Experients showed that the ACE2 receptor used by SARS-CoV-2 to infect cells is hundreds of times more abundant in a particular region of the nose compared to cells from surrounding regions.
More specifically, cells in the olfactory neuroepithelium have up to 700 times more ACE2 receptors compared to cells in other parts of the nose or in the trachea.
These cells, which are found in the upper nose, are necessary for the development of the sense of smell. This may explain why people infected with the virus often lose the ability to smell and taste. The findings may also help to advance the search for the best target for drugs to treat COVID-19.
“Loss of the sense of smell is associated with COVID-19, generally in the absence of other nasal symptoms, and our research may advance the search for a definitive reason for how and why that happens, and where we might best direct some treatments,” said study co-author Dr. Andrew Lane, who is the director of the Division of Rhinology and Skull Base Surgery at the Johns Hopkins University School of Medicine.
Scientists previously determined that SARS-CoV-2 latches onto a biological hook on the surface of many types of human cells called an angiotensin-converting enzyme 2 receptor (ACE2).
To investigate this phenomenon further, the scientists used an advanced imaging technique to produce high-resolution images of cells lining the nasal and tracheal airways. Using fluorescent stains, they were able to identify ACE2 receptors.
Depending on the biopsy sample, cells in the olfactory neuroepithelium were found to have a 200-fold to 700-fold increase in ACE2 proteins compared with other samples from the nose and trachea.
If the cells lining the nose prove to be a key entry point for SARS-CoV-2, Dr. Lane said there may be ways to target those particular cells with topical antiviral drugs or other therapies directly to that area.
“These findings, taken together with ACE2 protein cellular localization presented here, suggests that active virus infection and replication occurs in the apical layer of nasal and olfactory mucosa,” wrote the researchers.
“The differential expression of ACE2 in the olfactory neuroepithelium and respiratory epithelium may help account for the spectrum of nasal-related symptoms, while also raising the intriguing possibility that COVID-19 may be amenable to novel therapeutic approaches.”
The study is published in the European Respiratory Journal.