Japanese researchers identify biological cause of long COVID brain fog
Scientists in Japan have discovered a key molecular change behind the brain fog experienced by many long COVID patients. Using advanced brain imaging, they found increased density of AMPA receptors linked to cognitive impairment. The findings, published on October 1, 2025, could lead to new diagnostics and treatments.
Long COVID, a chronic condition following SARS-CoV-2 infection, affects hundreds of millions worldwide and includes debilitating symptoms like brain fog, which impacts over 80% of patients and hinders daily activities and work.
A team led by Professor Takuya Takahashi from Yokohama City University's Graduate School of Medicine addressed the unclear causes of this cognitive impairment. Previous studies showed brain structure changes but not the molecular issues. Hypothesizing disruptions in AMPA receptors—essential for memory and learning—the researchers used [11C]K-2 AMPAR PET imaging to measure receptor density in living brains.
Comparing 30 long COVID patients to 80 healthy controls, they observed widespread increases in AMPAR density across patients' brains. This elevation correlated directly with the severity of cognitive symptoms and levels of inflammatory markers, suggesting inflammation's role.
The imaging method distinguished patients from controls with 100% sensitivity and 91% specificity, offering a potential biomarker. "By applying our newly developed AMPA receptor PET imaging technology, we aim to provide a novel perspective and innovative solutions to the pressing medical challenge that is Long COVID," Prof. Takahashi remarked.
These results confirm brain fog as a measurable biological condition, targeting AMPAR suppression for therapies. "Our findings clearly demonstrate that Long COVID brain fog should be recognized as a legitimate clinical condition. This could encourage the healthcare industry to accelerate the development of diagnostic and therapeutic approaches for this disorder," Prof. Takahashi concluded.
The study, published in Brain Communications (DOI: 10.1093/braincomms/fcaf337), was supported by sources including the Japan Agency for Medical Research and Development.