Nikhil Prasad Fact checked by:Thailand Medical News Team Jun 25, 2026 1 hour, 21 minutes ago
Medical News: For many people, recovering from COVID-19 does not mean the illness is truly over. Months after the infection has cleared, many continue to struggle with memory problems, difficulty concentrating, slower thinking, and trouble planning or making decisions. These symptoms, commonly known as "brain fog," have become one of the most disabling features of long COVID. Now, researchers have identified tiny molecules circulating in the bloodstream that could help explain why some people develop these lingering cognitive problems while others recover without them.
Scientists identify unique blood microRNA signatures that could help detect and explain cognitive impairment in people
with long COVID
Scientists from the Universitat de Girona, the Consorci Sanitari de Terrassa, the Universitat de Barcelona, the Universitat Internacional de Catalunya, and Catlab, all in Spain, have discovered that specific blood microRNAs are closely linked to cognitive impairment in people with post-COVID condition. Their findings suggest these molecules could eventually become simple blood biomarkers to identify patients at risk of long-term neurological complications.
Understanding Long COVID Brain Fog
Post-COVID condition, often called long COVID, refers to symptoms that continue or appear at least three months after the initial SARS-CoV-2 infection and last for at least two months without another medical explanation. While fatigue remains the most common complaint, many patients also experience cognitive difficulties that interfere with work, daily activities, and quality of life.
Previous studies have estimated that between 7.2 percent and 59.2 percent of COVID-19 survivors develop measurable cognitive dysfunction. The most commonly affected abilities include memory, attention, mental processing speed, and executive function, which involves planning, problem-solving, multitasking, and decision-making. In some individuals, these problems may persist for several years.
Tiny Molecules That Control Brain Function
MicroRNAs are very small RNA molecules that help regulate the activity of thousands of genes throughout the body. They play critical roles in brain development, nerve cell communication, learning, memory formation, inflammation, and repair of damaged tissues.
Because microRNAs remain remarkably stable in blood plasma, scientists have increasingly investigated them as non-invasive biomarkers for neurological disorders such as Alzheimer's disease and mild cognitive impairment. However, little was previously known about whether they also play a role in long COVID-related brain dysfunction.
To answer this question, the Spanish research team analyzed blood samples from 64 participants, including 48 individuals with post-COVID condition and 16 healthy volunteers. Every participant underwent an extensive series of neuropsychological tests evaluating memory, attention, processing speed, executive function, and overall cognitive performance before their blood samples were analyzed.
Researchers Identify a Distinct Blood Signature
The researchers examined an impressive panel
of 754 human microRNAs and detected 478 circulating in blood plasma. After comparing cognitively impaired long COVID patients with cognitively healthy long COVID patients, they identified 13 microRNAs that showed significant differences in expression.
Many of these altered microRNAs regulate biological pathways that are already known to be involved in brain aging and neurodegenerative diseases. These pathways include the FoxO signaling pathway, Hippo signaling pathway, neurotrophin signaling pathway, axon guidance, and mechanisms involved in maintaining healthy nerve cell connections and brain plasticity. Their disruption could help explain why some patients continue experiencing persistent cognitive symptoms long after the original infection has resolved.
As highlighted in this
Medical News report, these biological findings provide growing evidence that long COVID brain fog is associated with measurable molecular changes rather than simply subjective complaints.
Four MicroRNAs Stand Out
The investigators then validated four of the most promising microRNAs in a larger group of participants.
Patients with cognitive impairment consistently showed significantly lower levels of miR-448, miR-450a, and miR-483, while miR-369 was present at higher levels compared to healthy controls.
Among these, miR-448 and miR-450a emerged as the strongest indicators of cognitive impairment. Their reduced levels remained significant even after accounting for age, sex, and educational background.
The researchers also found that these microRNAs closely reflected actual cognitive performance. Higher miR-448 levels were associated with stronger verbal memory and language-related executive function. Increased miR-450a levels correlated with better overall cognitive scores, faster processing speed, and improved attention. Higher miR-483 levels were linked to better mental flexibility and quicker task completion.
These consistent relationships suggest the blood microRNAs are directly associated with the brain functions affected in long COVID.
Blood Test Shows Promise
Perhaps the most exciting finding was that combining miR-448 and miR-450a produced a blood signature capable of distinguishing cognitively impaired long COVID patients from cognitively healthy patients with good diagnostic accuracy. The combined marker achieved approximately 80 percent sensitivity and 71 percent specificity, indicating strong potential as a future clinical screening tool.
Although additional research involving much larger patient populations is needed before such testing becomes available in hospitals, these findings represent an important step toward developing objective laboratory tests for long COVID brain fog.
Important Step Toward Better Diagnosis
The researchers acknowledge that their study was exploratory and involved a relatively modest number of participants. Nevertheless, the findings provide compelling evidence that persistent cognitive impairment after COVID-19 is associated with distinct biological changes that can be detected through a simple blood sample. Larger longitudinal studies will now be needed to confirm these biomarkers and determine whether they can also predict disease progression or monitor recovery over time. If validated, these microRNAs could help clinicians diagnose cognitive impairment earlier, better understand the biological mechanisms driving long COVID, and eventually develop targeted therapies that improve neurological recovery for millions of affected individuals worldwide.
The study findings were published in the peer reviewed journal: Scientific Reports.
https://www.nature.com/articles/s41598-026-56848-0
For the latest on Long COVID, keep on logging to Thailand
Medical News.
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