COVID-19 Blood Clots Could Be Causing Brain Fog

Researchers have identified two proteins that could be used to identify those at risk of developing cognitive issues, such as brain fog, post-infection with COVID-19. The findings also indicate that blood clots may be to blame.

Long COVID is thought to affect between 10 to 20 percent of those infected with SARS-CoV-2, with people experiencing symptoms such as fatigue, difficulty breathing, and cognitive impairment for months or even years after infection. One of the most commonly reported of these issues is “brain fog”, during which people encounter problems with thinking, concentration, and memory.

A new study sought to find proteins associated with brain fog that could therefore be used as biomarkers. Researchers used data from participants in the UK-based PHOSP-COVID study, including the blood tests of 1,837 people who had been hospitalized with COVID between January 29, 2020, and November 20, 2021. 

They compared this information with the results of cognitive assessments performed both by clinicians and by patient self-reporting. Taken six and 12 months after hospitalization, the assessments measured abilities such as executive function, memory recall, and attention.

Using statistical analysis, two different potential biomarkers were identified — high levels of the protein fibrinogen and an increased level of D-dimer, a protein fragment. Both molecules are involved in blood clotting, which gave researchers a clue as to a possible cause of COVID-associated brain fog.

“Both fibrinogen and D-dimer are involved in blood clotting, and so the results support the hypothesis that blood clots are a cause of post-COVID cognitive problems,” said study author Dr Maxime Taquet in a statement.

The findings were also replicated using data from the electronic healthcare records of patients in the US.

As for how clotting related to these proteins could lead to brain fog, Taquet explained:

“Fibrinogen may be directly acting on the brain and its blood vessels, whereas D-dimer often reflects blood clots in the lungs and the problems in the brain might be due to lack of oxygen. In line with this possibility, people who had high levels of D-dimer were not only at a higher risk of brain fog, but also at a higher risk of respiratory problems.”

Though the researchers hope that the study’s results provide a solid basis for understanding the mechanisms behind post-COVID brain fog, there’s recognition that it will take time for there to be a clinical impact. 

“The ultimate goal is to be able to prevent and reverse the cognitive problems seen in some people after COVID-19 infection. Although our results are a significant advance in understanding the basis of these symptoms, more research is needed into the causes and effects before we propose and test interventions,” concluded Tacquet.

The study is published in the journal Nature Medicine.