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By David Cox
By David Cox
Many of these [Long COVID] patients were presenting with a range of neurological symptoms. Mavroudis could not help but notice that their symptom patterns – fatigue, sleep disturbances, light and noise sensitivity, exercise intolerance and problems with memory and concentration – were strikingly similar to those associated with another mysterious long-term condition known as post-concussion syndrome or 'Long Concussion'.
Mavroudis was so intrigued by the overlap that he cited it in a scientific review of post-concussion syndrome, published in May 2023. But he wasn't the first to note it. Half a year earlier, a group of concussion experts at the University of Denver, Colorado, had also published their findings on the seemingly unlikely parallels between the two conditions.
When they applied standard concussion tests to Long Covid patients, the University of Denver researchers noticed the same tell-tale issues. One was problems with eye-tracking movements, as assessed via the King-Devick test, which measures the ability to scan numbers on a card from left to right in a zig-zag fashion under time pressure. The results of balance and spatial reasoning examinations also suggested that the patients had effectively experienced a traumatic injury to the brain.
Intrigued, the group suggested that the same diagnostics used for concussion could provide a much-needed way of assessing progress made by these patients. They argued that technologies stimulating the vestibular system - the sensory network in the brain which co-ordinates the position and movement of our head in space - could be trialled a new treatment approach for Long Covid.
In both incidences, he believes that the problems stem from the brainstem, stalk-like structure connecting the brain and spinal cord, becoming constricted. This can either happen due to the skull being too mobile and falling backwards, or a forceful impact.
"The brainstem coordinates connectivity in the brain," says Renz-Polster. “So, when it gets squished, that leads to a complete disruption of the connectivity and flow of information between the various centres that underlie our brain functions." He explains that this is why ME/CFS patients can have a hard time adapting to any kind of stress, whether psychological, muscular, or cognitive. "Every kind of stress sends them into dysfunction," he says.
In recent years, research has also revealed that the brainstem is particularly vulnerable to various neurotropic viruses, ones capable of accessing the brain. Studies have shown that the ACE2 receptor used by the SARS-CoV-2 virus is relatively abundant in the brainstem compared with other regions, while autopsies have even found the virus' RNA and proteins in this part of the brain. It is also thought to be particularly sensitive to damage from the excessive immune activation which can be triggered by infections.
Renz-Polster's theory is two-fold. He believes that an initial trauma - either from a forceful impact or a viral infection – can potentially impair the activity of the brainstem as well as disrupting the fragile membrane separating the brain from the bloodstream. This allows inflammatory molecules to damage the lining of the many small blood vessels which feed the brain, something which has knock-on consequences for mitochondria, the many tiny energy factories which power every cell in the body from neurons to muscle cells.
There are also other patterns which have been seen in ME/CFS, Long Covid and patients who have suffered severe concussions due to traumatic brain injury. One is the reactivation of latent viruses which are permanently ingrained in the genome, such as herpes viruses, which can cause cold sores and genital herpes, or varicella zoster virus, which causes chickenpox and shingles. Once they're reawakened, it's thought that they may lead to inflammation.
Renz-Polster suspects that in all three cases, this viral reactivation could contribute to some of the ongoing symptoms like fatigue and brain fog. While there isn’t a definitive strategy for silencing these viruses once awoken, ideas such as administering the BCG vaccine for tuberculosis have previously been explored as a way of stopping the reactivation of various herpes strains, with some success.