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The Guardian: Long Covid ‘brain fog’ may be due to leaky blood-brain barrier, study finds

From forgetfulness to difficulties concentrating, many people who have long Covid experience “brain fog”. Now researchers say the symptom could be down to the blood-brain barrier becoming leaky.

By Nicola KS Davis


The barrier controls which substances or materials enter and exit the brain. “It’s all about regulating a balance of material in blood compared to brain,” said Prof Matthew Campbell, co-author of the research at Trinity College Dublin.

Writing in the journal Nature Neuroscience, Campbell and colleagues report how they analysed serum and plasma samples from 76 patients who were hospitalised with Covid in March or April 2020, as well 25 people before the pandemic.

Among other findings, the team discovered that samples from the 14 Covid patients who self-reported brain fog contained higher levels of a protein called S100β than those from Covid patients without this symptom, or people who had not had Covid.

This protein is produced by cells within the brain, and is not normally found in the blood, suggesting these patients had a breakdown of the blood-brain barrier.

The researchers then recruited 10 people who had recovered from Covid and 22 people with long Covid – 11 of whom reported having brain fog. None had, at that point, received a Covid vaccine, or been hospitalised for Covid. These participants underwent an MRI scan in which a dye was administered intravenously.

The results reveal long Covid patients with brain fog did indeed show signs of a leaky blood-brain barrier, but not those without this symptom, or who had recovered.

Campbell added that it was possible people with a tighter blood-brain barrier might be better protected from brain fog should they develop long Covid, explaining why the symptom did not arise in all patients.

While the study focuses on long Covid patients, Campbell said the results might have relevance to people with brain fog relating to other conditions – such as ME (Myalgic Encephalomyelitis) – although extensive work would be needed to confirm that.

The ME Association Comment

These are interesting research findings and while they do not confirm that there is a breakdown in the blood brain barrier (BBB), and that this is causing cognitive dysfunction/brain fog in Long Covid, it is a plausible theory.

So, I hope this work will continue…..

As far as ME/CFS is concerned, when I was working with Professors Peter and Mina Behan in Glasgow back in the 1980s and 1990s, Prof Mina Behan also felt that disruption to the BBB could be taking place in ME/CFS

The MEA Ramsay Research Fund provided a grant.

Unfortunately, Mina became seriously ill while the research was in progress and it was never completed.

If this Long Covid research does arrive at firmer conclusions the MEA RRF would be very willing to consider funding a similar study involving ME/CFS.

Dr Charles Shepherd,
Trustee and
Hon. Medical Adviser
to the ME Association.
Member of the 2018-2021 NICE Guideline Committee.
Member of the 2002 Independent Working Group on ME/CFS.

Dr Charles Shepherd

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