Blood clots during COVID-19 may be a cause of ‘brain fog’

MQ researcher Dr Max Taquet and his team from the University of Oxford have found evidence that the ongoing cognitive problems that some people experience after contracting COVID could be caused by blood clots.

Many people with long-COVID experience memory issues and slowed thinking, often referred to as brain fog. Now we are one step closer to understanding the exact cause.

High levels of two proteins at the time of COVID-19 have been found in patients who later experienced cognitive problems, including ‘brain fog’, giving a major clue as to one cause of their symptoms: blood clots.

“Long COVID is thought to affect 3.1% of the population. That’s 2 million brits with long-term symptoms including brain fog, fatigue and depression. These finding from Max and the team at Oxford are a vital step for finding a solution for the people impacted.” Lea Milligan, CEO MQ Mental Health Research


Max looked at blood tests from 1,837 people who had been hospitalised with COVID-19. The aim was to find potential proteins (biomarkers) 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. Other aspects of the profiles suggested they are likely to reflect blood clots. The main findings were replicated using electronic health records in a separate population.

Dr 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.

“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, from the University of Oxford 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 participants involved in this research are part of the UKRI funded PHOSP-COVID (Post-hospitalisation COVID-19) study, led by University of Leicester.

MQ’s Research Programme Lead Dr Parisa Mansoori, who is a named co-author on this paper, explains more about PHOSP.

“When the pandemic hit in 2020, through the NIHR Translational Collaborations we quickly brought together a group of academics from different clinical specialties to study longer term impact of being hospitalised with COVID-19 through the PHOSP-COVID project. The Brain Working Group of PHOSP brought together a wide range of UK researchers, clinicians and charities who wanted to investigate the long-term effects of COVID on mental, cognitive and neurological health – and to explore how these effects were related to individual patient characteristics and whole-body health. This UK-wide Working Group met every week for almost 2 years, sometimes with 70 enthusiastic attendees sharing ideas based on what seen in the clinic, the latest evidence, or shared by people who have had COVID. The idea for Max’s project was conceived through these rich regular collaborative meetings and was supported by MQ who secured funding for it.”

PHOSP participants had their memory assessed at six and 12 months after hospitalisation from COVID infection 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’.”

The study was funded by MQ Mental Health Research and the Wolfson Foundation, and supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centres in Leicester and Oxford Health. You can read the full paper here. 

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