To compare mitochondrial function between participants with fatigue-predominant PCC and healthy control participants using MR spectroscopy, and to investigate the relationship between MR spectroscopic parameters and fatigue using the 11-item Chalder fatigue questionnaire. Materials and Methods This prospective, observational, single-center study (June 2021 to January 2024) included participants with PCC who reported moderate to severe fatigue, with normal blood test and echocardiographic results, alongside control participants without fatigue symptoms. MR spectroscopy was performed using a 3-T MRI system, measuring hydrogen 1 (¹H) and phosphorus 31 (³¹P) during exercise and recovery in the gastrocnemius muscle. General linear models were used to compare the phosphocreatine recovery rate time constant (hereafter, τ_PCr) and maximum oxidative flux, also known as mitochondrial capacity (hereafter, Q_max), between groups. Pearson correlations were used to assess the relationship between MR spectroscopic parameters and fatigue scores. Results A total of 41 participants with PCC (mean age, 44 years ± 9 [SD]; 23 male) (mean body mass index [BMI], 26 ± 4) and 29 healthy control participants (mean age, 34 years ± 11; 18 male) (mean BMI, 23 ± 3) were included in the study. Participants with PCC showed higher resting phosphocreatine levels (mean difference, 4.10 mmol/L; P = .03). Following plantar flexion exercise in situ (3-5 minutes), participants with PCC had a higher τ_PCr (92.5 seconds ± 35.3) compared with controls (51.9 seconds ± 31.9) (mean difference, 40.6; 95% CI: 24.3, 56.6; P ≤ .001), and Q_max was higher in the control group, with a mean difference of 0.16 mmol/L per second (95% CI: 0.07, 0.26; P = .008). There was no correlation between MR spectroscopic parameters and fatigue scores (r ≤ 0.25 and P ≥ .10 for all). Conclusion Participants with PCC showed differences in τ_PCr and Q_max compared with healthy controls, suggesting potential mitochondrial dysfunction. This finding did not correlate with fatigue scores. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Parraga and Eddy in this issue.