The Molecular Basis of Long Covid Brain Fog

Summary

Even though many years have passed since the start of the COVID-19 pandemic, the effects of infection with SARS-CoV-2 are not completely understood. This is especially true for Long COVID, a chronic condition that can develop after COVID-19 that causes a variety of lasting symptoms. Among the most common and debilitating of these is cognitive impairment, often referred to as “brain fog,” which affects over 80% of people with Long COVID. Given the hundreds of millions of global cases, Long COVID represents a massive public health and socioeconomic challenge, as it severely impacts people’s ability to work and perform daily activities. Unfortunately, despite its prevalence, the underlying causes of Long COVID and brain fog remain poorly understood. Previous imaging studies have shown some structural changes in the brain, but they could not pinpoint the molecular dysfunctions responsible for the cognitive symptoms. Since it’s difficult to observe the molecules that govern communication between brain cells directly, researchers are left without objective biomarkers to confirm a Long COVID diagnosis or develop therapies. To address this challenge, a research team led by Professor Takuya Takahashi from the Graduate School of Medicine at Yokohama City University, Japan, has made a significant breakthrough in understanding the cause of Long COVID brain fog. As explained in their paper, published in Brain Communications on October 01, 2025, the team hypothesized that patients with brain fog might exhibit disrupted expression of AMPA receptors (AMPARs)—key molecules for memory and learning—based on prior research into psychiatric and neurological disorders such as depression, bipolar disorder, schizophrenia, and dementia. Thus, they used a novel method called [11C]K-2 AMPAR PET imaging to directly visualize and quantify the density of AMPARs in the living human brain. By comparing imaging data from 30 patients with Long COVID to 80 healthy individuals, the researchers found a...