Researchers
Kiran Thapaliya, Sonya Marshall-Gradisnik , Maira Inderyas, Leighton Barnden
Institution
Griffith University, Gold Coast, Queensland, Australia
Publication
Brain, Behavior, & Immunity – Health, 2025 November 25; 50:101142
Key findings
- MRI brain scans were performed in people with long COVID, healthy people who had recovered from COVID-19, and healthy controls with no history of COVID-19 infection.
- Altered myelin signal intensity, abnormal tissue microstructure and imbalanced neurochemicals were identified in people with long COVID.
- Myelin surrounds nerve cells and is important to ensure efficient neural function.
- There was an association between myelin content and measures of physical and cognitive function.
- These findings provide evidence that COVID-19 has long-term effects on brain function.
About the study
Leighton Barnden’s group at Griffith University in Australia have been conducting a series of studies (funded by ME Research UK) using imaging to explore brain structure and function in people with ME/CFS and those with long COVID.
The cognitive problems (or brain fog) experienced by people with these conditions suggest abnormalities in brain function, and this has been borne out by the group’s findings to date.
The researchers have so far reported brainstem volume changes (correlating with pain and breathing difficulty), impaired functional connectivity between specific brain regions, raised brain neurochemical levels and alterations in the hippocampus (involved in memory and learning).
Their most recent study looked at three measures providing information on different aspects of brain structure and function, this time focusing on individuals with long COVID.
- The myelin sheath is a protective membrane surrounding nerve cells (or neurons) which is important for ensuring that electrical impulses travel quickly and efficiently between them.
- The tissue microstructure of the brain refers to the complex combination of different neurons and support cells in the brain, as well as their extensions, related immune cells and myelin.
- Finally, brain neurochemicals are chemical messengers that transmit signals between neurons, and from neurons to their target tissues.
What did they do?
The aim of the study was to use magnetic resonance imaging to assess myelin signal intensity, tissue microstructural changes and brain neurochemical levels in 19 people with long COVID, 12 people who had fully recovered from COVID-19 infection without any ongoing symptoms, and 16 healthy control subjects with no history of COVID-19 infection.
Images of the brain were obtained using magnetic resonance imaging, from which the researchers obtained a variety of different measures.
- T1- and T2-weighted images highlight fat and water, respectively, and in this study were used to assess the myelin signal.
- Diffusion-weighted images map the microscopic movement of water molecules, and were used here to assess tissue microstructure.
- Spectroscopy techniques which measure metabolically active molecules were used to estimate brain neurochemical levels.
The various measures obtained were then compared between the three participant groups to determine whether there were any abnormalities in the long COVID group.
What did they find?
The myelin signal was significantly higher in people with long COVID than in healthy controls, both in a region of the brain that regulates motor function, and in a region involved in memory and cognition.
The researchers suggest that this finding may indicate remyelination in these areas, which would be necessary to re-establish neural function after demyelination due to infection.
It is worth noting that they previously reported similar results in people with ME/CFS.
The myelin signal was also higher in healthy people who had recovered from COVID-19, compared with both healthy controls and individuals with long COVID, and this was the case in a number of different brain regions.
Furthermore, the intensity of the myelin signal was significantly correlated with clinical symptoms including physical and cognitive function.
In people with long COVID, a lower myelin signal was associated with lower physical function, and the researchers suggest this could be due to reduced physical activity resulting in more axons being demyelinated.
A decreased myelin signal also correlated with more cognitive impairment, which is not surprising given that myelin is essential for efficient neural conduction and information processing in the brain.
The researchers also reported abnormal tissue microstructure and imbalanced neurochemicals in people with long COVID and in healthy people who had previously recovered from COVID-19.
Conclusions
This is quite a complex set of results, and there are several other results and comparisons which have not been mentioned in this summary. However, the researchers highlight a few key messages.
They have identified a number of abnormalities in the brains of people with long COVID and healthy people who have recovered from COVID-19, including altered myelin signal intensity, abnormal tissue microstructure and imbalanced neurochemicals.
In particular, there is a potential link between myelin content and symptom severity in long COVID.
These findings therefore provide evidence that COVID-19 has long-term effects on brain function.
The researchers emphasise that the relatively small number of participants and the cross-sectional nature of the study mean that the results should be interpreted with caution, and long-term follow-up studies are needed to establish whether the abnormalities progress over time.
And this is precisely what the Griffith group are doing in their ongoing ME Research UK-funded study in ME/CFS.
