Brain and muscle chemistry in myalgic encephalitis/chronic fatigue syndrome (ME/CFS) and long COVID: a 7T magnetic resonance spectroscopy study.

Publication date: Jul 12, 2025

Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a common debilitating medical condition, whose main symptoms – fatigue, post-exertional malaise and cognitive dysfunction – are also present in many cases of long COVID. Magnetic resonance spectroscopy (MRS) allows the insight into their pathophysiology through exploration of a range of biochemicals putatively relevant to aetiological processes, in particular mitochondrial dysfunction and energy metabolism. 24 patients with ME/CFS, 25 patients with long COVID and 24 healthy controls (HC) underwent brain (pregenual and dorsal anterior cingulate cortex, respectively, pgACC and dACC) and calf muscle MRS scanning at 7 Tesla, followed by a computerised cognitive assessment. Compared to HC, ME/CFS patients had elevated levels of lactate in both pgACC and dACC, while long COVID patients had lowered levels of total choline in dACC. By contrast, skeletal muscle metabolites at rest did not significantly differ between the groups. The changes in lactate in ME/CFS are consistent with the presence of energetic stress and mitochondrial dysfunction. A reduction in total choline in long COVID is of interest in the context of the recently reported association between blood clots and ‘brain fog’, and earlier animal studies showing that choline might prevent intravascular coagulation. Importantly, differences in findings between ME/CFS and long COVID suggest that the underlying neurobiological mechanisms, while leading to similar clinical presentations, may differ. An important implication is that patients with ME/CFS and those with fatigue in the course of long COVID should not be studied as a single group, at least until the mechanisms are better understood.

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Concepts	Keywords
Mitochondrial	Brain
Neurobiological	Cfs
Pgacc	Choline
Rest	Chronic
Tesla	Covid
	Dacc
	Dysfunction
	Encephalitis
	Fatigue
	Long
	Magnetic
	Muscle
	Myalgic
	Resonance
	Syndrome

Semantics

Type	Source	Name
disease	MESH	encephalitis
disease	MESH	chronic fatigue syndrome
disease	MESH	long COVID
disease	MESH	cognitive dysfunction
disease	MESH	mitochondrial dysfunction
pathway	REACTOME	Metabolism
drug	DRUGBANK	Choline
disease	MESH	blood clots
disease	MESH	‘brain fog
drug	DRUGBANK	Tropicamide
disease	IDO	acute infection
disease	MESH	COVID 19
disease	MESH	viral infections
disease	MESH	emotional stress
disease	MESH	syndromes
drug	DRUGBANK	Coenzyme M
disease	MESH	muscle fatigue
drug	DRUGBANK	Glutathione
drug	DRUGBANK	Creatine
disease	MESH	oxidative stress
disease	MESH	inflammation
disease	IDO	blood
drug	DRUGBANK	Carnosine
disease	MESH	abnormalities
disease	IDO	production
drug	DRUGBANK	L-Glutamine
disease	MESH	panic attack
drug	DRUGBANK	Methionine
disease	IDO	history
disease	MESH	infection
disease	MESH	depression
disease	MESH	anxiety
disease	MESH	Schizophrenia
drug	DRUGBANK	Flunarizine
drug	DRUGBANK	Water
disease	IDO	quality
drug	DRUGBANK	L-Aspartic Acid
drug	DRUGBANK	Ascorbic acid
drug	DRUGBANK	N-acetylsulfanilyl chloride
drug	DRUGBANK	Phosphocreatine
drug	DRUGBANK	Butyric Acid
drug	DRUGBANK	gamma-Aminobutyric acid
drug	DRUGBANK	Dextrose unspecified form
drug	DRUGBANK	Glutamic Acid
drug	DRUGBANK	Inositol
drug	DRUGBANK	1-naphthaleneacetic acid
drug	DRUGBANK	Taurine
disease	IDO	macromolecule
drug	DRUGBANK	Levocarnitine
pathway	REACTOME	Glycolysis
pathway	KEGG	Oxidative phosphorylation
drug	DRUGBANK	Oxygen
disease	MESH	hypoxia
drug	DRUGBANK	NADH
pathway	KEGG	Metabolic pathways
disease	MESH	Neuroinflammation
drug	DRUGBANK	ATP
disease	MESH	disseminated intravascular coagulation
disease	MESH	stroke
disease	MESH	acidosis
disease	IDO	process
pathway	REACTOME	Fatty acids
disease	MESH	sedentary lifestyle
disease	IDO	symptom
drug	DRUGBANK	Acetylcarnitine
disease	MESH	orthostatic intolerance
disease	MESH	sore throat
disease	MESH	multiple sclerosis
disease	MESH	sequelae
disease	MESH	neglected disease
disease	MESH	anxiety disorder
disease	MESH	major depressive disorder
disease	MESH	fibromyalgia
disease	MESH	nitrosative stress
drug	DRUGBANK	Gold
disease	MESH	psychotic disorders
drug	DRUGBANK	Iron
disease	IDO	algorithm
disease	MESH	endotoxemia
disease	MESH	acute ischemic stroke
pathway	REACTOME	Reproduction

Original Article

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