COVID-19 doesn’t just affect your lungs, it also has neurological aspects. But how its virus, SARS-CoV-2, spread to the brain is something that doesn’t have a simple explanation. Using a mixture of human and animal cells, a team from the Institut Pasteur suggests that the virus might travel via tunneling nanotubes and infect neurons in the brain.

SARS-CoV-2 infects cells using the angiotensin-converting enzyme 2 (ACE2) receptor but previous studies have shown that this is barely detectable in the brain. So, the question remained, how does the virus get into the brain. As reported in Science Advances, the virus can hijack tunneling nanotubes (TNT), intercellular conduits that can connect distant cells and make their way.

These TNTs allow for the sharing of molecular information between cells but even organelles can sometimes go through them. And viruses too. This is the first time that it has been shown that SARS-CoV-2 can move through these to infect cells.

“Our work provides an explanation for the multiple neurological symptoms associated with the SARS Cov2 infection,” corresponding author Dr Chiara Zurzolo told IFLScience. “Whether and how neurons can be infected was puzzling as they do not express the ACE2 receptor and therefore cannot be infected from the classical route when challenged with the virus. We demonstrated that neurons can be infected when put in culture with infected cells that are permissive to the viral infection.”

The model constructed here has its limitations. It is made by a combination of infected African green monkey kidney cells, which represent epithelial cells that easily let SARS-CoV-2 in. They also had Human SH-Sy5y cells representing neurons. These cells would not let the virus in if the virus could only infect via the ACE2 receptor.

The team believes that SARS-CoV-2 goes from the periphery nasal epithelium into the neurons in the olfactory bulb. And from there it goes to the brain. The team is now planning a more complex model to prove that. They also hope that this work might lead to treatments for both COVID-19 and long COVID.

“We believe that finding molecules blocking the formation of TNTs which are exasperated in diseases could be an approach to halt the progression of several diseases where TNT-mediated transport is involved, including SARS CoV2 infection,” Dr Zurzolo told IFLScience.

On top on building a more complex model, the team is planning to look at tissue samples from infected patients.