On the 12th August, 2025, the following paper, ‘Mitochondrial function is impaired in long COVID patients,' was published in Annals of Medicine, and can be read on Taylor and Francis Online.
Summary
- A study comparing Long COVID patients with controls found altered mitochondrial activity in immune cells, including abnormal ATP synthase behaviour.
- Mitochondrial function correlated with symptoms and quality of life, suggesting a potential causal role that needs further large-scale investigation.
Abstract
Background
The Long COVID syndrome is a major global health problem, affecting approximately 10–20% of individuals infected with SARS-CoV-2 virus with many remaining symptomatic beyond one year. Fatigue, reduced exercise tolerance and hyperlactataemia on minimal exertion have led to the suggestion of a bioenergetic defect. We hypothesised that mitochondrial dysfunction is a pathological feature in Long COVID cases and would correlate with clinical outcome.
Methods
This prospective, case-controlled, observational study recruited 27 participants with an established diagnosis of Long COVID syndrome from a single tertiary clinic together with 16 age-matched controls aged 25–65 years. Seahorse-based mitochondrial flux analysis and bioenergetics profile of isolated peripheral blood mononuclear cells (PBMCs) was performed and correlated with clinical phenotype.
Findings
Long COVID cases had an increased baseline and ATP-induced oxygen consumption rate with a significant attenuation in tetramethylrhodamine methyl ester perchlorate fluorescence response to oligomycin. Correlations were observed between mitochondrial function and autonomic health, quality of life and time from index infection. Sex-specific differences were also observed.
Interpretation
PBMCs from Long COVID subjects exhibit an exceptional and distinctive change in ATP synthase, as it contributes to the mitochondrial membrane potential rather than using it exclusively to generate ATP. The findings suggest that the enzyme runs both forward and reverse reactions, synthesising and hydrolysing ATP. The correlation of mitochondrial function with clinical phenotype in Long COVID may indicate a causal relationship and warrants further validation in larger scale studies.
MEA Comment
Further research evidence of mitochondrial dysfunction in Long Covid from a UK based study.
Mitochondria are cellular structures that play a key role in energy production.
NB: We already have a substantial amount of good quality research evidence which demonstrates mitochondrial dysfunction in ME/CFS.
Dr Charles Shepherd,
Trustee and Hon. Medical Adviser to the ME Association,
Member of the 2018-2021 NICE guideline on ME/CFS committee,
Member of the 2002 Chief Medical Officer's Working Group on ME/CFS
