Use of mouthwashes against COVID-19 in dentistry

Published:August 25, 2020DOI:https://doi.org/10.1016/j.bjoms.2020.08.016

      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

      Introduction

      Antiseptic mouthwashes have been widely used as a standard measure before routine dental treatment, especially preoperatively.
      • Kosutic D.
      • Uglesic V.
      • Perkovic D.
      • et al.
      Preoperative antiseptics in clean/contaminated maxillofacial and oral surgery: prospective randomized study.
      • Dominiak M.
      • Shuleva S.
      • Silvestros S.
      • et al.
      A prospective observational study on perioperative use of antibacterial agents in implant surgery.
      They have an essential role in reducing the number of microorganisms in the oral cavity.
      • 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.
      Recent publications have suggested that rinsing the oral cavity may control and reduce the risk of transmission of SARS-CoV-2.
      • Peng X.
      • Xu X.
      • Li Y.
      • et al.
      Transmission routes of 2019-nCoV and controls in dental practice.
      • Ather A.
      • Patel B.
      • Ruparel N.B.
      • et al.
      Coronavirus disease 19 (COVID-19): implications for clinical dental care.
      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.
      • Yoon J.G.
      • Yoon J.
      • Song J.Y.
      • et al.
      Clinical significance of a high SARS-CoV-2 viral load in the saliva.
      • Li F.
      Structure, function, and evolution of coronavirus spike proteins.
      The interaction between this protein and angiotensin-converting enzyme 2 (ACE2) receptors is responsible for the entry of the virus into cells.
      • Chen Y.
      • Guo Y.
      • Pan Y.
      • et al.
      Structure analysis of the receptor binding of 2019-nCoV.
      The distribution of ACE2 receptors in different parts of the body may indicate possible routes of infection.
      • Xu H.
      • Zhong L.
      • Deng J.
      • et al.
      High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa.
      • 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.
      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.
      • Chen Y.
      • Guo Y.
      • Pan Y.
      • et al.
      Structure analysis of the receptor binding of 2019-nCoV.
      • 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.
      A high SARS-CoV-2 viral load has also been detected in saliva,
      • Li Y.
      • Ren B.
      • Peng X.
      • et al.
      Saliva is a non-negligible factor in the spread of COVID-19.
      and it its presence has even been suggested in periodontal pockets.
      • Badran Z.
      • Gaudin A.
      • Struillou X.
      • et al.
      Periodontal pockets: a potential reservoir for SARS-CoV-2?.
      These findings agree with previous investigations that have suggested that virus transmission can be closely connected with saliva interactions
      • Siqueira W.L.
      • Moffa E.B.
      • Mussi M.C.
      • et al.
      Zika virus infection spread through saliva – a truth or myth?.
      • Anschau V.
      • Sanjuán R.
      Fibrinogen gamma chain promotes aggregation of vesicular stomatitis virus in saliva.
      making oral tissues a possible reservoir from which SARS-CoV-2 transmission may occur during coughing, sneezing, talking, and even during dental care.
      • Peng X.
      • Xu X.
      • Li Y.
      • et al.
      Transmission routes of 2019-nCoV and controls in dental practice.
      • Li Y.
      • Ren B.
      • Peng X.
      • et al.
      Saliva is a non-negligible factor in the spread of COVID-19.
      • Baghizadeh Fini M.
      Oral saliva and COVID-19.

      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 cavity
      • Kosutic D.
      • Uglesic V.
      • Perkovic D.
      • et al.
      Preoperative antiseptics in clean/contaminated maxillofacial and oral surgery: prospective randomized study.
      • Dominiak M.
      • Shuleva S.
      • Silvestros S.
      • et al.
      A prospective observational study on perioperative use of antibacterial agents in implant surgery.
      and colony-forming units in dental aerosols.
      • 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.
      Although there is still no clinical evidence that the use of mouthwashes could prevent SARS-CoV-2 transmission, the American Dental Association (ADA)
      • American Dental Association
      ADA interim guidance for minimizing risk of COVID-19 transmission.
      and the Center for Disease Control and Prevention (CDC)

      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]

      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.
      • Milstone A.M.
      • Passaretti C.L.
      • Perl T.M.
      Chlorhexidine: expanding the armamentarium for infection control and prevention.
      • Vitkov L.
      • Hermann A.
      • Krautgartner W.D.
      • et al.
      Chlorhexidine-induced ultrastructural alterations in oral biofilm.
      It is used in dentistry to reduce dental plaque and treat periodontal disease.
      • 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.
      Evidence indicates an in vitro effect against lipid-enveloped viruses such as influenza A, parainfluenza, herpes virus 1, cytomegalovirus, and hepatitis B.
      • Bernstein D.
      • Schiff G.
      • Echler G.
      • et al.
      In vitro virucidal effectiveness of a 0.12%-chlorhexidine gluconate mouthrinse.
      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.
      • Peng X.
      • Xu X.
      • Li Y.
      • et al.
      Transmission routes of 2019-nCoV and controls in dental practice.
      • Fehr A.R.
      • Perlman S.
      Coronaviruses: an overview of their replication and pathogenesis.
      • Kampf G.
      • Todt D.
      • Pfaender S.
      • et al.
      Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents.
      However, Yoon et al
      • Yoon J.G.
      • Yoon J.
      • Song J.Y.
      • et al.
      Clinical significance of a high SARS-CoV-2 viral load in the saliva.
      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.
      • Marshall M.V.
      • Cancro L.P.
      • Fischman S.L.
      Hydrogen peroxide: a review of its use in dentistry.
      As a mouthwash, it is an odourless, clear, and colourless liquid.
      • Walsh L.J.
      Safety issues relating to the use of hydrogen peroxide in dentistry.
      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.
      • Rosling B.G.
      • Slots J.
      • Webber R.L.
      • et al.
      Microbiological and clinical effects of topical subgingival antimicrobial treatment on human periodontal disease.
      • 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.
      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.
      • Mentel R.
      • Shirrmakher R.
      • Kevich A.
      • et al.
      Virus inactivation by hydrogen peroxide.
      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.
      • Peng X.
      • Xu X.
      • Li Y.
      • et al.
      Transmission routes of 2019-nCoV and controls in dental practice.
      • American Dental Association
      ADA interim guidance for minimizing risk of COVID-19 transmission.

       Cetylpyridinium chloride (CPC)

      CPC is a quaternary ammonium compound that is safe for use in humans.
      • Gerba C.P.
      Quaternary ammonium biocides: efficacy in application.
      • 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.
      CPC 0.05% has been used to reduce dental plaque and gingivitis
      • 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.
      as an alternative in patients who develop mucosal irritation and stains related to CHX.
      • 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.
      The antiviral effect of CPC has been demonstrated in influenza patients, significantly reducing the duration and severity of cough and sore throat.
      • 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.
      • Popkin D.L.
      • Zilka S.
      • Dimaano M.
      • et al.
      Cetylpyridinium chloride (CPC) exhibits potent, rapid activity against influenza viruses in vitro and in vivo.
      Hypotheses about a possible action over SARS-CoV-2 are based on its lysosomotropic mechanism of action and its ability to destroy viral capsids.
      • Baker N.
      • Williams A.J.
      • Tropsha A.
      • et al.
      Repurposing quaternary ammonium compounds as potential treatments for COVID-19.
      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.
      • Parhar H.S.
      • Tasche K.
      • Brody R.M.
      • et al.
      Topical preparations to reduce SARS-CoV-2 aerosolization in head and neck mucosal surgery.
      It is typically used in a 1% concentration
      • 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.
      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.

      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]

      • 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.
      Previously studies have shown that PVP-I has higher virucidal activity than other commonly used antiseptic agents, including CHX and benzalkonium chloride.
      • Kariwa H.
      • Fujii N.
      • Takashima I.
      Inactivation of SARS coronavirus by means of povidone-iodine, physical conditions and chemical reagents.
      It is safe, reporting a prevalence of 0.4% allergy cases,
      • Lachapelle J.M.
      Allergic contact dermatitis from povidone-iodine: a re-evaluation study.
      does not produce tooth or tongue discolouration or taste disturbances
      • Slots J.
      Selection of antimicrobial agents in periodontal therapy.
      and, unlike alcohol-based products, can be used when using electrocautery.
      • Shiraishi T.
      • Nakagawa Y.
      Evaluation of the bactericidal activity of povidone-iodine and commercially available gargle preparations.
      Its effectiveness has been well demonstrated through many in vitro studies against multiple viruses, including SARS-CoV, MERS-CoV, and influenza virus A (H1N1).
      • Parhar H.S.
      • Tasche K.
      • Brody R.M.
      • et al.
      Topical preparations to reduce SARS-CoV-2 aerosolization in head and neck mucosal surgery.
      • Kariwa H.
      • Fujii N.
      • Takashima I.
      Inactivation of SARS coronavirus by means of povidone-iodine, physical conditions and chemical reagents.
      • 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.
      Recent investigations have proposed that 0.23% PVP-I mouthwash for at least 15 seconds before procedures may reduce salivary viral load,
      • 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.
      indicating its use in COVID-19-positive patients.
      • Peng X.
      • Xu X.
      • Li Y.
      • et al.
      Transmission routes of 2019-nCoV and controls in dental practice.

      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]

      • 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.
      • Challacombe S.J.
      • Kirk-Bayley J.
      • Sunkaraneni V.S.
      • et al.
      Povidone iodine.

      Suggested recommendations

      Gently gargle for 30 seconds in the oral cavity and 30 seconds in the back of the throat with: 1.5%
      • American Dental Association
      ADA interim guidance for minimizing risk of COVID-19 transmission.
      or 3%
      • 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.
      H2O2 15 ml; PVP-I, 0.2%,
      • American Dental Association
      ADA interim guidance for minimizing risk of COVID-19 transmission.
      0.4%,
      • 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.
      or 0.5%
      • Challacombe S.J.
      • Kirk-Bayley J.
      • Sunkaraneni V.S.
      • et al.
      Povidone iodine.
      • 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.
      9 ml; 0.12% CHX 15 ml;
      • Yoon J.G.
      • Yoon J.
      • Song J.Y.
      • et al.
      Clinical significance of a high SARS-CoV-2 viral load in the saliva.
      or 0.05% CPC 15 ml.
      • 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.
      • Baker N.
      • Williams A.J.
      • Tropsha A.
      • et al.
      Repurposing quaternary ammonium compounds as potential treatments for COVID-19.

      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

        • 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
        • 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
        • 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 (e1): 1015-1026
        • 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
        • 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
        • 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
        • Li F.
        Structure, function, and evolution of coronavirus spike proteins.
        Annu Rev Virol. 2016; 3: 237-261
        • Chen Y.
        • Guo Y.
        • Pan Y.
        • et al.
        Structure analysis of the receptor binding of 2019-nCoV.
        Biochem Biophys Res Commun. 2020; 525: 135-140
        • 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
        • 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
        • 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
        • 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
        • Badran Z.
        • Gaudin A.
        • Struillou X.
        • et al.
        Periodontal pockets: a potential reservoir for SARS-CoV-2?.
        Med Hypoth. 2020; 143: 109907
        • 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 (S1806-83242016000100801)
        • Anschau V.
        • Sanjuán R.
        Fibrinogen gamma chain promotes aggregation of vesicular stomatitis virus in saliva.
        Viruses. 2020; 12: 282
        • Baghizadeh Fini M.
        Oral saliva and COVID-19.
        Oral Oncol. 2020; 108: 104821
        • American Dental Association
        ADA interim guidance for minimizing risk of COVID-19 transmission.
        2020 (Available from URL: https://www.kavo.com/en-us/resource-center/ada-interim-guidance-minimizing-risk-covid-19-transmission [last accessed 13.08.20])
      1. 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]

        • 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
        • Vitkov L.
        • Hermann A.
        • Krautgartner W.D.
        • et al.
        Chlorhexidine-induced ultrastructural alterations in oral biofilm.
        Microsc Res Tech. 2005; 68: 85-89
        • 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
        • 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
        • Fehr A.R.
        • Perlman S.
        Coronaviruses: an overview of their replication and pathogenesis.
        Methods Mol Biol. 2015; 1282: 1-23
        • 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
        • Marshall M.V.
        • Cancro L.P.
        • Fischman S.L.
        Hydrogen peroxide: a review of its use in dentistry.
        J Periodontol. 1995; 66: 786-796
        • Walsh L.J.
        Safety issues relating to the use of hydrogen peroxide in dentistry.
        Aust Dent J. 2000; 45: 257-289
        • 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
        • 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
        • Mentel R.
        • Shirrmakher R.
        • Kevich A.
        • et al.
        Virus inactivation by hydrogen peroxide.
        Vopr Virusol. 1977; ([in Russian]): 731-733
        • Gerba C.P.
        Quaternary ammonium biocides: efficacy in application.
        Appl Environ Microbiol. 2015; 81: 464-469
        • 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
        • 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
        • 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
        • 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
        • Baker N.
        • Williams A.J.
        • Tropsha A.
        • et al.
        Repurposing quaternary ammonium compounds as potential treatments for COVID-19.
        Pharm Res. 2020; 37: 104
        • 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
        • 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
      2. 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]

        • 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
        • Kariwa H.
        • Fujii N.
        • Takashima I.
        Inactivation of SARS coronavirus by means of povidone-iodine, physical conditions and chemical reagents.
        Dermatology. 2006; 212: 119-123
        • Lachapelle J.M.
        Allergic contact dermatitis from povidone-iodine: a re-evaluation study.
        Cont Dermat. 2005; 52: 9-10
        • Slots J.
        Selection of antimicrobial agents in periodontal therapy.
        J Periodontal Res. 2002; 37: 389-398
        • Shiraishi T.
        • Nakagawa Y.
        Evaluation of the bactericidal activity of povidone-iodine and commercially available gargle preparations.
        Dermatology. 2002; 204: 37-41
        • 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
        • 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
        • Challacombe S.J.
        • Kirk-Bayley J.
        • Sunkaraneni V.S.
        • et al.
        Povidone iodine.
        Br Dent J. 2020; 228: 656-657
        • 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
        • 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