New research published in the journal Nature Neuroscience is the first to demonstrate how the SARS-CoV-2 virus can directly damage cells in the brain. An international group of scientists found vascular cells that comprise the blood-brain barrier can be destroyed by the virus and this may lead to the neurological symptoms, both short and long-term, commonly reported from COVID-19.
The effects of SARS-CoV-2 on the brain are still emerging as researchers race to understand the full impact of this novel coronavirus on the human body. Cognitive problems such as brain fog are commonly reported in those experiencing long-term, lingering COVID-19 symptoms, and brain tissue studies from deceased patients have detected molecular markers of inflammation, indicating the virus can affect the brain.
However, it is still unclear whether the SARS-CoV-2 virus enters the brain and directly causes damage, or if neurological symptoms are generated by systemic immune responses to the virus triggering some kind of neuroinflammation.
A strong study earlier this year led by neuroscientists from Yale University certainly demonstrated how the virus could directly infect brain cells, but there are ongoing debates over whether this actually happens in real-world infections. Beyond studying brain tissue from deceased COVID-19 patients it is difficult to find out if the virus is explicitly infecting cells in the brain.
This new study focused on a particular type of brain cell known as cerebral vascular endothelial cells. These cells are an essential component of the blood-brain barrier – the protective wall that helps keep foreign or toxic molecules out of the brain.
In order to investigate the effect of SARS-CoV-2 on these endothelial cells the researchers first looked at brain tissue from patients who died of COVID-19. Jan Wenzel, a neuroscientist working on the project, says increased numbers of dead cells were found in COVID-19 patients, compared to a well-matched control.
“Having clinical data in mind that hints at microvascular changes in COVID-19 patients, we started to look into the microvasculature of brain samples in deceased COVID-19 patients,” Wenzel explains on Twitter. “We found an increased amount of dead capillaries, so-called string vessels.”
Moving to cell and animal experiments the researchers then demonstrated exactly how the SARS-CoV-2 virus could kill these endothelial cells. And it is hypothesized that the consequence of this damage is decreased blood flow to brain regions, leading to cognitive problems or heightened risk of neurodegenerative disease.
“… we think, that the direct infection of brain endothelial cells by SARS-CoV-2 leads to the expression of its main protease which cleaves NEMO, an essential protein necessary for the survival of brain endothelial cells,” Wenzel says. “Our finding might explain at least partially neurological symptoms that not only appear during the acute but also long-term phase of COVID-19 including the increased risk for getting stroke or epileptic seizures and long COVID.”
The study does optimistically indicate this damage could be reversible, and mouse models demonstrate possible ways to inhibit this damaging interaction between the virus and endothelial cells. Wenzel also speculates vaccination could reduce the damage the virus causes to the blood-brain barrier.
“As far as we know vaccination protects against the vascular damage since the immune system acts against the virus in our blood, from where endothelial cells are infected,” says Wenzel.
While this research is robust and thorough, it is by no means a definitive answer to what effects SARS-CoV-2 has on the human brain. It is difficult to confidently conclude these signs of brain damage seen in the deceased brain tissue samples were caused by the virus, or know the long-term effects of this damage.
Several researchers have recently warned there could be increases in rates of neurological diseases such as Parkinson’s in the future due to the long-term effects of COVID-19. Australian researcher Zoe Hyde, who did not work on this new study, says these findings affirm the potential of COVID-19 to cause damage to the brain, and that this plausibly could lead to greater rates of dementia in the future.
“COVID-19 can cause brain damage,” Hyde recently stated on Twitter. “I wouldn’t be surprised if we see an increased number of adults developing vascular dementia in the years ahead.”
Other researchers are more cautious about inferring long-term neurological problems from this particular study. Geriatrician Kate Gregorevic argues the new findings offer no insight into whether a mild case of COVID-19 affects a person’s future dementia risk.
“The study referenced describes a series of brain autopsies done on people who died of COVID, often of hypoxia, for most after weeks on a ventilator,” Gregorevic points out. “It cannot be extrapolated to people with mild COVID.”
Vincent Prevot, a co-author on the new study, is also a little more circumspect, saying there are plenty of unanswered questions raised by these findings. He suggests it is important to be aware of the potential effect of SARS-CoV-2 on the brain and monitor patients over the years to come.
“This awareness of the severity of SARS-CoV-2 infection and its impacts on proper brain function is vital to enable the best possible management of infected patients in the years to come,” says Prevot.
The new study was published in the journal Nature Neuroscience.
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