dcyphr | High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa


Studies have shown that the 2019-nCoV virus primarily infects host cells with the ACE2 receptor. This receptor allows the virus to enter the host cell. Using RNA sequencing data, the researchers found that many cells in the oral mucosa (mucous membrane) express ACE2. Many receptors were specifically found in the epithelial cells of the tongue. This indicates that cells in the oral cavity are possibly at high risk for 2019-nCoV infection.


The researchers aim to study if the virus could enter cells in the mucosa in the oral cavity. 


Many patients have gotten Coronavirus Disease 19 (COVID-19) since December 2019. They experienced pneumonia, fatigue, respiratory failure, and other complications. The 2019-nCoV virus has a receptor binding domain (RBD) is similar to that of SARS-CoV. The study Zhou et al. showed that 2019-nCoV primarily infects cells through the angiotensin-converting enzyme II (ACE2) receptor. Other receptors are not used. The study Xu et al. showed that the spike protein interacts with human ACE2. The spike protein (S protein) is responsible for virus binding to the host receptor. Therefore, cells with a high number of ACE2 receptors may have a high risk of coronavirus infection.


In Figure 1, the researchers show that many organs express ACE2. These organs include the intestine, kidney, colon, gallbladder, and heart muscle. When examining the oral cavity, they found high ACE2 expression in the tongue, floor of the mouth, and the base of the tongue. The tongue had the most ACE2 expression, but this difference was not significant compared to other sites in the mouth. The analysis came from the public RNA sequencing (RNA-Seq) databases.

Researchers conducted RNA sequencing on many cells, including epithelial cells, T cells, and fibroblasts. Out of the ACE2 positive cells in the mouth, 95.86%% came from the tongue rather than the cheek or gums. Most of the ACE2 positive cells were epithelial cells. But, T cells, B cells, and fibroblasts were also ACE2 positive (Figure 2). Thus, the epithelial cells of the tongue have the highest concentration of the ACE2 receptor.


An interesting result is that lymphocytes in the oral mucosa had ACE2 receptors. The lungs and the digestive system organs also had lymphocytes that were ACE2 positive. More studies need to be done on how 2019-nCoV infects lymphocytes.

Oral symptoms are rare in COVID-19. But, an oral route of infection cannot be dismissed. In another study, 4 out of 62 stool specimens of patients with COVID-19 tested positive for 2019-nCoV. Thus, an oral-fecal transmission route for 2019-nCoV is possible.

Histology studies are still needed to elaborate on these findings. The results further inform how COVID-19 can be prevented.


The researchers used single cell RNA sequencing for various tissues. They also used RNA sequencing data from two databases. They studied para-carcinoma normal tissue in 13 organ types from the Cancer Genome Atlas (TCGA) and normal tissue in 14 organ types from the Functional Annotation of The Mammalian Genome Cape Analysis of Gene Expression (FANTOM5 CAGE). The researchers used the software R for analyses.