Abstract
Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly transfers from human to human via respiratory and gastrointestinal routes. The S-glycoprotein in the virus is the key factor for the entry of SARS-CoV-2 into the cell, which contains two functional domains: S1 is an angiotensin-converting enzyme 2 (ACE2) receptor binding domain, and S2 is necessary for fusion of the coronavirus and cell membranes. Moreover, it has been reported that ACE2 is likely to be the receptor for SARS-CoV-2. In addition, mRNA level expression of Furin enzyme and ACE2 receptor had been reported in airway epithelia, cardiac tissue, and enteric canals. However, the expression patterns of ACE2 and Furin in different cell types of oral tissues are still unclear.Methods: In order to investigate the potential infective channel of the new coronavirus via the oropharyngeal cavity, we analyze the expression of ACE2 and Furin in human oral mucosa using the public single-cell sequence datasets. Furthermore, immunohistochemistry was performed in mucosal tissue from different oral anatomical sites to confirm the expression of ACE2 and Furin at the protein level.Results: The bioinformatics results indicated the differential expression of ACE2 and Furin on epithelial cells from different oral anatomical sites. Immunohistochemistry results revealed that both the ACE2-positive and Furin-positive cells in the target tissues were mainly positioned in the epithelial layers, partly expressed in fibroblasts, further confirming the bioinformatics results.Conclusions: Based on these findings, we speculated that SARS-CoV-2 could invade oral mucosal cells through two possible routes: binding to the ACE2 receptor and fusion with cell membrane activated by Furin protease. Our results indicated that oral mucosa tissues are susceptible to SARS-CoV-2 that could facilitate COVID-19 infection via respiratory and fecal–oral routes.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) causes coronavirus disease 2019 (COVID-19) pandemic and mainly triggers acute respiratory distress syndrome (ARDS) and viral sepsis that bring challenges to the patient’s treatment [1, 2]
For a better understanding of the potential COVID-19 infection risk in the oral cavity, we explored whether angiotensin-converting enzyme 2 (ACE2) and Furin are expressed and the composition and proportion of their expressing cell in different oral tissues based on the public scRNA-seq profiles from Gene Expression Omnibus (GEO) public databases
Using the unsupervised graph-based clustering, we found that at least 13 distinct cell clusters existed in the oral tissues (Figure 1A), including epithelial cells, fibroblasts, T-cells, and B cells
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) causes coronavirus disease 2019 (COVID-19) pandemic and mainly triggers acute respiratory distress syndrome (ARDS) and viral sepsis that bring challenges to the patient’s treatment [1, 2]. Many research groups had reported gastrointestinal manifestation of COVID-19 purposing the fecal– oral route as an alternative route of SARS-CoV-2 transmission [5,6,7,8]. These findings suggest that the epithelial cells of the oropharyngeal cavity provide the binding site to enter and propagate the SARS-CoV-2. Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly transfers from human to human via respiratory and gastrointestinal routes. The expression patterns of ACE2 and Furin in different cell types of oral tissues are still unclear
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