We typically think of SARS-CoV-2, the pathogen that causes COVID, as a respiratory virus. That makes sense, given that it is airborne and typically infects humans via the nose and lungs, and causes respiratory symptoms like cough and sore throat. But maybe we should start thinking of SARS-CoV-2 as a brain virus, too.
After all, we have hard evidence that SARS-2 can infect the brain, causing long-lasting or even permanent damage. This can result in life-threatening strokes and encephalitis, inflammation of the brain, or what is colloquially called "brain fog."
Even anosmia, the loss of taste and smell — considered hallmark symptoms of this disease, though that is changing — is a neurological disorder, a category of conditions affecting the brain and central nervous system. It includes strokes, epilepsy, Alzheimer's, Parkinson's disease and meningitis. Remarkably, SARS-CoV-2 seems able to play a role in all of these neurological dysfunctions and more.
SARS-CoV-2 even seems to activate the same mechanisms in the brain that can causes Parkinson's disease, a brain disorder distinguished by involuntary movements, shakiness and balance difficulties.
Fortunately, developing these neurological conditions from COVID seems to be rare. One's propensity to show such symptoms also depends on how severe the infection is or was, with vaccinated people generally experiencing more mild or temporary symptoms. Medical history may also play a role in how likely it is to develop neurological disorders. However, age does not seem to be a major factor, as children can be affected, too.
We also don't know how much of a role repeat infections could play in this pathology or if certain viral variants are more prone to neurological damage than others. With a "variant soup" apparently ready to ravage North America and Europe this winter, there are lot of questions experts still have about COVID and the brain, but what we're learning isn't reassuring.
What we know is that SARS-CoV-2 seems to activate the same mechanisms in the brain that can causes Parkinson's disease, a brain disorder distinguished by involuntary movements, shakiness and balance difficulties. A new study in the journal Molecular Psychiatry shows for the first time that SARS-2 can trigger the same inflammatory processes seen in patients with Alzheimer's or Parkinson's.
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The good news is that these researchers identify a way to shut this process down using a medication, meaning that in the future there may be a pill to take to prevent brain damage from COVID. To learn how, an international team of researchers led by Professor Trent Woodruff at The University of Queensland performed several different experiments, including with mice, African green monkey kidney cells, and human immune cells called microglia, which act like white blood cells but specifically protect neurons.
In each of these experiments, the scientists were looking for NLRP3, a type of protein called an inflammasome, that defends the brain from attackers by releasing a mess of inflammatory markers. NLRP3 has been widely studied, with some research incriminating this protein for the underlying causes of Parkinson's disease.
Dr. Albornoz Balmaceda described this inflammation cascade like a "fire" in the brain, which sweeps through, killing neurons in its wake.
In each of these trials, whether it was Petri dishes or animal models, NLRP3 was found to be activated. What that means is that SARS-2 infection in the brain seems to also activate NLRP3, which could put people at greater risk of developing Parkinson's disease or related neurological conditions.
"We studied the effect of the virus on the brain's immune cells, 'microglia' which are the key cells involved in the progression of brain diseases like Parkinson's and Alzheimer's," Prof. Woodruff said in a statement. When his team grew human microglia in the lab and infected these cells with SARS-2, they showed signs of intense inflammation that is familiar to neuroscientists studying Parkinson's. "We found the cells effectively became 'angry', activating the same pathway that Parkinson's and Alzheimer's proteins can activate in disease, the inflammasomes," Woodruff said.
Dr. Albornoz Balmaceda, another of the study's authors, described this inflammation cascade like a "fire" in the brain, which sweeps through, killing neurons in its wake. "It's kind of a silent killer, because you don't see any outward symptoms for many years," Balmaceda said in the same release.
An angry fire in the brain sounds bad, but this inflammation actually serves a purpose; it's not a mistake of evolution. When a pathogen like a virus crosses the blood brain barrier, a shield around the brain to filter out unwanted substances, it can start causing damage, infecting neurons and forcing them to shrivel up.
This can trigger the release of NLRP3, which then spreads more inflammatory proteins called caspases. These start telling damaged cells to die in order to stop the spread of the invader, clear out damaged cells and start repairing. This process is called pyroptosis, from the Latin "pyro" for fire and the Greek "ptosis" for falling off, like the leaves of a tree. This type of inflammation causes a chain reaction that can kill a lot of neurons like a bursting string of firecrackers.
A little of this inflammation is natural and can be protective, like a controlled burn. But too much pyroptosis and you go from a contained bonfire to flaming down the whole woods. As more neurons die, the brain starts to malfunction.
To further confirm this theory, the researchers repeated the experiments using a drug that blocked this pathway. Obliquely called MCC950, this drug stops NLRP3 from signaling and has been used in similar studies related to this inflammation pathway. MCC950 binds to NLRP3, preventing inflammation and stopping the brain from essentially angrily setting itself on fire.
MCC950 is actually in development as a way to treat Parkinson's disease, although some research in mice suggests MCC950 could have side effects, such as kidney damage. But other, similar drugs that stop NLRP3 in its tracks could be down the pipeline, so hypothetically, a drug like this could also stop some of the damaging effects of SARS-CoV-2. We now know at least one of the ways that SARS-CoV-2 can wreak havoc on the brain, but we're also one step closer to finding a treatment for it and other neurological conditions like Parkinson's disease.
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