A new study shows how spike protein crosses the blood-brain barrier
University
of Washington Health Sciences/UW Medicine
Johns Hopkins Medicine
More
and more evidence is coming out that people with COVID-19 are suffering from
cognitive effects, such as brain fog and fatigue.
And researchers
are discovering why. The SARS-CoV-2 virus, like many viruses before it, is bad
news for the brain. In a study published Dec.16 in Nature Neuroscience, researchers found that
the spike protein, often depicted as the red arms of the virus, can cross the
blood-brain barrier in mice.
This strongly
suggests that SARS-CoV-2, the cause of COVID-19, can enter the brain.
The spike protein, often called the S1 protein, dictates which cells the virus can enter. Usually, the virus does the same thing as its binding protein, said lead author William A. Banks, a professor of medicine at the University of Washington School of Medicine and a Puget Sound Veterans Affairs Healthcare System physician and researcher. Banks said binding proteins like S1 usually by themselves cause damage as they detach from the virus and cause inflammation.
"The S1
protein likely causes the brain to release cytokines and inflammatory
products," he said.
In science
circles, the intense inflammation caused by the COVID-19 infection is called a
cytokine storm. The immune system, upon seeing the virus and its proteins,
overreacts in its attempt to kill the invading virus. The infected person is
left with brain fog, fatigue and other cognitive issues.
Banks and his
team saw this reaction with the HIV virus and wanted to see if the same was
happening with SARS CoV-2.
Banks said the
S1 protein in SARS-CoV2 and the gp 120 protein in HIV-1 function similarly.
They are glycoproteins -- proteins that have a lot of sugars on them, hallmarks
of proteins that bind to other receptors. Both these proteins function as the
arms and hand for their viruses by grabbing onto other receptors. Both cross
the blood-brain barrier and S1, like gp120, is likely toxic to brain tissues.
"It was
like déjà vu," said Banks, who has done extensive work on HIV-1, gp120,
and the blood-brain barrier.
The Banks' lab
studies the blood-brain barrier in Alzheimer's, obesity, diabetes, and HIV. But
they put their work on hold and all 15 people in the lab started their
experiments on the S1 protein in April. They enlisted long-time collaborator
Jacob Raber, a professor in the departments of Behavioral Neuroscience,
Neurology, and Radiation Medicine, and his teams at Oregon Health & Science
University.
The study could
explain many of the complications from COVID-19.
"We know
that when you have the COVID infection you have trouble breathing and that's
because there's infection in your lung, but an additional explanation is that
the virus enters the respiratory centers of the brain and causes problems there
as well," said Banks.
Raber said in
their experiments transport of S1 was faster in the olfactory bulb and kidney
of males than females. This observation might relate to the increased
susceptibility of men to more severe COVID-19 outcomes.
As for people
taking the virus lightly, Banks has a message:
"You do not
want to mess with this virus," he said. "Many of the effects that the
COVID virus has could be accentuated or perpetuated or even caused by virus
getting in the brain and those effects could last for a very long time."
This study was
partially supported by a National Institute on Aging-funded COVID-19 supplement
to a shared RF1 grant of Banks and Raber.
