Brain Fog in Long COVID Linked to Increase in AMPA Receptors

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While the COVID pandemic has thankfully been over for some time now, there is still a considerable number of people in the world (about 400 million) suffering from long COVID. Long COVID is a chronic condition that can affect people who, at one time, had an acute COVID infection. Long COVID can persist for years, and unlike an acute COVID infection that mostly affects the lungs, it can also affect brain function. While the symptoms of long COVID can be very diverse, more than 80 percent of patients with long COVID suffer from so-called brain fog. Brain fog is a colloquial term used to describe impairments in various brain functions, such as memory, decision-making, and reasoning. In heavily affected long COVID patients, brain fog can be so bad that they may be unable to work their normal jobs. Brain fog is difficult to treat, and one major problem is that scientists so far really have not understood very well which biological factors cause brain fog.

A new study on brain fog in long COVID

A new study published October 1^st, 2025, in the scientific journal Brain Communications now sheds light on molecular changes in brain synapses associated with long COVID (Fujimoto and co-workers, 2025). In the study entitled “Systemic increase of AMPA receptors associated with cognitive impairment of long COVID”, the scientists used a special form of positron emission tomography (PET) to visualize the density of so-called AMPA receptors in the brains of 30 long COVID patients and 80 healthy volunteers. AMPA is short for alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. AMPA receptors are an important class of receptors for the neurotransmitter glutamate in the brain. It is very important for the fast transmission of neuronal information in the brain and plays a crucial role in learning and memory. As such, AMPA receptors are likely relevant for brain fog in long COVID that affects these brain functions.

AMPA receptor density is a promising biomarker for brain fog in long COVID

The scientists made an extremely interesting finding: A statistical analysis across the whole brain revealed that the AMPA receptor density in long COVID patients was significantly higher than in healthy people. Similar results were also found for several individual brain areas. Even more interestingly, an increase in AMPA receptors in several brain areas was associated with worse performance in neuropsychological memory recall and reasoning tests. Moreover, additional analyses revealed that an increase in AMPA receptors was also linked to an increase in several immune system activity markers, sometimes very strongly.

Takeaway

The results of the study showed that an increase in AMPA receptors in long COVID patients was linked to more brain fog, as reflected by the worse performance in the cognitive tests. The scientists discussed that too many of these receptors relevant for information processing in the brain may mess up cognitive processing, explaining why brain fog occurs. In addition, due to the link between AMPA receptor increase and massive changes in immune system activity, the scientists suggested that excessive brain activity due to too many AMPA receptors may have neurotoxic effects on the brain. Therefore, targeting AMPA receptors in the therapy of long COVID may be a very promising approach to help these often severely impacted patients.