Olfactory Support Cells, Not Primary Neurons, Are Targeted in COVID-19

Post by Lincoln Tracy

What's the science?

The most common neurological symptom of the coronavirus disease 2019 (COVID-19) is the partial or complete loss of smell and/or taste. This finding has resulted in researchers developing simple smell tests (like scratch-and-sniff stickers) that can be used to screen for COVID-19. But how does SARS-CoV-2 (the virus that causes COVID-19) affect the cells and circuits that allow us to smell and taste? This week in Neuron, Cooper and colleagues speculate on the pathophysiological mechanisms of SARS-CoV-2 on the olfactory system.

What do we already know?

Previous research has shown that coronaviruses infect the upper airways and cause the common cold, which is associated with short- and long-term changes in smell and taste. Researchers have proposed several different mechanisms for these changes in smell, including increased mucus production and direct damage to olfactory neurons that detect odors. Damaged olfactory neurons can be replaced over time, which may cause distortions in our sense of smell. However, the history behind the loss of smell associated with COVID-19 suggests that SARS-CoV-2 affects the olfactory system in a different way compared to the less severe and more common coronaviruses. 

What’s new?

The authors propose that rather than directly infecting olfactory sensory neurons, SARS-CoV-2 impacts our ability to smell by affecting a variety of cells in the olfactory epithelium that houses neurons. Many of the cell types within the olfactory epithelium support and assist olfactory neurons in different ways. First, the cells in the olfactory epithelium may become inflamed. Inflammation of the epithelium may block the nasal clefts or the narrow passages that allow air to reach the epithelium, which prevents us from detecting smells and odors. Second, the inflammation following SARS-CoV-2 infection may cause the release of inflammatory intermediates such as cytokines. Inflammatory intermediates have been reported to reduce the expression of odorant receptors on olfactory neurons. It is the odorant receptors that detect odors that give rise to our sense of smell. Finally, SARS-CoV-2 infecting the support cells may make the microenvironment of the olfactory epithelium detrimental to functioning. For example, Bowman’s glands secrete mucus that is essential for detecting odors. SARS-CoV-2 infection may cause changes in the secreted mucus, meaning that olfactory functioning is inhibited. The result of each of the proposed mechanisms is an indirect interruption of olfactory neuronal function, interfering with our sense of smell and taste.

lincoln.png

What's the bottom line?

Current evidence suggests that neural function is indirectly altered as a result of SARS-CoV-2 infecting smaller cells that surround and support neurons, rather than the neurons themselves. Cooper and colleagues use COVID-19 to highlight how little we know about the non-neuronal cells and structures that support our ability to taste and smell.  Continuing to study SARS-CoV-2 will help us better understand how viruses can specifically disrupt our senses and more generally affect our neuronal connections. 

Datta_quote_Jul14.jpg

Cooper et al. COVID-19 and the Chemical Senses: Supporting Players Take Center Stage. Neuron (2020). Access the original scientific publication here.