Checking your calendar, sorting through a few decisions, or trying to follow a complicated set of instructions can seem like small tasks. Usually, the brain handles them without demanding much attention in return.
For some people living with long COVID, that mental effort can feel surprisingly expensive. Tasks that once seemed routine can leave them feeling drained, even when they have barely moved. CDC data from 2023 estimated that about 9.2 million U.S. adults were living with long COVID, with 6.4% of adults reporting the condition when surveyed. Nearly 1 in 5 adults with long COVID reported significant activity limitations because of their symptoms.
A small Swedish study may now offer a clue about what is happening inside the brain. Researchers found that people with long-COVID fatigue had slightly lower cerebral blood flow and slower, more variable responses during a 20-minute attention test.
The finding does not explain every case of long COVID. But it gives researchers something physical to investigate.
The study put long-COVID fatigue under a microscope
Researchers at Danderyd Hospital’s Cognitive Post-COVID Outpatient Clinic, together with Karolinska Institutet and Karolinska University Hospital, compared 22 people with long-COVID fatigue with 19 healthy volunteers.
The participants completed a 20-minute sustained-attention test while researchers assessed their performance and brain activity. Brain imaging was also used to examine cerebral blood flow.
The long-COVID group had slightly lower average blood flow in the brain, with more noticeable differences in several regions involved in attention, sensory processing, and cognitive control.
Their responses were also slower and more variable.
That variability matters. The participants were not simply slow on every response. Their reaction times fluctuated more, suggesting that maintaining a consistent level of attention may have been more difficult.
They felt more exhausted, but their performance did not collapse
One of the study’s more interesting findings is what did not happen.
Participants with long COVID reported becoming more fatigued during the 20-minute task. Yet their performance did not deteriorate significantly more than the healthy volunteers’ performance as the test continued.
That creates an important distinction between feeling mentally exhausted and showing a measurable decline in performance.
The study therefore does not support a claim that people with long COVID simply lose the ability to concentrate after a certain amount of time. Instead, the participants were slower overall and showed greater variability in their responses while also reporting more fatigue.
That difference is important because the researchers were measuring a very specific laboratory task, not everyday activities such as working, driving, or caring for children.
Why brain blood flow could matter
The Swedish findings are particularly interesting because they add to previous research examining circulation in people with persistent symptoms after COVID-19.
A 2021 study looked at 10 people with long COVID during a head-up tilt test. All 10 developed postural orthostatic tachycardia syndrome, or POTS, during the test. Researchers also found larger reductions in cerebral blood flow and cardiac index among the patient group than among healthy controls.
The sample was tiny, so it cannot establish that POTS or reduced brain blood flow explains long-COVID fatigue for everyone.
But it raises another possibility: for some people, symptoms may be connected to how effectively the body maintains circulation to the brain, particularly when a person is upright.
Related: 10 Simple Habits to Recharge Your Mind and Body
Brain fog may involve the blood-brain barrier, too
Another line of research has focused on something different: the blood-brain barrier, the system that regulates what passes between the bloodstream and brain tissue.
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In a 2024 Nature Neuroscience study, researchers compared 32 people across three groups: 10 who had recovered from COVID-19, 11 people with long COVID but no brain fog, and 11 people with long COVID and brain fog.
Using specialized dynamic contrast-enhanced MRI, researchers found greater blood-brain-barrier permeability in participants with brain fog, including changes in the frontal cortex and temporal lobes.
The researchers also identified inflammatory and vascular-related changes.
That does not mean researchers have proven that long COVID causes a permanently “leaky brain.” The study was small, and it could not establish whether changes in the blood-brain barrier cause brain fog, result from it, or occur alongside it.
The fatigue may not be coming from the brain alone
Long-COVID fatigue has also been investigated at the muscle level.
A 2024 study published in Nature Communications examined 25 people with long COVID who experienced post-exertional malaise and compared them with 21 people who had recovered from mild COVID-19.
After a maximal cycling test, the long-COVID group showed lower peak oxygen uptake, lower peak power output, and reduced peripheral oxygen extraction. Researchers also found lower skeletal-muscle oxidative-phosphorylation capacity and a higher proportion of easily fatigued glycolytic muscle fibers.
Some muscle abnormalities became more pronounced after exercise. Symptoms including fatigue, muscle pain, and cognitive problems could persist for up to seven days after the test.
The researchers did not find evidence that amyloid deposits were blocking muscle capillaries and causing local oxygen starvation, which is important because it ruled against one proposed explanation for the muscle findings.
The study still cannot prove that these muscle changes cause post-exertional malaise. It does, however, show measurable physiological differences in a carefully selected group of patients whose symptoms worsened after exertion.
What the new study does and does not show
The Swedish research adds another piece to a growing collection of findings involving the brain, circulation and muscles.
But these studies should not be treated as evidence that researchers have identified one cause of long COVID.
The new study involved just 41 participants. The tilt-table research involved 10 people with long COVID. The blood-brain-barrier study also used very small groups, and the muscle research focused specifically on patients with post-exertional malaise.
These are clues, not a finished explanation.
The Swedish researchers found a relationship between lower cerebral blood flow, attention performance, and fatigue. They did not establish that reduced blood flow causes fatigue, nor that changing blood flow would relieve symptoms.
For now, the value of the research is that it moves the conversation beyond simply asking whether people with long COVID feel exhausted. Researchers are finding measurable differences that may eventually help explain why that exhaustion can be so difficult to shake.
Do you think we still underestimate how much long COVID can affect everyday life?
