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1H and 31P MR Spectroscopy to Assess Muscle Mitochondrial Dysfunction in Long COVID
Lucy E M Finnigan1, Mark Philip Cassar1, Mehrsa Jafarpour1
1From the Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK (L.E.M.F., M.P.C., M.J., A.S., Z.A., S.N., D.J.T., B.R., L.V.); Oncology and Haematology Centre, Churchill Hospital, Oxford, UK (A.S.); Axcella Therapeutics, Cambridge, Mass (K.A.); and Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia (L.V.).
Post-COVID-19 condition (PCC) patients exhibit altered mitochondrial function, indicated by changes in phosphocreatine recovery and oxidative flux, suggesting potential mitochondrial dysfunction. However, these MR spectroscopy findings did not correlate with fatigue severity in PCC individuals.
Area of Science:
- Biomedical imaging
- Metabolic research
- Post-COVID-19 condition research
Background:
- Mitochondrial dysfunction is increasingly implicated in the persistent fatigue of post-COVID-19 condition (PCC).
- Magnetic Resonance (MR) spectroscopy offers a non-invasive method to assess in vivo mitochondrial function.
- Understanding these mechanisms is crucial for developing targeted therapies for PCC.
Purpose of the Study:
- To compare mitochondrial function between PCC patients with predominant fatigue and healthy controls using MR spectroscopy.
- To investigate the correlation between MR spectroscopic parameters of mitochondrial function and fatigue severity using the Chalder fatigue questionnaire.
Main Methods:
- Prospective, observational study involving 41 PCC patients and 29 healthy controls.
- MR spectroscopy (3-T) measured hydrogen 1 (1H) and phosphorus 31 (31P) in the gastrocnemius muscle during exercise and recovery.
- Key parameters analyzed: phosphocreatine recovery rate time constant (τPCr) and maximum oxidative flux (Qmax).
Main Results:
- PCC participants demonstrated a significantly higher τPCr (92.5s vs 51.9s, P ≤ .001), indicating slower energy replenishment.
- Maximum oxidative flux (Qmax) was significantly lower in PCC patients compared to controls (P = .008).
- No significant correlation was found between MR spectroscopic parameters (τPCr, Qmax) and fatigue scores (Chalder questionnaire).
Conclusions:
- MR spectroscopy reveals distinct differences in muscle mitochondrial energetics (τPCr and Qmax) in individuals with PCC compared to healthy controls.
- These observed alterations suggest potential mitochondrial dysfunction contributing to PCC pathophysiology.
- The study did not find a direct correlation between these specific MR spectroscopic markers and the subjective fatigue experienced by PCC patients.
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