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From forgetfulness to difficulty concentrating, many long-term Covid sufferers experience “brain fog.” Now researchers say the symptom could be due to a leaky blood-brain barrier.
The barrier controls what substances or materials enter and leave the brain. “It’s about regulating the balance of material in the blood compared to the brain,” said Professor Matthew Campbell, co-author of the research at Trinity College Dublin.
“If that is out of balance, then it can cause changes in neural function and if this happens in regions of the brain that allow for memory consolidation/storage, then it can wreak havoc.”
Writing in Nature Neuroscience magazineCampbell and his 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 from 25 people before the pandemic.
Among other findings, the team found that samples from the 14 Covid patients who reported mental confusion 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 that these patients suffered 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 mental confusion. None, at that time, had received a Covid vaccine or been hospitalized for Covid.
These participants underwent an MRI in which they were given a dye intravenously.
The results reveal that long Covid patients with mental confusion did show signs of a leaky blood-brain barrier, but not those without this symptom or who had recovered.
Campbell added that it was possible that people with a tighter blood-brain barrier would be better protected from brain fog if they developed long Covid, explaining why the symptom did not arise in all patients.
Further work on a subgroup of participants revealed that long Covid patients with mental confusion also showed signs of elevated levels of proteins involved in clotting.
Campbell said the results were not a surprise since alterations in proteins involved in clotting could go hand in hand with alterations in the cells that line blood vessels. “The idea that many of these neurological conditions, including brain fog, could be treated simply by regulating the integrity of the blood-brain barrier is really exciting,” she said.
While the study focuses on long Covid patients, Campbell said the results could have relevance to people with brain fog related to other conditions, such as MS, although extensive work would be needed to confirm this.
Professor Paul Harrison of Oxford University, author of earlier work suggesting blood clots in the brain may be a cause of mental confusion in people with long Covid, he said the new study was important.
“It shows that abnormalities occur in the lining of blood vessels in the brain in people with post-Covid brain fog, and adds to the evidence that abnormal blood clotting also contributes,” he said.
But he added that the results came from patients who had Covid in the first wave, meaning it was plausible but it was unclear whether the same mechanisms occurred in others, such as those with later variants of the virus, or who were vaccinated.
Harrison said: “A variety of processes probably explain the brain fog and other features of post-Covid syndrome.”
Professor Claire Steves of King’s College London said the small number of participants involved meant it was possible that findings of differences between groups were due to chance, 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,” he said.