Dangerous consequences of “brain fog” during “long Covid” have been identified

The “brain fog” from long Covid may be caused by a weak blood-brain barrier, a new study has found. If substances that control the barrier moving into and out of the brain are disrupted, changes in nerve function can result.

From forgetfulness to difficulty concentrating, many long-term Covid-19 sufferers are experiencing brain fog. Now researchers say the symptom may be due to the blood-brain barrier becoming impenetrable.

According to The Guardian, this barrier controls what substances or materials enter and leave the brain. “It’s all about regulating the balance of substances in the blood versus the brain,” says Professor Matthew Campbell, co-author of the study at Trinity College Dublin. “If this is disrupted, it can lead to changes in neural function, and if this happens in areas of the brain that support memory consolidation/storage, then it can wreak havoc.”

Writing in the journal Nature Neuroscience, Campbell 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 findings, the team found that samples taken from 14 Covid patients who self-reported brain fog contained higher levels of a protein called S100β than Covid patients without this symptom or people who did not have Covid.

This protein is produced by brain cells and is not usually found in the blood, suggesting that these patients had a breakdown of the blood-brain barrier, explains The Guardian.

The researchers then recruited 10 people who had recovered from Covid and 22 people with long Covid – 11 of whom reported brain fog. At that time, no one had received the Covid vaccine or been hospitalized for Covid.

These participants underwent magnetic resonance imaging in which dye was injected intravenously.

The results show that long Covid patients with brain fog did show signs of blood-brain barrier disruption, but not those who did not have the symptom or who recovered.

Professor Campbell added that it was possible that people with a tighter blood-brain barrier might be better protected from brain fog if Covid persisted for a long time, explaining why the symptom did not occur in all patients.

Further work in a subgroup of participants showed that long Covid patients with brain fog also showed signs of increased levels of proteins involved in blood clotting.

Campbell said the results were not surprising because abnormalities in proteins involved in blood clotting can go hand in hand with the destruction of cells lining blood vessels. “The idea that many of these neurological conditions, including brain fog, can be treated by simply adjusting the integrity of the blood-brain barrier is really exciting,” he said.

Although the study focused on long-term Covid patients, Campbell said the findings may have implications for people with brain fog associated with other conditions, although extensive work would be needed to confirm this.

Professor Paul Harrison from the University of Oxford, author of earlier work suggesting blood clots in the brain may be one cause of brain fog in people with long Covid, said the new research was important.

“This shows that abnormalities in the lining of brain blood vessels occur in people with brain fog after Covid, and adds to evidence that abnormal blood clotting also contributes,” he said.

But he added that the results were from patients who had Covid in the first wave, meaning it was plausible but it was unclear whether the same mechanisms were at play in others, such as patients with more recent variants of the virus, or those who have been vaccinated.

Paul Harrison notes: “A number of processes are likely to explain brain fog and other features of post-Covid syndrome.”

Professor Claire Steeves, from King’s College London, said the small number of participants meant it was possible the differences between the groups were discovered by chance, while brain fog was not clearly defined and was self-reported.

“It is therefore difficult to be sure how applicable these results will be to the millions of people who have experienced this phenomenon,” she said.