The mystery surrounding the “brain fog” suffered by people with long Covid may finally have been revealed – with researchers saying that leaky blood vessels, combined with a hyperactive immune system, could be the cause.
The scientists said their discovery was important for understanding brain fog and the cognitive decline seen in some people with the condition, and it’s hoped this would help with the development of future treatments.
Although patients report a variety of symptoms after Covid infection, generally, they all mention lingering symptoms like fatigue, shortness of breath, problems with memory and thinking, and joint/muscle pain, reports The Independent.
Any of these symptoms that linger for more than 12 weeks after infection can be considered long Covid.
A small study from scientists from Trinity College Dublin and investigators from research centre FutureNeuro found disruption to the integrity of the blood vessels in the brains of people with long Covid and brain fog.
They said people with long Covid who had these leaky vessels had brain fog – but those with the condition but without brain fog, did not.
Matthew Campbell, professor in genetics and head of genetics at Trinity, and principal investigator at FutureNeuro, said: “For the first time, we have been able to show that leaky blood vessels in the human brain, in tandem with a hyperactive immune system, may be the key drivers of brain fog associated with 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.”
Colin Doherty, professor of neurology and head of the school of medicine at Trinity, and principal investigator at FutureNeuro, said: “The findings will possibly change the landscape of how we understand and treat post-viral neurological conditions.
“It also confirms that the neurological symptoms of long Covid are measurable with real and demonstrable metabolic and vascular changes in the brain.”
The findings were published in Nature Neuroscience.
In the study, researchers selected 32 patients who had Covid-19 in March or April of 2020 to undergo specialised brain imaging called a dynamic contrast-enhancing MRI.
Ten of the patients had recovered from Covid-19, 11 had long Covid, and 11 had long Covid with brain fog. They found that the brain images showed more permeability or “leakiness” of the blood-brain barrier in patients who had long Covid with brain fog compared with the other groups.
They also conducted cognitive tests and showed that six of the participants with brain fog had mild-to-moderate cognitive impairment and specifically showed problems with recall, executive functioning and word finding.
When blood markers of inflammation and blood clotting were measured, some markers related to the blood-brain barrier in 76 people who were hospitalised with an acute Covid infection in March and April 2020.
Patients who specifically said they had brain fog with their acute infection had a statistically significant increase in a marker that is indirectly associated with blood-brain barrier dysfunction.
The researchers said these findings suggests that inflammation affecting the blood-brain barrier may contribute to people experiencing brain fog with both acute and long Covid, but brain imaging was not done on the patients with an acute infection in the study.
There are limitations of the study. It was only done with a few people at one hospital in Ireland in the first stages of the pandemic, before vaccines were available, so it may not be generalisable across all people who currently have long Covid.
But it does provide new insights. More research is needed to confirm this finding and understand the implications of it, but experts say it may help researchers as better tests and treatments are developed for long Covid in the future.
“A lot of long Covid symptoms, especially brain fog, are often written off as ‘oh, that’s all in your head’, but this study is suggesting an actual biological mechanism behind it,” Dr Leah Croll, neurologist and assistant professor at Temple University in the US, told ABC News.
“Knowing this is real can be very validating for people who experience this symptom.
“Right now, we're beginning to understand the biological underpinnings of Covid-related brain fog. Gaining that understanding is the vital first step we need to advance future research. I am hopeful that we are on a path towards effective tests and treatments, one study at a time.”
* Study unavailable
Nature article – Leaky blood–brain barrier in long-COVID-associated brain fog (Restricted access)
The Independent article – Researchers discover cause of long Covid’s main symptom (Open access)
See more from MedicalBrief archives:
Long Covid proven by biological markers – Yale study
Post-Covid brain fog linked to blood clots – UK study
Long Covid’s impact on life quality worse than some cancers – UK study
More than half of patients suffer long Covid symptoms – SA study
Cognitive problems from severe COVID similar to 20 years of ageing – UK study