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      Are the salivary glands the key players in spreading COVID‐19 asymptomatic infection in dental practice?

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          Abstract

          Dear Editor, We read with great interest the article by Song et al 1 on the assessment of the expression of angiotensin‐converting enzyme 2 (ACE2) and transmembrane serine proteases 2 (TMPRSS2) in salivary glands using publicly available databases. Undiagnosed infections were reported to facilitate the rapid dissemination of the coronavirus disease 2019 (COVID‐19) 2 caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). The SARS‐CoV‐2 depends on ACE2 and TMPRSS2 for cell entry and priming. 3 The salivary glands were suggested to act as reservoirs for COVID‐19 asymptomatic infections and transmission since high expression of the ACE2 receptor was found in minor salivary glands. 4 The Transcriptome data analysis by Song et al 1 showed that ACE2 and TMPRSS2 were expressed in salivary glands. Thus, the virus might entry into the salivary glands. Corroborating this, in other communication, 5 ACE2 and TMPRSS2 were found to be expressed in the salivary glands. The analysis carried out in available databases (Genotype‐Tissue Expression portal and Human Protein Atlas repository) by Song et al, 1 Xu et al, 4 and Pascolo et al 5 are valid to reinforce the hypothesis of salivary gland infection by SARS‐CoV‐2. 6 However, we cannot forget that several factors, such as gene regulatory networks, tissue pH, hormones, concentration of co‐factors and metabolic events change the expression, concentration and activity of enzymes. 7 , 8 , 9 To the best of our knowledge, besides the higher number of available publications, literature still lacks this information in the context of salivary glands infection by SARS‐CoV‐2. Even though saliva is important biological fluid for SARS‐CoV‐2 detection, the source of virus in saliva has not been fully investigated in most studies. Chen et al 6 collected saliva directly from the submandibular salivary glands ducts of 31 confirmed cases of patients with COVID‐19. Interestingly, the expression of SARS‐CoV‐2 was found only in four patients (12.90%), being higher in severe cases (3/4). This suggested SARS‐CoV‐2 coming directly from the salivary gland might be due to high viral loads at the late stage of the disease 6 and not from individuals with mild, limited, or lack of symptoms. It is encouraged, however, to carry on research on SARS‐CoV‐2 shedding from salivary glands to undersdand their contribution to viral load in saliva given literature on this topic is still scarce. It has been widely reported that dental practice accounts for an increased risk of SARS‐CoV‐2 infection due to the close contact with the patient's airways and performance of aerosol‐generating procedures. 10 , 11 , 12 Dental activities worldwide were profoundly affected by the COVID‐19 pandemic. 13 , 14 Several dental care facilities closed or limited appointments to urgent and emergency care. In addition, several recommendations were issued to provide dental care while mitigating the disease spread. 15 , 16 , 17 Mild, limited and asymptomatic infections, from individuals who never experience noticeable symptoms, have been widely reported for COVID‐19. 18 , 19 , 20 However, even if asymptomatic infections are common, transmission from asymptomatic individuals was reported to be probably uncommon. 21 Overall, even though the current literature shows that salivary glands can be infected, we cannot affirm that they act as reservoirs for COVID‐19 asymptomatic infections. Despite the indication of mouthwashes might cause confusion among the practitioners, along with other biosafety practices they would be able to decrease the risk of SARS‐CoV‐2 transmission by limiting viral load in saliva droplets and aerosols produced during dental procedures. 12 , 22 The maintenance of oral healthcare is a serious problem that requires attention and appropriate measures. 23 The adoption of the preventive measures in dental setting to reduce viral load in mouth could be useful to provide elective care in asymptomatic patients in times of COVID‐19. Studies are necessary to understand the real role of salivary glands in COVID‐19 asymptomatic infections and transmission. CONFLICT OF INTEREST The authors declare that there are no conflict of interest. AUTHOR CONTRIBUTION MS Pedrosa CR Sipert and FN Nogueira conceived the study and discussed the results. MS Pedrosa drafted the first manuscript. MS Pedrosa CR Sipert and FN Nogueira critically read and revised the manuscript, and gave final approval for publication. DISCLAIMER The funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

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          Most cited references20

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          SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

          Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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            Presumed Asymptomatic Carrier Transmission of COVID-19

            This study describes possible transmission of novel coronavirus disease 2019 (COVID-19) from an asymptomatic Wuhan resident to 5 family members in Anyang, a Chinese city in the neighboring province of Hubei.
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              Is Open Access

              Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2)

              Estimation of the prevalence and contagiousness of undocumented novel coronavirus (SARS-CoV2) infections is critical for understanding the overall prevalence and pandemic potential of this disease. Here we use observations of reported infection within China, in conjunction with mobility data, a networked dynamic metapopulation model and Bayesian inference, to infer critical epidemiological characteristics associated with SARS-CoV2, including the fraction of undocumented infections and their contagiousness. We estimate 86% of all infections were undocumented (95% CI: [82%–90%]) prior to 23 January 2020 travel restrictions. Per person, the transmission rate of undocumented infections was 55% of documented infections ([46%–62%]), yet, due to their greater numbers, undocumented infections were the infection source for 79% of documented cases. These findings explain the rapid geographic spread of SARS-CoV2 and indicate containment of this virus will be particularly challenging.
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                Author and article information

                Contributors
                marlus@usp.br
                Journal
                J Med Virol
                J. Med. Virol
                10.1002/(ISSN)1096-9071
                JMV
                Journal of Medical Virology
                John Wiley and Sons Inc. (Hoboken )
                0146-6615
                1096-9071
                02 August 2020
                : 10.1002/jmv.26316
                Affiliations
                [ 1 ] Department of Biomaterials and Oral Biology, School of Dentistry University of São Paulo São Paulo Brazil
                [ 2 ] Department of Restorative Dentistry, School of Dentistry University of São Paulo São Paulo Brazil
                Author notes
                [*] [* ] Correspondence Marlus da Silva Pedrosa, Departmento de Biomateriais e Biologia Oral, Faculdade de Odontologia, Universidade de São Paulo (USP), Av. Prof. Lineu Prestes, 2227 Cidade Universitária, São Paulo, 05508‐900, Brasil.

                Email: marlus@ 123456usp.br

                Author information
                http://orcid.org/0000-0002-4052-7208
                http://orcid.org/0000-0002-5719-6505
                http://orcid.org/0000-0002-6595-9154
                Article
                JMV26316
                10.1002/jmv.26316
                7405131
                32681673
                b04b6576-6300-4c2a-8e2c-2da846e11bc2
                © 2020 Wiley Periodicals LLC

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 12 July 2020
                : 16 July 2020
                Page count
                Figures: 0, Tables: 0, Pages: 2, Words: 1361
                Funding
                Funded by: Fundação de Amparo à Pesquisa do Estado de São Paulo , open-funder-registry 10.13039/501100001807;
                Award ID: 2019/14556‐7
                Categories
                Letter to the Editor
                Letter to the Editor
                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.6 mode:remove_FC converted:05.08.2020

                Microbiology & Virology
                Microbiology & Virology

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