“Brain Fog” in Long-Covid: Oxford University Finds Possible Causes

Inflammatory markers CRP and blood clotting factor I lead to measurable cognitive impairment

According to epidemiological studies, approximately 36 million people in the WHO Europe region alone are thought to have developed Long Covid symptoms in the past three years, with cognitive impairment being common. Currently, it is estimated that up to 32 percent of those affected suffer from “brain fog” as a post-acute consequence of SARS-CoV-2 infection. However, the underlying biological causes are as yet unknown. Scientists at Oxford University have now identified two possible causes, which have been published in the journal NATURE MEDICINE.

In a prospective cohort study of 1,837 adult patient:s hospitalized for COVID-19, the researchers identified two distinct biomarker profiles measured during the acute admission that allowed predictions of cognitive function at six and 12 months after COVID-19.

Probably one in eight affected by cognitive deficits

In their study, first author Maxime Taquet and his colleagues from the Department of Psychiatry at the University of Oxford report that approximately one in eight patients affected by COVID-19 are diagnosed with neurologic or psychiatric symptoms within six months of acute infection. Of particular concern are cognitive deficits, including so-called “brain fog.” These occur frequently and can persist over a prolonged period of time, the author:s noted.

Elevated levels of fibrinogen and D-dimer detected

The researcher:s identified two main markers: The first marker was an elevated level of the protein fibrinogen, while the second marker indicated an elevated level of the protein fragment D-dimer. Other aspects of the biomarker profiles suggested that they were likely related to blood clot formation. The main findings were verified by analyzing more than 90 million U.K. electronic medical records.

During analysis and subsequent follow-up, the researchers found the following relationships: patients who had elevated levels of blood clotting factor I (fibrinogen) compared with the inflammatory marker CRP (c-reactive protein) during their acute COVID-19 illness were more likely to subsequently experience objectively measurable cognitive impairment. Fibrinogen is a protein produced in the liver. Elevated levels of this protein in the blood also indicate inflammatory processes that can simultaneously activate blood clotting.

Fibrinogen can cause direct damage to nerve cells in the brain

Subjects with elevated fibrinogen levels also performed significantly worse in a test that assessed subjectively perceived cognitive problems. This could possibly be related to the formation of microthrombi in the brain. Fibrinogen is also known to cause direct damage to neurons in the brain.

D-dimer indicates thrombus formation in small blood vessels

The second marker, D-dimer, is a classic marker for thrombosis. The British scientists:in this case also discovered a clear link between elevated D-dimer levels and cognitive impairment.

One possible explanation could be that elevated D-dimer levels in the blood of COVID-19 indicate the formation of thrombi in the small blood vessels of the lungs. This, in turn, could lead to a long-term reduction in oxygen uptake and trigger fatigue states.

Significant advance in understanding the causes of Long Covid symptomatology

Dr. Taquet concluded, “Both fibrinogen and D-dimer are involved in blood clotting, and thus the results support the hypothesis that blood clots are a cause of cognitive problems after COVID. Fibrinogen may act directly on the brain and its blood vessels, while D-dimer often reflects blood clots in the lungs, and the problems in the brain may be due to lack of oxygen. Consistent with this possibility, people who had high levels of D-dimer were not only at higher risk for brain fog, but also at higher risk for respiratory problems.”

The ultimate goal now, he said, is to prevent and reverse the cognitive problems that occur in many people after COVID-19 infection. Although the findings represented a significant advance in understanding the causes of these symptoms, further research into the causes and effects is needed before possible interventions can be proposed and tested, Maxime Taquet said in a statement.

The full article, titled “Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization ” can be read in NATURE MAGAZINE: