Everyone knows the COVID-19 coronavirus is a respiratory disease, but SARS-CoV-2 — the virus associated with the illness responsible for nearly 200,000 deaths in the U.S. — also affects other organ systems, including the central nervous system. Whether this damage extends to the brain, no one was sure. Until now.
A new study found the first clear evidence that some people will suffer an invasion of the coronavirus in their brain cells — hijacking them to copy and reproduce itself, according to a new study shared on a pre-print website.
The virus also absorbs all nearby oxygen, effectively starving neighboring cells to death.
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Coronavirus can infect, hijack brain cells
As of writing it remains unclear how the virus associated with COVID-19 illness enters the brain, or how often it launches its path of destruction, reports The New York Times.
COVID-19 infection in the brain is probably rare, but some people are more vulnerable than others because of genetic backgrounds, high viral load, or other, miscellaneous reasons.
"If the brain does become infected, it could have a lethal consequence," said Akiko Iwasaki, a Yale University immunologist and lead author of the study, the Times reports.
The study is still waiting for expert review, but several researchers agree it is careful and elegant, displaying multiple ways brain cells may suffer from COVID-19 infection.
Coronavirus uses ACE2 protein to invade the brain
The team first used human brain organoids — which are clusters of brain cells in a lab dish designed to mimic the brain's 3D structure. Using these, the research team found clear evidence of infection, along with the associated metabolic changes in infected and neighboring neurons. But no evidence for type I interferon responses were found.
"We demonstrate that neuronal infection can be prevented either by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient," read the study.
The research team also used mice that overexpresses ACE2 — a protein the coronavirus uses to enter human cells — and showed that death is associated with cases when the virus invades the brain without touching the lungs.
"These results provide evidence for the neuroinvasive capacity of SARS-CoV-2, and an unexpected consequence of direct infection of neurons by SARS-CoV-2," concluded the study's abstract.
Brain imaging shows coronavirus hijacks cells, copies itself, starves nearby neurons
Scientists have to use brain imaging and patient symptoms to infer the effects of the virus on the brain, but the ones involved in the study "hadn't really seen much evidence that the virus can infect the brain, even though we knew it was a potential possibility," said Michael Zandi, consultant neurologist at the National Hospital for Neurology and Neurosurgery in Britain, the Times reports. "This data just provides a little bit more evidence that it certainly can."
Zandi and his colleagues also published research in July, suggesting patients with COVID-19 develop serious neurological issues like nerve damage.
The new study saw Iwasaki and her colleagues document brain infection in three different ways: in brain matter from a person who was killed from COVID-19 illness, in a mouse model, and in organoids.
Other deadly pathogens — like the Zika virus — are known to infect the brain's cells. Immune cells typically then flood sites of damage in a bid to cleanse the brain by destroying all infected cells.
However, the coronavirus works in stealth-mode: It uses brain cell machinery to multiply without destroying them — choking adjacent cells of oxygen until they die.
No signs of human immune system response
Autopsies from patients who died from COVID-19 revealed the presence of the coronavirus in cortical neurons — and showed no evidence significant immune response to fight infiltrating coronavirus cells. "It's kind of s silent infection," said Iwasaki. "The virus has a lot of evasion mechanisms."
When the coronavirus attacks the brain, it appears to rapidly decrease the number of synapses — connections between neurons. "Days after infection, and we already see a dramatic reduction in the amount of synapses," said Alysson Muotri, a neuroscientist at the University of California who has studied both the coronavirus and the Zika virus.
Previous studies wrong about brain security from virus
The virus infects a host cell using a protein on its surface called ACE2. This protein also shows up throughout the human body — especially in the lungs — which helps explain why they tend to infect there the most.
While earlier studies suggested the brain was relatively safe from coronavirus infection via its lack of ACE2 proteins, Iwasaki and her colleagues concluded after further scrutiny that the brain is indeed susceptible to infection. "It's pretty clear that it is expressed in the neurons and it's required for entry," she said, reports the Times.
As potential vaccines to the COVID-19 coronavirus ready for distribution across the U.S., we are learning that the virus can be deadly in more ways than previously thought — infecting and hijacking brain cells to reproduce itself while suffocating nearby neurons.
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