Even after people recover from COVID-19, their brains may retain lasting physical and chemical changes. A recent scanning study found altered brain tissue patterns and neurochemical levels in both long COVID patients and those who fully recovered, compared to individuals who were never infected. The findings were published in the journal Brain, Behavior, & Immunity – Health.
The virus responsible for COVID-19 can cause a range of persistent neurological symptoms, including brain fog, fatigue, and memory issues. While these symptoms are defining features of long COVID, some cognitive slowing also appears in people who report feeling fully recovered from the virus. Medical researchers are currently trying to map the biological roots of these brain-based symptoms. Medical imaging techniques allow experts to look inside the living brain to measure the health of its structural connections and the chemical environments that support cell function.
One target of interest is myelin, the insulating sheath that wraps around the long fibers of nerve cells. Myelin acts like the rubber coating on a copper wire, helping electrical signals travel quickly and efficiently across the brain. When myelin is damaged, communication between brain regions can slow down or fail. Another focus is the microscopic movement of water molecules through brain tissue, which can reveal subtle structural damage.
A third area of interest involves brain neurochemicals, the molecules that power brain cells and facilitate their communication. To see how these brain characteristics change after a viral infection, neuroimaging expert Kiran Thapaliya and colleagues at Griffith University in Australia designed a comparative study. The researchers set out to measure myelin levels, tissue microstructure, and neurochemical balances simultaneously. They wanted to see if distinct physical differences exist between those who never had the virus, those who fully recovered, and those still suffering from long COVID.
The research team recruited 47 adult participants for a small study. The group included 19 people with long COVID, 12 individuals who had fully recovered from a COVID-19 infection, and 16 healthy control subjects who had never contracted the virus. All participants underwent brain scanning using a powerful magnetic resonance imaging machine.
First, the team captured two types of structural images, known as T1-weighted and T2-weighted scans. By calculating the ratio between these two image types, the researchers could estimate the concentration of myelin across different regions of the brain. They also used a technique called diffusion tensor imaging to track how water molecules diffuse through brain tissue.
Normal brain tissue allows water to flow in predictable patterns, while damaged tissue alters this flow. Finally, the researchers used magnetic resonance spectroscopy to measure the concentration of specific chemical compounds in the brain.
After processing the brain scans, the researchers compared the results across the three participant groups. The myelin mapping analysis revealed altered signal intensities in both long COVID patients and fully recovered individuals when compared to the never-infected group. Specifically, people with long COVID showed elevated myelin signals in the precentral gyrus and middle temporal gyrus, brain regions involved in motor control and memory. The recovered group also showed elevated signals in the precentral gyrus and the posterior cingulate cortex compared to the uninfected control group.
When comparing long COVID patients directly to the recovered individuals, differences in myelin signals appeared in unique regions. The recovered group had higher signal intensities in the brainstem and cerebellum compared to those with long COVID. The researchers noted that these altered signals might indicate an active biological process, such as the brain attempting to repair damaged myelin sheaths or ongoing inflammation.
The water diffusion scans also pointed to lingering tissue changes. Long COVID patients displayed reduced water diffusion in certain brain regions compared to the uninfected control group. The fully recovered participants similarly showed reduced diffusion in the caudate region of the brain, an area involved in learning and memory. These altered water movement patterns suggest that the microscopic structure of the brain tissue changed following the initial viral infection.
The chemical analysis revealed imbalances primarily between the long COVID and recovered groups. The researchers found that individuals with long COVID had higher levels of N-acetyl-aspartate, a molecule related to energy metabolism in neurons. The recovered participants had higher levels of glutamine. Glutamine is an amino acid that brain cells consume for energy and immune regulation.
The team also checked to see if the brain scan measurements matched the physical and cognitive symptoms reported by the long COVID patients. They found that lower myelin signals in the middle temporal gyrus corresponded with greater physical impairment. Additionally, lower myelin signals in the midbrain correlated with worse cognitive dysfunction. This indicates that myelin health relates directly to the severity of long COVID symptoms.
The study provides an initial look at how a viral infection might leave a lasting imprint on the brain, but it has limitations. With a total of 47 participants, this is a small study, meaning the results must be interpreted cautiously until they can be replicated in a larger population. Because the researchers only scanned participants at a single point in time, the data cannot show how these brain changes develop or resolve over months or years. The findings highlight associations between brain changes and viral recovery, but they do not prove that the virus directly caused the specific myelin or chemical alterations.
Future research will need to track patients over extended periods to see if these brain changes are permanent or if they slowly revert to normal. Larger studies could also help clarify whether the elevated myelin signals represent a healthy repair process or a sign of chronic inflammation.
The study, “Altered brain tissue microstructure and neurochemical profiles in long COVID and recovered COVID-19 individuals: A multimodal MRI study,” was authored by Kiran Thapaliya, Sonya Marshall-Gradisnik, Maira Inderyas, and Leighton Barnden.