Coronavirus may enter the brain by building tiny tunnels from the nose

How the virus behind covid-19 enters the brain was somewhat of a mystery, but new evidence hints it may build tiny tubes from nose cells to brain cells that it can shuttle through

By Alice Klein

We may finally know how covid-19 enters the brain: new research suggests the virus responsible stimulates the growth of tiny tubes between nose and brain cells that it can tunnel through.

Covid-19 has been linked with a range of neurological symptoms including brain fog and confusion. Autopsy studies have also detected the coronavirus in people’s brains. But how it gets there has been somewhat of a mystery. Previous studies suggest the ACE2 receptor that the virus normally uses to get into cells is barely detectable in the brain, unlike the cells lining the nose, mouth and lungs.

Now, Chiara Zurzolo at the Pasteur Institute in France and her colleagues have discovered that the coronavirus seems to have a sneaky way of getting into cells that lack the ACE2 receptor via cells that do have it.

They conducted experiments in a dish with the coronavirus and two different cell types. One called SH-SY5Y was used to model human brain cells. The other cell type, Vero E6, was used to model cells that line body surfaces, including the nose.

On their own, the model brain cells couldn’t be infected with the coronavirus because they lacked the ACE2 receptor. But when they were incubated in the same dish as the model nose cells, which did have these receptors, they became infected.

Under a particularly powerful electron microscope, the researchers saw that upon entering the model nose cells, the virus stimulated the cells to grow tiny tubes called tunnelling nanotubes that formed connections with the model brain cells.

Zooming up close, they saw the virus using these tunnels to shuttle between the two cell types. Nanotubes are already known to transport certain structures and other viral particles between distant cells.

“I think it’s a very interesting study because it provides a nice, neat mechanism by which the virus can be transferred from one cell to another while bypassing the need for ACE2 receptors,” says Frederic Meunier at the University of Queensland in Australia.

However, because the experiments were limited to cells in a dish, further studies are needed to confirm the same mechanism occurs inside the brain, says Meunier.

Zurzolo says her group is setting up “organ-on-a-chip” experiments that more closely mimic the interactions between cells in the nose and brain.

If tunnelling nanotubes are confirmed to transport the coronavirus from the nose to the brain, we may be able to develop drugs to block them, says Zurzolo. “At the moment, we do not have a specific tunnelling nanotube-blocking molecule, but we are carrying out screening to find some,” she says.

Journal reference: Science Advances, DOI: 10.1126/sciadv.abo0171