From forgetfulness to difficulty concentrating, many people who have had Covid for a long time experience “brain fog”. Now researchers say the symptom may be that the blood-brain barrier is leaking.
The barrier controls what substances or materials enter and leave the brain. “It’s all about regulating a balance of material in blood compared to brain,” says Prof Matthew Campbell, co-author of the research at Trinity College Dublin.
“If it’s out of balance, it can drive changes in neural function and if it happens in brain regions that enable memory consolidation/storage, it can wreak havoc.”
Writing in the journal Nature NeuroscienceCampbell and colleagues report how they analyzed serum and plasma samples from 76 patients who were hospitalized with Covid in March or April 2020, as well as 25 people before the pandemic.
Among other things, the team discovered that samples from the 14 Covid patients who reported brain fog contained higher levels of a protein called S100β than those from Covid patients without this symptom, or people who did not have Covid.
This protein is produced by cells in the brain and is not normally found in the blood, suggesting that 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-term Covid – 11 of whom reported having brain fog. No one had received a Covid vaccine at that time, or had been hospitalized for Covid.
These participants underwent an MRI scan in which a dye was administered intravenously.
The results show that long-term Covid patients with brain fog did show signs of a leaky blood brain barrier, but not those without this symptom or who had recovered.
Campbell added that it is possible that people with a tighter blood-brain barrier may be better protected from brain fog should they develop prolonged Covid, which explains why the symptom does not occur in all patients.
Further work in a subgroup of participants revealed that tall Covid patients with brain fog also showed signs of increased levels of proteins involved in clotting.
Campbell added the results are not a surprise, since disruption of proteins involved in clotting can go hand in hand with disruption of cells that line blood vessels. “The whole concept that a lot of these neurological conditions, including brain fog, can be treated simply by regulating the integrity of the blood-brain barrier is really exciting,” he said.
While the study focuses on long-term Covid patients, Campbell said the results may be relevant to people with brain fog associated with other conditions – such as ME – although extensive work will be needed to confirm this.
Prof Paul Harrison of the University of Oxford, an author of earlier work suggesting blood clots in the brain may be one cause of brain fog in people with prolonged Covid, said the new study is important.
“This shows that abnormalities in the lining of blood vessels in the brain occur in people with post-Covid brain fog, and adds to the evidence that abnormal blood clotting also contributes,” he said.
But he added the results came from patients who had Covid in the first wave, meaning it is plausible but unclear whether the same mechanisms occur in others, such as those with later variants of the virus, or who have been vaccinated.
Harrison said: “Probably a series of processes explain brain fog and other features of post-Covid syndrome.”
Prof Claire Steves from King’s College London added that the small number of participants involved meant it was possible that findings of differences between groups were coincidental, while brain fog was not clearly defined and was self-reported by participants.
“Therefore, it is difficult to be sure how applicable these results are to the millions of people who have experienced this phenomenon,” she said.
