High levels of two proteins at the time of COVID-19 have been found in patients who later experienced cognitive problems, including ‘brain fog’. The findings give a major clue as to one cause of their symptoms: blood clots.
Researchers from the University of Oxford looked at blood tests from 1,837 people who had been hospitalised with COVID-19 to find proteins potentially associated with subsequent cognitive problems, with symptoms including serious and persistent problems with thinking, concentration and memory.
In a new paper published in Nature Medicine, they identified two separate profiles of biomarkers.
The first was having a high level of a protein called fibrinogen, and the second was a raised level of a protein fragment called D-dimer. The main findings were replicated using electronic health records in a separate population.
The main author, Dr Max Taquet said: “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.
“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.”
Dr Taquet added: “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.”
Professor Paul Harrison, who supervised the study, said: “Identifying predictors and possible mechanisms is a key step in understanding post-COVID brain fog. This study provides some significant clues.”
The study was supported by the NIHR Oxford Health Biomedical Research Centre (BRC) and the NIHR Oxford BRC.
The participants involved in this research are part of the UKRI funded PHOSP-COVID (Post-hospitalisation COVID-19) study, led by the University of Leicester.
Their memory was assessed at six and 12 months after hospitalisation using both a formal test and by asking them their own subjective view about their memory.
A participant in the study said: “Since my illness I have been plagued by brain fog, concentration-induced fatigue, poor vocabulary, poor memory. I am unable to process the amount and scale of work that I would previously have done ‘stood on my head’.”