Nikhil Prasad Fact checked by:Thailand Medical News Team Jun 12, 2025 3 weeks, 5 days, 6 hours, 7 minutes ago
Thailand Medical News: In a groundbreaking new study, scientists have uncovered unique genetic fingerprints that could explain why some people continue to suffer from persistent brain fog after recovering from COVID-19. These findings not only shed light on the biological underpinnings of long COVID-related cognitive issues but also reveal surprising links between the brain, heart, and blood vessels.
Long COVID Brain Fog Tied to Dangerous Vascular and Heart Related Gene Changes
The research was conducted by a team from the S. N. Pradhan Centre for Neurosciences at the University of Calcutta in India, along with collaborators from OmicsLogic Inc. in Houston, Texas, and OmicsLogic Bioinformatics & Data Science in New Delhi, India. This
Thailand Medical News report highlights their discovery of distinct transcriptomic biomarkers—unique gene expression patterns in blood—that are specifically associated with long COVID patients suffering from brain fog.
Brain Fog Is More Than Just Mental Fatigue
Brain fog, a term commonly used by patients to describe mental confusion, forgetfulness, and trouble concentrating, has emerged as one of the most frustrating symptoms of long COVID. While previous research focused mainly on inflammation and blood-brain barrier damage, this study goes a step further by identifying genes and molecular pathways that link the brain to heart and vascular health.
Using advanced RNA sequencing data from peripheral blood samples, researchers compared four groups: healthy individuals, recovered COVID-19 patients, long COVID patients without brain fog, and those suffering from long COVID with brain fog. This comparative analysis revealed that patients with brain fog had a unique and distinct gene expression signature, especially involving genes associated with cardiovascular and neurovascular function.
Key Genes Behind Brain Fog Revealed
Several genes were found to be either significantly overactive or underactive in patients with brain fog. For instance:
-
EDNRB (Endothelin Receptor Type B): Highly overexpressed, this gene is linked to blood vessel function and brain blood flow. Its activation could contribute to inflammation and impaired brain perfusion.
-GRIN2C: A subunit of the NMDA receptor, essential for memory and learning. Altered expression of this gene may lead to disruptions in synaptic communication and brain plasticity.
-NOS2 (inducible nitric oxide synthase): Involved in producing nitric oxide, a molecule that in excess can become toxic to brain cells and promote inflammation.
-NRCAM and DHRS9: Genes involved in immune response and maintaining blood-brain barrier integrity, both found to be significantly downregulated.
These genes collectively suggest that long COVID brain fog could be the result of a harmful combination of inflammation, vascula
r dysfunction, and neurotransmitter disruption.
Involvement of Heart and Blood Vessel Pathways
KEGG pathway analysis (a tool used to identify biological mechanisms) showed that patients with brain fog had overactive pathways linked to:
-Dilated and hypertrophic cardiomyopathy (heart muscle disease)
-Relaxin signaling (a hormone-related pathway known to regulate blood vessel tone and reduce inflammation)
-Calcium signaling, which is crucial for nerve signal transmission and heart muscle contraction
Notably, the relaxin pathway emerged as a potentially protective mechanism, possibly attempting to counterbalance the damaging effects of other activated pathways.
What This Means for Long COVID Patients
These findings highlight that brain fog is not just a symptom of neurological damage but is deeply intertwined with cardiovascular and immune system dysfunction. The overexpression of EDNRB and NOS2 implies an environment of chronic vascular stress and inflammation in the brain, while the underactivity of genes like NRCAM hints at a weakened blood-brain barrier—allowing more harmful substances to enter brain tissue.
This research suggests that monitoring these biomarkers in blood could one day help diagnose or even predict brain fog in long COVID sufferers. It also opens the door to potential treatments that target cardiovascular health to alleviate cognitive symptoms. For example, drugs that enhance relaxin signaling or modulate nitric oxide levels might provide relief by restoring blood vessel health and reducing oxidative stress in the brain.
Conclusion
This new study offers crucial insights into why brain fog persists in many long COVID patients. By pinpointing genes that control heart, blood vessel, and brain function, researchers have revealed that brain fog is far more complex than previously thought. It is not just a lingering symptom but a distinct biological condition tied to cardiovascular and neurovascular abnormalities. These findings not only pave the way for new diagnostic tools but also offer hope for targeted therapies that could relieve brain fog by treating the root causes hidden in the blood. As the medical community continues to grapple with the long-term effects of COVID-19, such research is essential in crafting a comprehensive approach to patient care.
The study findings were published on a preprint server and are currently being peer reviewed.
https://www.biorxiv.org/content/10.1101/2025.06.10.656785v1
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https://www.thailandmedical.news/news/sars-cov-2-nsp1-protein-stalls-human-dna-replication-contributing-to-dangerous-long-term-health-issues
https://www.thailandmedical.news/news/american-study-alarmingly-finds-that-non-hospitalized-long-covid-patients-show-reduced-retinal-blood-flow
https://www.thailandmedical.news/news/malaysian-researchers-find-that-long-covid-individuals-are-likely-to-have-executive-function-deficits-and-altered-brains
https://www.thailandmedical.news/articles/long-covid
https://www.thailandmedical.news/articles/coronavirus
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