Disruptions in the blood-brain barrier along with a hyperactive immune system are the likely mechanisms behind "brain fog" in patients who are experiencing long COVID, an Irish research team reported today in Nature Neuroscience.
Brain fog has been reported during acute COVID infection and has also been reported in nearly 50% of patients who experience long COVID, or symptoms well past the acute phase of COVID-19.
Clues from blood markers and brain MRI
The blood-brain barrier disruption mechanism was suspected before, but to test the connection, the group first analyzed blood samples to look for any biomarker differences between those who did and didn't report brain fog. They examined blood samples from 76 patients who were hospitalized with acute COVID in early 2020, comparing findings with pre-pandemic samples from 25 other patients to look for any differences in coagulation patterns and immune response.
Those who reported brain fog had higher levels of a protein (S100β) produced by brain cells not normally found in the blood, which hinted at a "leaky" blood-brain barrier.
For the second part of the study, the researchers conducted brain scans using dynamic contrast-enhanced MRI to examine brain circulation in 11 people who had recovered from COVID and 22 who had long COVID, which included 11 people who reported brain fog. They found that long-COVID patients with brain fog had a leaky blood-brain barrier when compared to other long COVID patients and to others who had recovered.
The group's experiments also found that long-COVID patients with brain fog had increased levels of clotting markers in their blood.
Implications for diagnosis and treatment
Matthew Campbell, PhD, one of the study coauthors, said in a Trinity College Dublin press release that the findings show for the first time that leaky vessels in the brain along with a hyperactive immune system may be the key drivers of brain fog in people experiencing long COVID.
"This is critically important, as understanding the underlying cause of these conditions will allow us to develop targeted therapies for patients in the future," he said. Campbell is a genetics professor at Trinity College.
The concept that many other viral infections that lead to post-viral syndromes might drive blood vessel leakage in the brain is potentially game changing.
The findings will likely change the understanding and treatment of post-viral neurologic conditions, said Colin Doherty, MD, a study coauthor who is a neurology professor and head of the school of medicine at Trinity College. "It also confirms that the neurological symptoms of Long Covid are measurable with real and demonstrable metabolic and vascular changes in the brain," he added.
Campbell concluded, "The concept that many other viral infections that lead to post-viral syndromes might drive blood vessel leakage in the brain is potentially game changing and is under active investigation by the team."
