Virus that causes COVID-19 uses a secret 'back door' to infect the brain

SARS-CoV-2, the virus that causes COVID-19, may preferentially use a "back door" into cells to infect the brain, a new mouse study suggests.

The finding could partly explain why many people have neurological symptoms such as fatigue, dizziness, brain fog, or loss of smell or taste during or after a bout with the virus. Scientists think these symptoms may arise when SARS-CoV-2 enters the central nervous system, but how and why the virus moves from the respiratory tract to the brain wasn't clear until now.

In an article published Aug. 23 in the journal Nature Microbiology, researchers discovered mutations in the virus's spike protein, which it uses to enter human cells by binding to a molecule called ACE2 on the cells' surface.

"The SARS-CoV-2 spike protein coats the outside of the virus and allows it to enter a cell," study co-author Judd Hultquist, an assistant professor of infectious diseases at Northwestern University in Chicago, told Live Science in an email. "Normally, the virus can enter the cell in two ways: either at the cell surface (through the front door) or internally after it is taken up into the cell (through the back door)."

Part of the spike protein, called the furin cleavage site, helps the virus enter through the front door. If this site is mutated or removed, the virus can only use the backdoor route.

"Cells in the upper airways and lungs are highly susceptible to SARS-CoV-2, which can enter these cells through the front and back doors," Hultquist said. "To reach and replicate successfully in the brain, it seems like the virus has to enter through the back door. Deleting the furin cleavage site makes the virus more likely to use this pathway — and more likely to infect brain cells."

To study this, the researchers used genetically engineered mice whose cells make human ACE2. After infecting these mice with SARS-CoV-2, they took virus samples from lung and brain tissue and sequenced the viral genomes.