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• W3095808112 abstract "Patients with systemic diseases, such as hypertension and diabetes, are prone to severe disease when they acquire severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (Chen et al., 2020). A study on the viral load in the secretions from the oropharynx and oral cavity revealed that SARS-CoV-2 spreads faster among patients with underlying diseases, such as diabetes (Liu et al., 2020). We hypothesized that diabetes, obesity and hypertension may promote oral SARS-CoV-2 infection by affecting the ratio of membrane-bound and soluble forms of angiotensin-converting enzyme 2 (ACE2) in the oral cavity. The critical SARS-CoV-2 entry receptor is the membrane-bound ACE2 (mbACE2), and transmembrane serine protease 2 induces intracellular cleavage of ACE2, leading to enhanced viral entry. Disintegrin and metalloproteinase 17 competitively participate in ACE2 processing by facilitating ACE2 ectodomain shedding as a soluble form of ACE2 (sACE2), which exists in extracellular fluids (Heurich et al., 2014) (Figure 1). In the human oral mucosal epithelial cells, the ACE2 receptor has been identified at the mRNA level (Xu et al., 2020), while ACE2 protein expression varies depending on the anatomical location and antibodies used for detection: staining of ACE2 in epithelial cells was obtained using polyclonal but not monoclonal antibodies (Descamps et al., 2020). As the location of the ACE2 extracellular cleavage site corresponds to an area targeted by the monoclonal antibody used, cleavage of the ACE2 ectodomain is a potential explanation for the lack of staining (Descamps et al., 2020). Recently, mbACE2 was found in exfoliated epithelial cells in saliva and the presence of sACE2 in the saliva is suggested as result of their shedding (Srinivasan et al., 2020). In contrast to mbACE2, inversely correlated sACE2 offers protection against viruses (Yang et al., 2014). A human recombinant sACE2 protein has been shown to inhibit SARS-CoV-2 infection of human organoids by intercepting the virus from binding to mbACE2 (Monteil et al., 2020). Since the development of sACE2 from mbACE2 is induced by angiotensin II acting via angiotensin II receptor type 1 (AT-1 receptors) (Patel et al., 2014), blockade of AT-1 receptors by angiotensin receptor blockers or inhibition of angiotensin II generation by ACE inhibitors, commonly prescribed for hypertension and diabetes, inhibits this process and leads to higher mbACE2 and lower sACE2 expression. Other drugs for diabetes and obesity, such as metformin, pioglitazone and liraglutide, may also increase mbACE2 (Pal & Bhadada, 2020; Zhang et al., 2018). Furthermore, drugs used in the treatment of diabetes, obesity, hypertension and diabetes per se induce hyposalivation, which could limit the effectiveness of sACE2 and promote oral SARS-CoV-2 infection (Figure 1). Noteworthy, SARS-CoV-2 infection is associated with xerostomia, likely due to the virus occupancy of ACE2 and consequent angiotensin II increase and aldosterone release that induce sodium and water retention in the salivary glands (Sunavala-Dossabhoy, 2020). Regarding diagnostic impact, the greater involvement of sACE2 in saliva as a virus “decoy,” which may reduce the bonding of SARS-CoV-2 to mbACE2 further in the respiratory tract, could help explain cases of patients exhibiting SARS-CoV-2-positive results in whole saliva or sputum and negative pharyngeal or bronchoalveolar swabs. Likewise, salivary sACE2 may be an important ally and advantage in asymptomatic SARS-CoV-2-positive patients. Further analyses of salivary ACE2 are required to confirm the present hypothesis and understand the nature of the ACE2 species. The authors received no financial support and declare no potential conflicts of interest with respect to the authorship and/or publication of this article. Jelena Roganović: Conceptualization; Investigation; Visualization; Writing-original draft. Miroslav Radenković: Data curation; Investigation; Writing-review & editing. The peer review history for this article is available at https://publons.com/publon/10.1111/odi.13711." @default.
• W3095808112 created "2020-11-09" @default.
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• W3095808112 date "2020-12-17" @default.
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• W3095808112 title "Letter to the Editor: Diabetes, obesity and hypertension may promote oral SARS‐CoV‐2 infection—Salivary soluble ACE2 perspective" @default.
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• W3095808112 doi "https://doi.org/10.1111/odi.13711" @default.
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