Study looks at how COVID-19 invades the brain in severe cases
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. (Photo: Michael Laue/RKI & Carsten Dittmayer/Charité)
TORONTO -- According to a new study from Berlin, the most common path that the novel coronavirus takes when it invades the brain is through the nose.
While it’s known that SARS-CoV-2, the virus that causes COVID-19, is largely a respiratory virus, it’s now recognized at this stage in the pandemic that the virus affects many other regions of the body, from the cardiovascular system to the brain.
More than a third of COVID-19 patients report neurological symptoms, such as headaches, brain fog and a loss of smell and taste, and some patients have even had strokes connected to the illness.
But how the virus made its way into the brain hadn’t been looked at in closer detail until this study, according to researchers.
Published Monday in the journal Nature Neuroscience, the study looked at tissue samples from 33 patients who had died after contracting COVID-19.
In order to track how the virus reached the brain stem, researchers looked at numerous regions of the brain, as well as the structures in the skull that connect the eyes, mouth and nose to the brain stem.
They searched specifically for not only SARS-CoV-2 genetic material, but also the spike protein found on the surface of the virus. Although evidence of the virus could be found throughout the structures that connect the brain to the eyes, mouth and nose, the highest viral load was found in the olfactory mucosa — the upper region of the nasal cavity.
“Using special tissue stains, the researchers were able to produce the first-ever electron microscopy images of intact coronavirus particles within the olfactory mucosa,” a press release states.
The image itself shows yellow clumps of virus attacking a pink nerve cell.
Dr. Frank Heppner, the director of the Department of Neuropathology at Charitie - Universitätsmedizin Berlin, said in the release that the data “support[s] 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.”
Researchers believe that the virus travels through nerve cells in order to reach the brain, but the full pattern of movement is unknown, and could involve transportation through the blood vessels as well.
“Evidence of the virus was also found in the walls of blood vessels in the brain,” Dr. Helena Bradbunch, of the Department of Neuropathology, said in the release.
Another aspect of the research looked at the immune response in the brain itself. The study found that there were activated immune cells in both the brain and the nasal cavity, as well as tissue damage caused by stroke in some of the cases.
The loss of taste and smell that many COVID-19 patients experience can likely be traced to the presence of COVID-19 in the olfactory mucosa, researchers say.
COVID-19 in the brain may also affect severe outcomes as well. Researchers found SARS-CoV-2 in “areas of the brain which control vital functions, such as breathing.”
“It cannot be ruled out that, in patients with severe COVID-19, presence of the virus in these areas of the brain will have an exacerbating impact on respiratory function, adding to breathing problems due to SARS-CoV-2 infection of the lungs,” Heppner said.
Researchers specified that because their study group only included those with severe cases who had died after contracting COVID-19, the results of the study can’t be extrapolated to those with mild cases.
But the results prompt further research into the question of how the virus travels in the body, and how the nasal passages play a role.
The question of noses and COVID-19 has been brought up by other researchers recently. A paper published in Frontiers in Immunology on Monday argued that we should be researching more how immune responses develop in the mucous membranes of the nose and mouth in relation to the virus.
The mucosal immune system is the largest component of the human body’s immune system as a whole, a release on the paper stated. While a lot of COVID-19 research has been dedicated to the lower respiratory tract — particularly the lungs — where more severe cases attack, not a lot have looked at the upper respiratory tract and its specific immune responses, the paper said.
The authors theorized that looking at mucosal immunity could shed more light on how and why some people remain asymptomatic, despite having the virus in their system.
“Could it be that this is due to early mucosal immune responses that succeed in containing and eliminating the infection before it becomes serious?” Michael W. Russell, a professor with the Jacobs School of Medicine and Biomedical Sciences at the University of Buffalo, said in a press release. "We will not know unless these questions are addressed."