Systematic analysis of ACE2 and TMPRSS2 expression in salivary glands reveals underlying transmission mechanism caused by SARS‐CoV‐2

Abstract

Coronavirus disease 2019 (COVID-19) is a global pandemic that has caused severe health threats and fatalities in almost all communities. Studies have detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in saliva with a viral load that lasts for a long period. However, researchers are yet to establish whether SARS-CoV-2 can directly enter the salivary glands. Therefore, this study aimed to assess the presence of angiotensin-converting enzyme 2 (ACE2)/transmembrane serine proteases 2 (TMPRSS2) expression in salivary glands using publicly available databases. The distribution of ACE2 and TMPRSSs family in salivary gland tissue and other tissues was analyzed. The Genotype-Tissue Expression dataset was employed to explore the ACE2 and TMPRSS2 expression in various body organs and salivary glands in a healthy population. The single-cell sequencing data for salivary gland samples (including submandibular salivary gland and parotid gland) from mice were collected and analyzed. The components and proportions of salivary gland cells expressing the key protease TMPRSSs family were analyzed. Transcriptome data analysis showed that ACE2 and TMPRSS2 were expressed in salivary glands. The expression levels of ACE2 and TMPRSS2 were marginal without significant differences in different age groups or between men and women. Single-cell RNA sequence analysis indicated that TMPRSS2 was mainly expressed in salivary gland epithelial cells. We speculate that SARS-CoV-2 may be entered in salivary glands.

Obesity and COVID-19: Molecular Mechanisms Linking Both Pandemics

“…In addition, the expression of CD147, the suggested alternative receptor for SARS-CoV-2 [113], is positively correlated with the BMI possibly contributing to the COVID-19 morbidity and severity patterns [135]. Moreover, the protease TMPRSS2 is expressed in AT, though at a low level [136], while furin is enhanced expressed in obese AT as well as during adipogenesis [137]. Furin supports not only the entry of SARS-CoV-2 into cells, but also the exit of virus particles from cells by priming the spike protein [138].…”

“…Moreover, the protease TMPRSS2 is expressed in AT, though at a low level [ 136 ], while furin is enhanced expressed in obese AT as well as during adipogenesis [ 137 ]. Furin supports not only the entry of SARS-CoV-2 into cells, but also the exit of virus particles from cells by priming the spike protein [ 138 ].…”

Aspiration of periodontopathic bacteria due to poor oral hygiene potentially contributes to the aggravation of COVID-19

“…During infection with SARS-CoV-2, it is important that the S protein of SARS-CoV-2 is cleaved by proteases, such as TMPRSS2 and furin for adsorption and fusion with the host cells [2,3,38]. Although ACE2, TMPRSS2, and furin are expressed in the oral cavity [39,40], S protein may also be cleaved by the proteases produced by periodontopathic bacteria. Therefore, periodontopathic bacteria may increase the infectivity of SARS-CoV-2.…”

COVID-19 salivary signature: diagnostic and research opportunities

“…Its well known that SARS-CoV-2 infects host cells, including those in the respiratory tract lining, mainly using ACE2 receptor. 53 It is reported that SARS-CoV spike protein S has a high affinity for the ACE2 receptor and is activated by host type II transmembrane serine protease TMPRSS2 on primary target cells to fulfil viral entry 54…”