Blood clots in the lungs have been linked to ‘brain fog’, fatigue and breathlessness following severe COVID-19 in a UK-based study.

Researchers from the Universities of Oxford and Leicester analysed the blood tests and cognitive outcomes of 1,837 patients in the PHOSP-COVID cohort who had been hospitalised for COVID-19 during the first wave of the pandemic in a bid to discover the underlying mechanisms for cognitive issues after the acute phase of infection.

They discovered two distinct blood biomarker profiles predictive of cognitive deficits at six and twelve months following COVID-19 hospitalisation.

In one subset, patients had raised D-dimer levels but a normal or relatively lower CRP level, which suggested that D-dimer levels were raised because of hypercoagulation instead of inflammation.

These patients had only subjective cognitive deficits but also reported a reduced ability to work and fatigue.

Given that they also experienced shortness of breath, the researchers said they believed it likely that blood clots in these patients were situated in the lungs, Dr Max Taquet, NIHR Academic Clinical Fellow in Psychiatry, University of Oxford, told journalists at a press briefing.

“Blood clots in the lungs can lead to lack of oxygen supply to the brain, which eventually might lead to cognitive problems. But we also know that blood clots in the lungs can cause a degree of fatigue and that fatigue itself can cause cognitive problems down the line,” he said.

The second biomarker profile consisted of raised fibrinogen and normal levels of C reactive protein, driven by hypercoagulation rather than inflammation.

These patients had objective and subjective cognitive issues six and 12 months post-infection but reported no shortness of breath, indicating that clots could have been present anywhere in the body.

Interestingly, the team also found evidence to suggest that raised fibrinogen is a common mechanism by which people develop cognitive issues, as cognitive deficits at six months were identified in those with raised levels of the protein regardless of whether they had COVID.

This was not the case for D-dimer; here, the data showed that people who did not have COVID but had raised levels of this protein were not at increased risk of developing cognitive issues compared to those with normal levels, thus showing some specificity to the COVID virus.

“COVID-19 increases the risk much more than other respiratory infections. That doesn’t mean that people with other respiratory infections can never develop brain fog or cognitive problems, but it [affects] much fewer than those with COVID-19”, said Dr. Taquet.

Numerous mechanisms behind ‘long COVID’

The researchers believe that the fibrinogen and D-dimer biomarker profiles identified in the study are just two of many potentially related to long COVID.

“I suspect there’s going to be a number of different mechanisms – and this is definitely what we’re beginning to find – and that those different mechanisms are likely to be identified with different tests and are then likely to need different types of treatments, which are going to be both drug treatments, but also non-drug treatments,” noted paper author Professor Chris Brightling, Professor of Respiratory Medicine, University of Leicester.

Findings of this research “really support that and help us to actually start to make really big steps towards having potential tests and opening up which groups of patients might respond to different treatments,” he said.

The study was published in Nature Medicine (link here)