In the last two decades, coronavirus has caused two large-scale pandemics, SARS in 2002 and the Middle East respiratory syndrome (MERS) in 201214. In December 2019, a novel coronavirus (2019-nCov) induced an outbreak of pneumonia in Wuhan, China, restated the risk of coronaviruses posed to public health15. The infection routes and pathogenesis of 2019-nCov are not fully understood by far, and the study of 2019-nCoV host cell receptor ACE2 could be valuable for the prevention and treatment of the COVID-19.

In this study, the analysis of public bulk-seq RNA datasets showed that the mucosa of oral cavity could express the ACE2 and was higher in tongue than other oral sites. The results of this study were consistent with the study of Zou et al.10 in general, many organs with higher expression of ACE2 than lung, such as intestine, heart, and kidney. According to the study of Zhao et al.11, the ACE2 expression in lung is concentrated in a small population of type II alveolar cells (AT2), that may cause the relatively low ACE2 expression of lung in bulk-seq RNA datasets analysis. Even though, the result of Zou et al. indicated that the respiratory tract should also be considered as a vulnerable target to 2019-nCoV infection10.

The results of our single cell RNA-seq profiles validated the ACE2 expression in oral cavity, and the level of ACE2 expression in oral tissues was higher in tongue than buccal or gingival tissues. Furthermore, we have also demonstrated that the ACE2-positive cells were enriched in epithelial cells, which was also reported by previous study10,11,12,16. These findings indicated that oral cavity could be regarded as potentially high risk for 2019-nCov infectious susceptibility.

Interestingly, we found that the ACE2 also expressed in lymphocytes within oral mucosa, and similar results were found in various organs of the digestive system and in lungs11,12. Whether those facts have reminded the 2019-nCoV attacks the lymphocytes and leads to the severe illness of patients needs more in vitro and in vivo evidence and validations, though the proportion of ACE2-positive lymphocytes is quite small.

Previous studies have investigated the ACE2 mRNA and protein expression in various tissues by bulk samples17,18, however, the distribution of ACE2 through bulk data could not indicate the cell type-specific expression of ACE2. Recently developed single-cell RNA-sequencing technology enabled the generation of vast amounts of the transcriptomic data at cellular resolution19. The ACE2 expression profile in various organs, tissues, and cell types, provides the bioinformatics evidence for the potential infection routes of 2019-nCov, which might also be associated with presented symptoms.

Although studies have reported multiple symptoms of hospitalized patients with 2019-nCoV infection3,20, some cases at home might be asymptomatic. It is worth noting that, a previous study showed that 99% of the patients had no clinical manifestation of oral human papillomavirus (HPV), but HPV DNA was detected in 81% of oral mucosa samples, and anti-HPV IgA was detected in the saliva of 44% of the patients21. Likewise, although 2019-ncov infection hardly presented oral symptoms, the ACE2 expression in the oral cavity indicated that the oral infection route of 2019-nCoV cannot be excluded. Moreover, a latest pilot experiment showed that 4 out of 62 stool specimens tested positive to 2019-nCoV, and another four patients in a separate cohort who tested positive to rectal swabs had the 2019-nCoV being detected in the gastrointestinal tract, saliva, or urine20. Thus, our results support that in addition to the respiratory droplets and direct contact, fecal–oral transmission might also be the route of transmission of 2019-nCoV.

Our results are mainly based on public datasets and single cell RNA-sequencing data of in-house oral tissues with minimal diseased lesion which from our previous project found no significant expression difference among the common epithelial markers in our past study and other previous study22,23,24. It is warrant that further histological methods are used to confirm our results and enhance the persuasion of the conclusion.

The ACE2-expressing cells in oral tissues, especially in epithelial cells of tongue, might provide possible routes of entry for the 2019-nCov, which indicate oral cavity might be a potential risk route of 2019-nCov infection. Those preliminary findings have explained the basic mechanism that the oral cavity is a potentially high risk for 2019-nCoV infectious susceptibility and provide a piece of evidence for the future prevention strategy in clinical practice as well as daily life.