The most profound effects of COVID-19 might not be in our lungs, but in our brains.
Imagine surviving a respiratory infection only to find your own mind has become unfamiliar.
Simple words escape you, fatigue becomes a constant companion, and the world's smells and tastes have faded into a bland uniformity. This is the reality for millions living with Long COVID neurological complications 7 .
Once dismissed as mere psychological fallout, researchers have now uncovered tangible biological evidence that SARS-CoV-2, the virus behind COVID-19, exerts powerful effects on our nervous system. From altering the brain's very structure to rewiring its cellular communication, the virus leaves a mark that science is just beginning to decipher 5 1 .
SARS-CoV-2 might enter through the nose and mouth, but its reach extends far beyond the respiratory system. Researchers have identified several pathways through which it can impact brain function and structure.
The virus gains entry to human cells by latching onto ACE2 receptors, proteins found throughout the body, including in the neural tissue of the brain 8 . Some studies have detected viral particles in the brains of deceased COVID-19 patients, suggesting the virus can indeed cross protective barriers 8 .
Many experts now believe the primary driver of neurological symptoms is the body's own inflammatory response to the virus 2 . This "cytokine storm" can damage the blood-brain barrier, allowing inflammatory substances to reach sensitive neural tissue and disrupt normal function 2 3 .
COVID-19 triggers remarkable changes in our blood vessels. Hematologists have observed that it's not just about classic blood clots. The virus causes endothelial cell damage (damage to the lining of blood vessels) throughout the body and brain 8 .
Furthermore, immune cells called neutrophils release sticky "neutrophil extracellular traps" (NETs) – spider-web-like structures meant to ensnare pathogens. In COVID-19, these NETs can persist, clogging tiny blood vessels in the brain and cutting off oxygen to neural cells 7 .
When neurological symptoms linger beyond three months, patients enter the complex realm of Long COVID or Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) 6 . The scope is staggering: a 2025 meta-analysis of over 4 million patients found that 43.3% of COVID-19 survivors experienced persistent fatigue, while over a quarter reported memory disorders (27.8%) and cognitive impairment (27.1%) 9 .
Among Long COVID's mysteries, "brain fog" has been particularly elusive – until recently. In October 2025, a Japanese research team published a groundbreaking study that finally provided a biological explanation for this debilitating symptom 1 .
Professor Takuya Takahashi's team at Yokohama City University employed an innovative approach to visualize what previous imaging techniques could not detect 1 :
The researchers used a novel technique called [11C]K-2 AMPAR PET imaging to directly visualize and quantify the density of AMPA receptors in the living human brain. These receptors are crucial for memory formation and learning 1 .
They compared brain scans from 30 patients with Long COVID to 80 healthy individuals, creating a clear experimental contrast 1 .
The team then analyzed whether changes in AMPA receptor density correlated with the severity of patients' cognitive symptoms and levels of inflammatory markers 1 .
The findings, published in Brain Communications, revealed striking differences:
100%
Sensitivity
91%
Specificity
"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."
Perhaps the most startling neurological discovery emerged from analysis of the UK Biobank, which compared brain scans from before and after the pandemic's onset 5 .
The research revealed that the pandemic itself – regardless of SARS-CoV-2 infection – was associated with accelerated brain ageing. Using machine learning models trained on pre-pandemic scans, scientists found that brains aged approximately 5.5 months faster than expected during the pandemic period 5 .
This effect was more pronounced in males and those from deprived socio-demographic backgrounds. However, the crucial distinction was that accelerated brain ageing correlated with reduced cognitive performance only in those who had been infected with COVID-19 5 .
Pandemic Group
(No Infection)
Pandemic Group
(With COVID-19)
Pre-Pandemic
Controls
Brain aging acceleration measured in months beyond expected trajectory
Accelerated by ~5.5 months with no significant cognitive correlation. More pronounced in males and deprived backgrounds.
Accelerated by ~5.5 months and correlated with reduced cognitive performance. Infection status drives cognitive impact.
Normal ageing trajectory with normal cognitive correlation.
The research breakthroughs in understanding COVID-19's neurological effects rely on sophisticated tools and techniques.
This specialized imaging technique uses radioactive tracers to visualize and quantify AMPA receptors in living brains, revealing the molecular underpinnings of conditions like brain fog 1 .
These machine learning algorithms analyze hundreds of brain imaging features to estimate a person's "brain age," which can be compared to their chronological age to detect accelerated ageing 5 .
Researchers use specialized staining and microscopy techniques to detect and measure neutrophil extracellular traps (NETs) that can clog blood vessels in the brain 7 .
Large, longitudinal collections of health and imaging data from hundreds of thousands of participants enable powerful comparisons between pre-pandemic and pandemic-period brain health 5 .
The neurological manifestations of COVID-19 represent more than scientific curiosities – they translate to real-world limitations. As one specialist noted, "There's no confirmatory test, no single fix, and no specialty that fully owns this condition. It's deeply frustrating for both patients and providers" 7 .
Multidisciplinary clinics, like Stanford's Post-Acute COVID-19 Syndrome Center, have emerged to address this complexity, bringing together neurologists, ENT specialists, hematologists, and psychiatrists to tackle the multi-system nature of Long COVID 7 .
Neurologists
ENT Specialists
Hematologists
Psychiatrists
Multidisciplinary approach to Long COVID treatment
Research initiatives such as the NeuroCOVID Project – a national databank-biobank collaboration funded by the National Institutes of Health – are creating vital research infrastructure to support future discoveries 4 .
The journey to understand COVID-19's impact on the brain has revealed a complex picture of a virus that exerts its effects through multiple pathways: direct invasion in some cases, inflammatory storms, vascular damage, and profound receptor changes.
What began as reports of "brain fog" and lost smells has evolved into a sophisticated understanding of AMPA receptor disruptions and accelerated brain aging. The discoveries of tangible biological correlates for these symptoms validate patients' experiences and pave the way for targeted treatments.
As research continues to untangle these complex mechanisms, each discovery brings us closer to effective diagnostics and interventions. The work represents not just a response to the current pandemic, but an investment in understanding brain health that may benefit countless individuals facing neurological challenges in the future.
This article synthesizes findings from recent peer-reviewed studies and clinical reports to provide a comprehensive overview of the current understanding of COVID-19's neurobiological impacts.