Playing with your children or meeting a friend for coffee are everyday activities that many people move between without giving much thought to how much mental or physical energy they take.
For many people living with long COVID, things are different. Reading, working at a computer or concentrating on a conversation can require far more effort than it once did, and mental fatigue can make it difficult to keep going.
Fatigue is one of the most common symptoms of long COVID, also known as post-COVID condition. For some people it improves over time. For others it can persist for months or years, interfering with work, family life and social activities.
Scientists are still trying to understand what drives this exhaustion. Research has pointed to several possible biological processes, including changes in the immune system and nervous system. No single explanation has emerged, and different mechanisms may contribute in different people.
Our new study offers another clue. We found lower blood flow in the brains of people with long COVID who experienced persistent fatigue. These differences were also related to aspects of fatigue and performance on a task requiring sustained attention.
To investigate this, my colleagues and I studied 22 people with long COVID who continued to experience fatigue, comparing them with 19 healthy volunteers matched for age and sex.
Participants completed a 20-minute task requiring them to stay alert and respond quickly to visual signals. While they did this, we measured blood flow in their brains using a specialised form of MRI called arterial spin labelling. The technique uses the water already present in blood as a natural marker, allowing researchers to estimate how much blood reaches different parts of the brain without injecting a contrast agent.
We also asked participants to rate their fatigue before and after the task.
A clear pattern emerged. People with long COVID felt more fatigued before the task and reported a greater increase in fatigue afterwards. They also responded more slowly throughout the attention test than the healthy volunteers.
However, their performance did not worsen significantly more as the task went on. This distinction is important because feeling increasingly fatigued is different from showing a measurable decline in performance over time.
The brain scans revealed lower overall cerebral blood flow, meaning the amount of blood reaching the brain, in the long-COVID group. Larger differences appeared in several regions involved in processes including attention, sensory processing and cognitive control.
Lower blood flow was also associated with slower reaction times. These findings suggest that changes in cerebral blood flow may be one part of the biological picture behind fatigue and concentration difficulties in long COVID.
The finding fits with other neuroimaging research. Previous studies have also reported differences in brain blood flow or oxygen metabolism in people with post-COVID conditions, although findings vary and researchers have yet to establish exactly how these changes relate to symptoms.
There are important limitations. Our study was small, so the results need to be tested in much larger groups. It also shows associations rather than cause and effect. We cannot tell whether lower cerebral blood flow contributes to fatigue, results from another underlying process, or accompanies it for another reason.
The MRI method also has limits. It cannot fully distinguish between reduced blood flow within brain tissue and changes in how blood moves through the brain’s small blood vessels.
Long COVID itself is complex. Research suggests it can involve several body systems and biological processes, and the balance may differ from person to person. The brain blood-flow differences found in our study therefore cannot provide a single explanation for everyone’s fatigue.
This type of brain scan also cannot currently diagnose long-COVID fatigue in an individual patient. Routine clinical tests may still fail to capture biological changes associated with symptoms that have a major effect on someone’s daily life.
What the study provides is another piece of evidence that persistent fatigue after COVID can be associated with measurable physiological differences. Understanding whether changes in cerebral blood flow contribute directly to symptoms, and whether they could eventually help guide treatment, will require larger studies following people over time.
Sonia Miri Hedberg receives funding from Promobilia
