Blood clots during COVID-19 may be a cause of ongoing cognitive problems

31 August 2023

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.

Dr Max Taquet and colleagues from the University of Oxford looked at blood tests from 1,837 people who had been hospitalised with COVID-19 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. 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’.”

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.

Notes to editor:

For further information or interviews with the article author, please contact: Lisa Jones, Communications Manager, Department of Psychiatry, 
Tel: +44 (0)1865 618206, Email [email protected] Or [email protected].

  • This new paper ‘Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalisation’ is published in Nature Medicine. It will be available here on publication: https://www.nature.com/articles/s41591-023-02525-y
  • The University Department of Psychiatry’s mission is to conduct world-class research, teach psychiatry to medical students, develop future researchers in a graduate programme, teach doctors in training, promote excellence in clinical practice, and develop and provide innovative clinical services. It supports research in four key areas: neurobiology, psychological treatments, developmental psychiatry and social psychiatry. The Department is committed to the translation of scientific discovery into benefits for patients. www.psych.ox.ac.uk
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The Oxford Health BRC (Biomedical Research Centre):
The Oxford Health Biomedical Research Centre (OH BRC) led by Professor John Geddes is based at the Oxford Health NHS Foundation Trust. The OH BRC is run-in partnership with the University of Oxford and involves 11 additional partner university and NHS Trusts across England. Support for infrastructure is provided by the National Institute for Health and Care Research (NIHR) for 11 research Themes focused on brain health.


The NIHR Leicester Biomedical Research Centre :
The National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre (BRC) is part of the NIHR and hosted by the University Hospitals of Leicester NHS Trust in partnership with the University of Leicester, Loughborough University and the University Hospitals of Northamptonshire NHS Group.

The NIHR Leicester BRC undertakes translational clinical research in priority areas of high disease burden and clinical need. These are:

  • Respiratory and infectious diseases
  • Personalised cancer prevention and treatment
  • Lifestyle (including diabetes)
  • Environment and health
  • Data innovation for multiple long term health conditions and ethnic health
  • Cardiovascular disease

The BRC harnesses the power of experimental science to explore and develop ways to help prevent and treat chronic disease. It brings together 120 highly skilled researchers, 45 academic ‘rising stars’, more than 90 support staff and students and over 450 public contributors. By having scientists working closely with clinicians and the public, the BRC can deliver research that is relevant to both patients and the professionals who treat them. www.leicesterbrc.nihr.ac.uk

About NIHR:

  • The mission of the National Institute for Health and Care Research (NIHR) is to improve the health and wealth of the nation through research. We do this by:
  • Funding high quality, timely research that benefits the NHS, public health and social care;
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  • Collaborating with other public funders, charities and industry to help shape a cohesive and globally competitive research system;
  • Funding applied global health research and training to meet the needs of the poorest people in low and middle income countries.
  • NIHR is funded by the Department of Health and Social Care. Its work in low and middle income countries is principally funded through UK Aid from the UK government.
    https://www.nihr.ac.uk/

About the University of Leicester
The University of Leicester is led by discovery and innovation – an international centre for excellence renowned for research, teaching and broadening access to higher education. It is among the Top 30 universities in the Times Higher Education (THE)’s Research Excellence Framework (REF) 2021 rankings with 89% of research assessed as world-leading or internationally excellent, with wide-ranging impacts on society, health, culture, and the environment. The University is home to more than 20,000 students and approximately 4,000 staff.
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