Long COVID brain fog affects work, school, and daily life. A new human study shows a clear biological sign: higher levels of AMPA receptors, the brain’s fast “on” switches for learning and memory. Using a PET scan tracer named K‑2, researchers saw these receptors were elevated across many brain areas in people with long COVID who had thinking problems. The amount of increase tracked with worse test scores and higher inflammation in blood.
Long COVID brain fog and AMPA receptors
In the new study, scientists used a specialized PET scan called [11C]K‑2 to visualize AMPA receptors (AMPARs), which are proteins that let the signal chemical glutamate excite nerve cells. The authors report that elevated AMPAR density separated the long COVID group from healthy people with 100% sensitivity and 91% specificity. They also found that higher AMPAR levels were linked to worse memory and attention scores, and to inflammatory markers in blood.
What AMPARs do, in simple terms
AMPARs sit on the receiving side of synapses. They are key to forming and changing connections when we learn. The K‑2 tracer binds to receptors on the cell surface, which means the scan reflects active synapses rather than stored receptors inside the cell. Prior work confirms that K‑2 PET images the cell-surface fraction of AMPARs in living humans.
How the scan was done
The team scanned 30 people with long COVID cognitive symptoms and 80 healthy volunteers. They compared the strength of the K‑2 signal in many brain regions. The long COVID group showed widespread increases. A machine‑learning model based on these images separated the two groups with high accuracy. In plain language, the scan could tell who had long COVID brain fog with strong confidence.
Related reading: taking strategic breaks every 90 minutes can help protect focus during the day. See our guide on taking strategic breaks every 90 minutes keeps the brain sharp.
PET scans show AMPA receptor increase
The method uses a short‑lived carbon tracer, so it currently requires a cyclotron on site. The same group is developing a fluorine tracer with a longer half‑life, which could make the test easier to share across hospitals. The university notes that higher AMPAR density tracked closely with symptom severity, suggesting a measurable biomarker and a drug target. For now, this is a research tool, not a clinic test.
Also see: how sound rhythms can nudge brain state in some people. Read about listening to theta binaural beats may help calm and sleep.
What this could mean for diagnosis and treatment
If confirmed by larger studies, AMPAR PET could help doctors confirm brain‑fog cases that are hard to diagnose. The authors also suggest testing AMPAR blockers as treatments. One example is perampanel, a non‑competitive AMPAR antagonist already used for epilepsy. The paper proposes that AMPAR antagonists might reduce excessive excitatory signaling seen in long COVID. This idea needs randomized trials before any clinical use.
Related: the brain can reshape how it feels the body and pain under certain conditions. See our overview on virtual avatars rewire body perception and ease trauma through brain plasticity.
Limitations and quality of evidence
- Evidence type: human imaging study with machine‑learning classification; not a treatment trial.
- Sample: 30 patients with long COVID cognitive symptoms, 80 healthy controls.
- Bias and conflicts: Funding included public grants and crowdfunding. The lead researcher holds a patent related to the AMPAR tracer and co‑founded a company that licenses it; see the paper’s declared funding and competing interests. This makes independent replication essential.
- Generalization: The results come from one center in Japan. People with different clinical histories may vary. We need multi‑site cohorts and blinded external validation.
Brain Communications – Systemic increase of AMPA receptors associated with cognitive impairment of long COVID – 2025
The authors report that elevated AMPAR density distinguished long COVID cases from controls with 100% sensitivity and 91% specificity. Evidence type: human PET imaging; exploratory diagnostic model; conflicts and funding disclosed.
Yokohama City University – Uncovering the molecular basis of long COVID brain fog – 2025
The university press note explains that higher AMPAR density tracked symptom severity and inflammatory markers, suggesting a biomarker and a therapeutic target.
PubMed – [11C]K‑2 image with positron emission tomography depicts cell‑surface AMPARs – 2021
Earlier validation shows that the K‑2 tracer reflects cell‑surface AMPARs that matter for synaptic signaling. Evidence type: human tracer study.
AuntMinnie – PET reveals mechanism underlying brain fog in long COVID – 2025
A radiology outlet summarizes that brain regions with higher K‑2 signal were tied to poorer memory and naming performance, and to inflammation in the study.
News-Medical – New study reveals molecular basis of long COVID brain fog – 2025
A science news site reports that K‑2 AMPAR PET visualized and quantified receptor density in living human brain, aligning with the primary paper’s findings.
0 Comments