How Covid-19 Might Sneak Into The Brain Shown In New Images

Immunofluorescence staining shows a nerve cell (pink) inside the olfactory mucosa which has been infected with SARS-CoV-2 (yellow). Supporting (epithelial) cells appear blue. Jonas Franz/Universitätsmedizin Göttingen

New research has highlighted how SARS-CoV-2, the virus that causes Covid-19, manages to sneak its way into the brain. 

Just like a handful of other viruses, it appears SARS-CoV-2 makes its way into the central nervous system via the nose, the new study shows. This is a useful — although not totally unexpected — piece of the puzzle that explains why one in three people with Covid-19 report neurological symptoms, such as loss of smell or taste, headaches, fatigue, and dizziness.

Scientists at Charité-Universitätsmedizin Berlin reached this conclusion by studying the bodies of patients who had died from Covid-19. As reported in the journal Nature Neuroscience, the researchers used electron microscope imagery to show intact SARS-CoV-2 particles in the olfactory mucosa, the mucus-secreting membrane in the upper stretches of the nose, for the very first time.

Of all the different structures that connect the eyes, mouth, and nose to the brain, they discovered the olfactory mucosa contain the highest viral load, indicating it's the most likely port of entry. They also found activated immune cells in the brain and the olfactory mucosa, further suggesting the infection likely took this route. This part of the nose is surprisingly close to the brain, so it appears the virus can travel from the olfactory mucosa to the olfactory nerve, the short nerve that deals with sensory information about smells, and into the brain. This allows the virus to bypass typical barriers of the central nervous system and provides a direct line to the brain.

An electron microscope image (ultrathin section, artificially colored) shows a section of a ciliated cell in the olfactory mucosa. Large numbers of intact SARS-CoV-2 particles (red) are found both inside the cell and on cellular processes. Yellow: kinocilia. Michael Laue/RKI & Carsten Dittmayer/Charité

“These data support the notion that SARS-CoV-2 is able to use the olfactory mucosa as a port of entry into the brain. Once inside the olfactory mucosa, the virus appears to use neuroanatomical connections, such as the olfactory nerve, in order to reach the brain,” Professor Frank Heppner, study author and director of the Department of Neuropathology at Charité-Universitätsmedizin Berlin, said in a statement.

A lot about this process remains uncertain, however. For one, it’s unclear how the virus moves on from the nerve cells. It’s also worth stressing that this study was on people who died of Covid-19, so the findings might not necessarily apply to people with mild or moderate cases of the disease. 

Finally, many viral infections can be found in the nose, such as the common cold, but they don’t always become neurological conditions that infect the brain. This indicates there are some solid defenses to stop viruses and other unwanted invaders from breaching the brain. However, it’s unknown why SARS-CoV-2 is one of the few examples of viral infections, alongside herpes simplex virus and rabies, which is able to reach the brain through this olfactory pathway.

“Our data suggest that the virus moves from nerve cell to nerve cell in order to reach the brain,” added Dr Helena Radbruch, study author from Charité’s Department of Neuropathology. "It is likely, however, that the virus is also transported via the blood vessels, as evidence of the virus was also found in the walls of blood vessels in the brain.”

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