Long after the last few coughs fade away, new evidence suggests that COVID-19 might still work its way through our brains.
A new multimodal MRI study suggests that people living with long COVID – along with those who appear fully recovered – show measurable changes in brain tissue, microstructure, and chemistry. Those differences might help explain persistent cognitive and physical symptoms that haunt patients long after infection.
The research, published in Brain, Behavior, & Immunity-Health, compared brain scans from three sets of patients:
- 19 people with long COVID.
- 12 individuals who’d recovered from COVID-19 without ongoing symptoms, and
- 16 healthy controls with no history of infection.
Using high-resolution MRI, the investigators examined markers of myelin, white-matter integrity, and key brain neurochemicals.
And the conclusion? SARS-CoV-2 infection appears to leave a neurological footprint that doesn’t just vanish alongside clinical recovery.
A Closer Look at the Brain’s Wiring
One of the study’s most striking findings involved changes in myelin-related signal intensity. Compared with uninfected controls, people with long COVID showed altered myelin signals in regions tied to movement and cognition, including the precentral gyrus and middle temporal gyrus.
Surprisingly, those who’d recovered from COVID-19 without long-term symptoms also showed abnormal myelin signals – particularly in the precentral gyrus and posterior cingulate cortex – suggesting that “recovery” might not mean a full neurological reset.
Diffusion tensor imaging, which tracks how water moves through brain tissue, revealed additional microstructural changes. In people with long COVID, researchers observed lower mean diffusivity in parts of the cerebellum.
At the same time, recovered participants showed lower diffusivity measures in the caudate nucleus and surrounding regions involved in motor control and learning. Earlier studies have linked similar diffusion changes to neuroinflammation and microglial activation after viral infection. And the results of this latest study raises the possibility that immune-driven processes persist long after the acute illness ends.
These white-matter differences cropped up even in individuals who no longer reported symptoms, reinforcing the idea that neurological recovery might lag behind clinical improvement.
Chemical Clues in the Brain
The study also used magnetic resonance spectroscopy to examine brain chemistry in the posterior cingulate cortex. Here, the differences that the research team noted, appeared to be more selective yet equally revealing.
Compared with recovered individuals, people with long COVID had higher levels of N-acetylaspartate (NAA). Recovered participants, on the other hand, showed higher glutamine levels.
The authors suggest these shifts might reflect altered energy use, immune activation, or compensatory metabolic responses following infection.
While the clinical implications of these neurochemical changes remain up in the air, they echo earlier reports of metabolic disruption during and after COVID-19.
Perhaps most importantly, this wasn’t purely an academic exercise. Among participants with long COVID, myelin-related signal intensity paralleled real-world symptoms. A higher myelin signal in the middle temporal gyrus aligned with better physical function. While a lower myelin signal seemed to signal worse cognitive impairment.
All told, the data point toward a biological basis for the fatigue, “brain fog,” and physical limitations that hamper so many long COVID patients.
But What Does it Mean?
The authors insist that they’re aware of the study’s limitations, based on an admittedly modest sample size and a cross-sectional study design. This, they add, offers more of a snapshot rather
than a comprehensive timeline of how these alterations progress over time.
Even so, the findings support a growing body of evidence that COVID-19 isn’t a simple respiratory illness. And its neurological effects threaten patients even after apparent recovery.
For clinicians and patients alike, the message is a sobering but enlightening one. When it comes to the brain, COVID-19’s story might not wrap up with the end of the virus itself.
Further Reading
Promising Brain-Fog Therapies Fall Flat in Long COVID Trial
