Abstract
The proximity to the patient during dental care, high generation of aerosols, and the identification of SARS-CoV-2 in saliva have suggested the oral cavity as a potential reservoir for COVID-19 transmission. Mouthwashes are widely-used solutions due to their ability to reduce the number of microorganisms in the oral cavity. Although there is still no clinical evidence that they can prevent the transmission of SARS-CoV-2, preoperative antimicrobial mouth rinses with chlorhexidine gluconate (CHX), cetylpyridinium chloride (CPC), povidone-iodine (PVP-I), and hydrogen peroxide (H2O2) have been recommended to reduce the number of microorganisms in aerosols and drops during oral procedures. This paper therefore aims to provide a comprehensive review of the current recommendations on the use of mouthwashes against the COVID-19 pandemic and to analyse the advantages and disadvantages of most conventional antiseptic mouthwashes used in dentistry.
Keywords: Coronavirus, COVID-19, Dentistry, Mouthwashes, Oral health
Introduction
Antiseptic mouthwashes have been widely used as a standard measure before routine dental treatment, especially preoperatively.1, 2 They have an essential role in reducing the number of microorganisms in the oral cavity.3 Recent publications have suggested that rinsing the oral cavity may control and reduce the risk of transmission of SARS-CoV-2.4, 5 However, specific evidence for the safety and efficacy of the use of antiseptic mouthwashes in COVID-19 positive patients is lacking and unclear, so this paper aims to provide a comprehensive review of the current recommendations on the use of mouthwashes against the COVID-19 pandemic and to analyse the advantages and disadvantages of most conventional antiseptic mouthwashes used in dentistry.
Pathogenesis of coronavirus disease 2019
Coronaviruses are a group of enveloped RNA viruses that present a typical structure with the “spike protein” in its membrane envelope.6, 7 The interaction between this protein and angiotensin-converting enzyme 2 (ACE2) receptors is responsible for the entry of the virus into cells.8 The distribution of ACE2 receptors in different parts of the body may indicate possible routes of infection.9, 10 The membrane bound to ACE2 is found in different tissue cells, including mucosal tissues, gingiva, non-keratinising squamous epithelium, and epithelial cells of the tongue and salivary glands.8, 11 A high SARS-CoV-2 viral load has also been detected in saliva,12 and it its presence has even been suggested in periodontal pockets.13 These findings agree with previous investigations that have suggested that virus transmission can be closely connected with saliva interactions14, 15 making oral tissues a possible reservoir from which SARS-CoV-2 transmission may occur during coughing, sneezing, talking, and even during dental care.4, 12, 16
Oral antiseptics used against viral infections
Mouthwashes are widely used solutions for rinsing the mouth, especially before oral surgery, due to their ability to reduce the number of microorganisms in the oral cavity1, 2 and colony-forming units in dental aerosols.3 Although there is still no clinical evidence that the use of mouthwashes could prevent SARS-CoV-2 transmission, the American Dental Association (ADA)17 and the Center for Disease Control and Prevention (CDC)18 have recommended the use of preprocedural mouthwashes before oral procedures.
Chlorhexidine (CHX)
CHX is a broad-spectrum antiseptic that acts against Gram-positive and Gram-negative bacteria, aerobes, facultative anaerobes, and fungus by increasing the permeability of the bacterial cell wall, causing its lysis.19, 20 It is used in dentistry to reduce dental plaque and treat periodontal disease.21
Evidence indicates an in vitro effect against lipid-enveloped viruses such as influenza A, parainfluenza, herpes virus 1, cytomegalovirus, and hepatitis B.22 Although COVID-19 is an enveloped virus, 0.12% CHX gluconate was suggested to have little or no effect against coronaviruses when compared with other mouthwashes.4, 23, 24 However, Yoon et al6 found SARS-CoV-2 suppression for two hours after using 15 ml 0.12% CHX once, suggesting that its use would be beneficial for the control of COVID-19 transmission.
Hydrogen peroxide (H2O2)
H2O2 has been used in dentistry alone or combined with salts since the start of the century.25 As a mouthwash, it is an odourless, clear, and colourless liquid.26 Lack of an adverse soft tissue effect was found in many studies of 1%–1.5% H2O2 used as a daily rinse over two years’ follow-up.27, 28
An in vitro study found that 3% H2O2 effectively inactivated adenovirus types 3 and 6, adeno-associated virus type 4, rhinoviruses 1A, 1B, and type 7, myxoviruses, influenza A and B, respiratory syncytial virus, strain long, and coronavirus strain 229E within 1–30 minutes, discovering that coronaviruses and influenza viruses were the most sensitive.29 Since SARS-CoV2 is vulnerable to oxidation, preprocedural mouthrinses containing oxidative agents such as 1% H2O2 have been suggested to reduce the salivary viral load.4, 17
Cetylpyridinium chloride (CPC)
CPC is a quaternary ammonium compound that is safe for use in humans.30, 31 CPC 0.05% has been used to reduce dental plaque and gingivitis32 as an alternative in patients who develop mucosal irritation and stains related to CHX.33 The antiviral effect of CPC has been demonstrated in influenza patients, significantly reducing the duration and severity of cough and sore throat.31, 34 Hypotheses about a possible action over SARS-CoV-2 are based on its lysosomotropic mechanism of action and its ability to destroy viral capsids.35 These findings indicate that CPC could be effective against other enveloped viruses such as coronaviruses.
Iodopovidone
Povidone-iodine (PVP-I) is a water-soluble iodine complex that has been widely used as a pre-surgical skin antiseptic and as a mouthwash.36 It is typically used in a 1% concentration37 for mucositis, prophylaxis of oropharyngeal infections, and prevention of ventilator-associated pneumonia. Its antimicrobial action occurs after free iodine dissociates from polyvinylpyrrolidone, then iodine rapidly penetrates microbes to disrupt proteins and oxidises nucleic acid structures causing microbial death.38, 39 Previously studies have shown that PVP-I has higher virucidal activity than other commonly used antiseptic agents, including CHX and benzalkonium chloride.40 It is safe, reporting a prevalence of 0.4% allergy cases,41 does not produce tooth or tongue discolouration or taste disturbances42 and, unlike alcohol-based products, can be used when using electrocautery.43 Its effectiveness has been well demonstrated through many in vitro studies against multiple viruses, including SARS-CoV, MERS-CoV, and influenza virus A (H1N1).36, 40, 44 Recent investigations have proposed that 0.23% PVP-I mouthwash for at least 15 seconds before procedures may reduce salivary viral load,44 indicating its use in COVID-19-positive patients.4, 38, 45, 46
Suggested recommendations
Gently gargle for 30 seconds in the oral cavity and 30 seconds in the back of the throat with: 1.5%17 or 3%47 H2O2 15 ml; PVP-I, 0.2%,17 0.4%,45 or 0.5%46, 48 9 ml; 0.12% CHX 15 ml;6 or 0.05% CPC 15 ml.31, 35
Conclusions
Within the limitations of this brief review and despite little clinical evidence, we suggest the use of preprocedural mouthwashes in dental practice to reduce SARS-CoV-2 viral load from previous dental procedures and to reduce the cross-infection risk while treating patients during the pandemic. Clinical studies, including control subjects and in large scale, are required to evaluate the efficacy of antiseptic mouthwashes on SARS-CoV-2. Research is urgently needed to determine its potential for use against this new virus.
Conflict of interest
We have no conflicts of interest.
Ethics statement/confirmation of patients' permission
Not applicable.
Funding
This research received no external funding.
References
- 1.Kosutic D., Uglesic V., Perkovic D., et al. Preoperative antiseptics in clean/contaminated maxillofacial and oral surgery: prospective randomized study. Int J Oral Maxillofac Surg. 2009;38:160–165. doi: 10.1016/j.ijom.2008.11.023. [DOI] [PubMed] [Google Scholar]
- 2.Dominiak M., Shuleva S., Silvestros S., et al. A prospective observational study on perioperative use of antibacterial agents in implant surgery. Adv Clin Exp Med. 2020;29:355–363. doi: 10.17219/acem/115087. [DOI] [PubMed] [Google Scholar]
- 3.Marui V.C., Souto M.L.S., Rovai E.S., et al. Efficacy of preprocedural mouthrinses in the reduction of microorganisms in aerosol: a systematic review. J Am Dent Assoc. 2019;150:1015–1026. doi: 10.1016/j.adaj.2019.06.024. e1. [DOI] [PubMed] [Google Scholar]
- 4.Peng X., Xu X., Li Y., et al. Transmission routes of 2019-nCoV and controls in dental practice. Int J Oral Sci. 2020;12:9. doi: 10.1038/s41368-020-0075-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Ather A., Patel B., Ruparel N.B., et al. Coronavirus disease 19 (COVID-19): implications for clinical dental care. J Endod. 2020;46:584–595. doi: 10.1016/j.joen.2020.03.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Yoon J.G., Yoon J., Song J.Y., et al. Clinical significance of a high SARS-CoV-2 viral load in the saliva. J Korean Med Sci. 2020;35:e195. doi: 10.3346/jkms.2020.35.e195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Li F. Structure, function, and evolution of coronavirus spike proteins. Annu Rev Virol. 2016;3:237–261. doi: 10.1146/annurev-virology-110615-042301. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Chen Y., Guo Y., Pan Y., et al. Structure analysis of the receptor binding of 2019-nCoV. Biochem Biophys Res Commun. 2020;525(February):135–140. doi: 10.1016/j.bbrc.2020.02.071. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Xu H., Zhong L., Deng J., et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020;12:8. doi: 10.1038/s41368-020-0074-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Wan Y., Shang J., Graham R., et al. Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. J Virol. 2020;94:e00127–e220. doi: 10.1128/JVI.00127-20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Hamming I., Timens W., Bulthuis M.L., et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203:631–637. doi: 10.1002/path.1570. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Li Y., Ren B., Peng X., et al. Saliva is a non-negligible factor in the spread of COVID-19. Mol Oral Microbiol. 2020;35:141–145. doi: 10.1111/omi.12289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Badran Z., Gaudin A., Struillou X., et al. Periodontal pockets: a potential reservoir for SARS-CoV-2? Med Hypoth. 2020;143:109907. doi: 10.1016/j.mehy.2020.109907. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Siqueira W.L., Moffa E.B., Mussi M.C., et al. Zika virus infection spread through saliva – a truth or myth? Braz Oral Res. 2016;30 doi: 10.1590/1807-3107BOR-2016.vol30.0046. S1806-83242016000100801. [DOI] [PubMed] [Google Scholar]
- 15.Anschau V., Sanjuán R. Fibrinogen gamma chain promotes aggregation of vesicular stomatitis virus in saliva. Viruses. 2020;12:282. doi: 10.3390/v12030282. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Baghizadeh Fini M. Oral saliva and COVID-19. Oral Oncol. 2020;108:104821. doi: 10.1016/j.oraloncology.2020.104821. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.American Dental Association . 2020. ADA interim guidance for minimizing risk of COVID-19 transmission. Available from URL: https://www.kavo.com/en-us/resource-center/ada-interim-guidance-minimizing-risk-covid-19-transmission [last accessed 13.08.20] [Google Scholar]
- 18.Centers for Disease Control and Prevention. Interim infection prevention and control guidance for dental settings during the COVID-19 response. Available from URL: https://www.cdc.gov/coronavirus/2019-ncov/hcp/dental-settings.html [last accessed 13.08.20]
- 19.Milstone A.M., Passaretti C.L., Perl T.M. Chlorhexidine: expanding the armamentarium for infection control and prevention. Clin Infect Dis. 2008;46:274–281. doi: 10.1086/524736. [DOI] [PubMed] [Google Scholar]
- 20.Vitkov L., Hermann A., Krautgartner W.D., et al. Chlorhexidine-induced ultrastructural alterations in oral biofilm. Microsc Res Tech. 2005;68:85–89. doi: 10.1002/jemt.20238. [DOI] [PubMed] [Google Scholar]
- 21.Da Costa L.F.N.P., Amaral C.D.S.F., Barbirato D.D.S., et al. Chlorhexidine mouthwash as an adjunct to mechanical therapy in chronic periodontitis: a meta-analysis. J Am Dent Assoc. 2017;148:308–318. doi: 10.1016/j.adaj.2017.01.021. [DOI] [PubMed] [Google Scholar]
- 22.Bernstein D., Schiff G., Echler G., et al. In vitro virucidal effectiveness of a 0.12%-chlorhexidine gluconate mouthrinse. J Dent Res. 1990;69:874–876. doi: 10.1177/00220345900690030901. [DOI] [PubMed] [Google Scholar]
- 23.Fehr A.R., Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol. 2015;1282:1–23. doi: 10.1007/978-1-4939-2438-7_1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Kampf G., Todt D., Pfaender S., et al. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents. J Hosp Infect. 2020;104:246–251. doi: 10.1016/j.jhin.2020.01.022. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Marshall M.V., Cancro L.P., Fischman S.L. Hydrogen peroxide: a review of its use in dentistry. J Periodontol. 1995;66:786–796. doi: 10.1902/jop.1995.66.9.786. [DOI] [PubMed] [Google Scholar]
- 26.Walsh L.J. Safety issues relating to the use of hydrogen peroxide in dentistry. Aust Dent J. 2000;45:257–289. doi: 10.1111/j.1834-7819.2000.tb00261.x. [DOI] [PubMed] [Google Scholar]
- 27.Rosling B.G., Slots J., Webber R.L., et al. Microbiological and clinical effects of topical subgingival antimicrobial treatment on human periodontal disease. J Clin Periodontol. 1983;10:487–514. doi: 10.1111/j.1600-051x.1983.tb02180.x. [DOI] [PubMed] [Google Scholar]
- 28.Gusberti F.A., Sampathkumar P., Siegrist B.E., et al. Microbiological and clinical effects of chlorhexidine digluconate and hydrogen peroxide mouthrinses on developing plaque and gingivitis. J Clin Periodontol. 1988;15:60–67. doi: 10.1111/j.1600-051x.1988.tb01556.x. [DOI] [PubMed] [Google Scholar]
- 29.Mentel R., Shirrmakher R., Kevich A., et al. Virus inactivation by hydrogen peroxide. Vopr Virusol. 1977:731–733. [in Russian] [PubMed] [Google Scholar]
- 30.Gerba C.P. Quaternary ammonium biocides: efficacy in application. Appl Environ Microbiol. 2015;81:464–469. doi: 10.1128/AEM.02633-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Mukherjee P.K., Esper F., Buchheit K., et al. Randomized, double-blind, placebo-controlled clinical trial to assess the safety and effectiveness of a novel dual-action oral topical formulation against upper respiratory infections. BMC Infect Dis. 2017;17:74. doi: 10.1186/s12879-016-2177-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Silva M.F., dos Santos N.B., Stewart B., et al. A clinical investigation of the efficacy of a commercial mouthrinse containing 0.05% cetylpyridinium chloride to control established dental plaque and gingivitis. J Clin Dent. 2009;20:55–61. [PubMed] [Google Scholar]
- 33.Feres M., Figueiredo L.C., Faveri M., et al. The effectiveness of a preprocedural mouthrinse containing cetylpyridinium chloride in reducing bacteria in the dental office. J Am Dent Assoc. 2010;141:415–422. doi: 10.14219/jada.archive.2010.0193. [DOI] [PubMed] [Google Scholar]
- 34.Popkin D.L., Zilka S., Dimaano M., et al. Cetylpyridinium chloride (CPC) exhibits potent, rapid activity against influenza viruses in vitro and in vivo. Pathog Immun. 2017;2:252–269. doi: 10.20411/pai.v2i2.200. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Baker N., Williams A.J., Tropsha A., et al. Repurposing quaternary ammonium compounds as potential treatments for COVID-19. Pharm Res. 2020;37:104. doi: 10.1007/s11095-020-02842-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Parhar H.S., Tasche K., Brody R.M., et al. Topical preparations to reduce SARS-CoV-2 aerosolization in head and neck mucosal surgery. Head Neck. 2020;42:1268–1272. doi: 10.1002/hed.26200. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Ader A.W., Paul T.L., Reinhardt W., et al. Effect of mouth rinsing with two polyvinylpyrrolidone-iodine mixtures on iodine absorption and thyroid function. J Clin Endocrinol Metab. 1988;66:632–635. doi: 10.1210/jcem-66-3-632. [DOI] [PubMed] [Google Scholar]
- 38.Kirk-Bayley J, Sunkaraneni VS, Challacombe SJ. The use of povidone iodine nasal spray and mouthwash during the current COVID-19 pandemic may reduce cross infection and protect healthcare workers (May 4, 2020). Available from URL: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3563092 [last accessed 13.08.20]
- 39.Tsuda S., Soutome S., Hayashida S., et al. Topical povidone iodine inhibits bacterial growth in the oral cavity of patients on mechanical ventilation: a randomized controlled study. BMC Oral Health. 2020;20:62. doi: 10.1186/s12903-020-1043-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Kariwa H., Fujii N., Takashima I. Inactivation of SARS coronavirus by means of povidone-iodine, physical conditions and chemical reagents. Dermatology. 2006;212(Suppl. 1):119–123. doi: 10.1159/000089211. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.Lachapelle J.M. Allergic contact dermatitis from povidone-iodine: a re-evaluation study. Cont Dermat. 2005;52:9–10. doi: 10.1111/j.0105-1873.2005.00479.x. [DOI] [PubMed] [Google Scholar]
- 42.Slots J. Selection of antimicrobial agents in periodontal therapy. J Periodontal Res. 2002;37:389–398. doi: 10.1034/j.1600-0765.2002.00004.x. [DOI] [PubMed] [Google Scholar]
- 43.Shiraishi T., Nakagawa Y. Evaluation of the bactericidal activity of povidone-iodine and commercially available gargle preparations. Dermatology. 2002;204(Suppl. 1):37–41. doi: 10.1159/000057723. [DOI] [PubMed] [Google Scholar]
- 44.Eggers M., Koburger-Janssen T., Eickmann M., et al. In vitro bactericidal and virucidal efficacy of povidone-iodine gargle/mouthwash against respiratory and oral tract pathogens. Infect Dis Ther. 2018;7:249–259. doi: 10.1007/s40121-018-0200-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.Mady L.J., Kubik M.W., Baddour K., et al. Consideration of povidone-iodine as a public health intervention for COVID-19: utilization as “Personal Protective Equipment” for frontline providers exposed in high-risk head and neck and skull base oncology care. Oral Oncol. 2020;105:104724. doi: 10.1016/j.oraloncology.2020.104724. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46.Challacombe S.J., Kirk-Bayley J., Sunkaraneni V.S., et al. Povidone iodine. Br Dent J. 2020;228:656–657. doi: 10.1038/s41415-020-1589-4. [DOI] [PubMed] [Google Scholar]
- 47.Caruso A.A., Del Prete A., Lazzarino A.I. Hydrogen peroxide and viral infections: a literature review with research hypothesis definition in relation to the current COVID-19 pandemic. Med Hypoth. 2020;144:109910. doi: 10.1016/j.mehy.2020.109910. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48.Bidra A.S., Pelletier J.S., Westover J.B., et al. Rapid in-vitro inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using povidone-iodine oral antiseptic rinse. J Prosthodont. 2020;29:529–533. doi: 10.1111/jopr.13209. [DOI] [PMC free article] [PubMed] [Google Scholar]