1H and 31P MR Spectroscopy to Assess Muscle Mitochondrial Dysfunction in Long COVID, 2024, Finnigan et al

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

Lucy E. M. Finnigan, Mark Philip Cassar, Mehrsa Jafarpour, Antonella Sultana, Zakariye Ashkir, Karim Azer, Stefan Neubauer, Damian J. Tyler, Betty Raman, Ladislav Valkovič

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, τPCr) and maximum oxidative flux, also known as mitochondrial capacity (hereafter, Qmax), 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 τPCr (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 Qmax 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 τPCr and Qmax compared with healthy controls, suggesting potential mitochondrial dysfunction. This finding did not correlate with fatigue scores.

Link | PDF (Radiology) [Open Access]

 

The abstract doesn't mention it, but they also found low carnosine. From the paper:

Key Results

■ In this prospective study of 41 participants with post–COVID-19 condition (PCC) and 29 healthy controls, proton and phosphorus MR spectroscopy revealed a higher phosphocreatine recovery rate time constant (92.5 seconds ± 35.3 vs 51.9 seconds ± 31.9 [P < .001]; mean difference, 40.6 seconds [P ≤ .001]) and lower mitochondrial capacity (mean difference, 0.16 mmol/L per second; P = .008) in participants with PCC.

■ Participants with PCC showed higher resting phosphocreatine (mean difference, 4.10 mmol/L; P = .03) and lower carnosine (mean difference, 1.15 mmol/L; P = .007) levels compared with controls.

■ No correlations were found between the Chalder fatigue questionnaire (CFQ-11) scores and MR spectroscopic parameters linked to phosphocreatine recovery (r ≤ 0.25 and P ≥ .10 for all variables).

 

There's an editorial for this journal issue that discusses this study, but it's behind a paywall so I can only see the first page, and it's in image format so I can't copy text.

Power Outage: Mitochondrial Dysfunction in Long COVID Measured Using 1H and 31P MR Spectroscopy, 2024, Parraga et al

 

Key quotes from the editorial —

(I think we would just say the CFQ is useless.)

 

Interesting! Anyone know if something similar has been done in ME?

 

Not quite the same, I think, although there have been some 31P NMR studies: looking around I found this review article from 2003 - "In vivo magnetic resonance spectroscopy in chronic fatigue syndrome" - that contains a number of relevant, if old, references:

https://www.sciencedirect.com/science/article/abs/pii/S0952327804000560

One reference was this 1992 31P NMR study: "Skeletal Muscle Metabolism in the Chronic Fatigue Syndrome: In Vivo Assessment by 31P Nuclear Magnetic Resonance Spectroscopy" (Chest, December 1992), which found changes in PCr (phosphocreatine), Pi (inorganic phosphate) & in pH - old 1988 criteria:

https://www.sciencedirect.com/science/article/abs/pii/S0012369216408469

 

Just quickly, here are some potentially relevant historic refs (includes some from Nightsong) —

Muscle metabolism with blood flow restriction in chronic fatigue syndrome (2004, Journal of Applied Physiology)

In vivo magnetic resonance spectroscopy in chronic fatigue syndrome (2004, Prostaglandins, Leukotrienes and Essential Fatty Acids)

Blood flow and muscle metabolism in chronic fatigue syndrome (2003, Clinical Science)

Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle (1998, Neuromuscular Disorders)

Skeletal muscle bioenergetics in the chronic fatigue syndrome. (1993, Journal of Neurology, Neurosurgery & Psychiatry)

Skeletal Muscle Metabolism in the Chronic Fatigue Syndrome: In Vivo Assessment by 31P Nuclear Magnetic Resonance Spectroscopy (1992, CHEST)

Excessive Intracellular Acidosis Of Skeletal Muscle On Exercise In A Patient With A Post-Viral Exhaustion/Fatigue Syndrome: A 31P Nuclear Magnetic Resonance Study (1984, The Lancet)

---

Non ME/CFS-specific —

Insights into muscle diseases gained by phosphorus magnetic resonance spectroscopy (2000, Muscle & Nerve)

Abnormal oxidative metabolism in exercise in exercise intolerance of undetermined origin (1997, Neuromuscular Disorders)

Quantitative analysis by 31P magnetic resonance spectroscopy of abnormal mitochondrial oxidation in skeletal muscle during recovery from exercise (1993, NMR in Biomedicine)

Relationships between in vivo and in vitro measurements of metabolism in young and old human calf muscles (1993, Journal of Applied Physiology)