key: cord-0741989-m2drezws authors: Vergara-Buenaventura, Andrea; Castro-Ruiz, Carmen title: The Use of Mouthwashes against COVID-19 in Dentistry date: 2020-08-15 journal: Br J Oral Maxillofac Surg DOI: 10.1016/j.bjoms.2020.08.016 sha: b7f1cddcbebc2a0567aa495355db909ac03d6681 doc_id: 741989 cord_uid: m2drezws 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 it uses can prevent the transmission of SARS-CoV-2, preoperational 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. Thus, this article aims to provide a comprehensive review of the current recommendations on the use of mouthwashes against COVID – 19 pandemic and to analyze the advantages and disadvantages of most conventional antiseptic mouthwashes used in dentistry. Antiseptic mouthwashes have been widely used as a standard measure before routine dental treatment, especially before surgery. [1, 2] It plays 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. Thus, this article aims to provide a comprehensive review of the current recommendations on the use of mouthwashes against COVID-19 pandemic and to analyze the advantages and disadvantages of most conventional antiseptic mouthwashes used in dentistry. 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 Angiotensinconverting enzyme 2 (ACE2) receptors is responsible for the entrance 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 of ACE2 is found in different tissue cells, including mucosal tissues, gingiva, non-keratinizing squamous epithelium, in epithelial cells of the tongue and salivary glands. [8, 11] Moreover, high SARS-CoV-2 viral load has been detected in saliva samples [6, 12] , and it has even been suggested its presence in periodontal pockets. [13] These findings agree with previous investigations that have suggested that virus transmission can be closely connected with saliva interactions [14, 15] making oral tissues a possible reservoir from which SARS-CoV-2 transmission may occur during coughing, sneezing, talking, and even during dental care. [1, 12, 16] J o u r n a l P r e -p r o o f 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 [1, 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. 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 as influenza A, parainfluenza, herpesvirus 1, cytomegalovirus, and hepatitis B. [22] Although COVID-19 is an enveloped virus, 0.12% CHX gluconate was suggested to have less or no effect against coronaviruses when compared to other mouthwashes. [1, 23, 24] However, Yoon et al. [6] found SARS-CoV-2 suppression for 2 hours after using 15ml 0.12% CHX once, suggesting that its use would be beneficial for the control of COVID-19 transmission. H2O2 has been used in dentistry alone or combined with salts since the start of the century. [25] As a mouthwash, H2O2 is an odourless, clear, and colourless liquid. [26] Lack of adverse soft tissue J o u r n a l P r e -p r o o f effect was found in many studies of 1% to 1.5% H2O2 used as a daily rinse over two years followup. [27, 28] An in vitro study found that 3% H2O2 within 1 to 30 minutes 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 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] 0.05% CPC has been used to reduce dental plaque and gingivitis [32] 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. Povidone-iodine (PVP-I) is a water-soluble iodine complex that has been widely used as a presurgical skin antiseptic and as a mouthwash. [36] It is typically used in a 1% concentration [37] 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 oxidizes nucleic acid structures J o u r n a l P r e -p r o o f 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/tongue discolouration or taste disturbances [42] 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 saliva viral load [44] , indicating its use in COVID-19 positive patients. [4, 38, 45, 46] Gently gargles for 30 seconds in the oral cavity and 30 seconds in the back of the throat with:  15ml H2O2 at 1.5% [17] Error! Bookmark not defined. or 3% [47]  9ml of PVP-I at 0.2%Error! Bookmark not defined. , 0.4Error! Bookmark not defined. or 0.5% [46, 48]  15ml of CHX at 0.12% [6]  15ml of CPC at 0.05% [31, 35] With the limitations of this brief review and despite little clinical evidence, the authors conclude to suggest the use of preprocedural mouthwashes in dental practice to reduce SARS-CoV-2 viral load previous dental procedures and to reduce the cross-infection risk while treating patients during the pandemic. Clinical studies, including control subjects and at large-scale, are required to Preoperative antiseptics in clean/contaminated maxillofacial and oral surgery: prospective randomized study A prospective observational study on perioperative use of antibacterial agents in implant surgery Efficacy of preprocedural mouthrinses in the reduction of microorganisms in aerosol: A systematic review Transmission routes of 2019-nCoV and controls in dental practice COVID-19): Implications for Clinical Dental Care Clinical Significance of a High SARS-CoV-2 Viral Load in the Saliva Structure, Function, and Evolution of Coronavirus Spike Proteins Structure analysis of the receptor binding of 2019-nCoV High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis Saliva is a non-negligible factor in the spread of COVID-19 Periodontal pockets: A potential reservoir for SARS-CoV-2? Zika virus infection spread through saliva--a truth or myth? Fibrinogen Gamma Chain Promotes Aggregation of Vesicular Stomatitis Virus in Saliva Oral saliva and COVID-19 American Dental Association. ADA Interim Guidance for Minimizing Risk of COVID-19 Center for Disease Control and Prevention. Interim Infection Prevention and Control Guidance for Dental Settings During the COVID-19 Response Chlorhexidine: expanding the armamentarium for infection control and prevention Chlorhexidine-induced ultrastructural alterations in oral biofilm Chlorhexidine mouthwash as an adjunct to mechanical therapy in chronic periodontitis: A meta-analysis In vitro virucidal effectiveness of a 0.12%-chlorhexidine gluconate mouthrinse Coronaviruses: an overview of their replication and pathogenesis Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents Hydrogen peroxide: a review of its use in dentistry Safety issues relating to the use of hydrogen peroxide in dentistry Microbiological and clinical effects of topical subgingival antimicrobial treatment on human periodontal disease Microbiological and clinical effects of chlorhexidine digluconate and hydrogen peroxide mouthrinses on developing plaque and gingivitis Inaktivatsiia virusov perekis'iu vodoroda Quaternary ammonium biocides: efficacy in application 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 A clinical investigation of the efficacy of a commercial mouthrinse containing 0.05% cetylpyridinium chloride to control established dental plaque and gingivitis The effectiveness of a preprocedural mouthrinse containing cetylpyridinium chloride in reducing bacteria in the dental office Cetylpyridinium Chloride (CPC) Exhibits Potent, Rapid Activity Against Influenza Viruses in vitro and in vivo Repurposing Quaternary Ammonium Compounds as Potential Treatments for COVID-19 Topical preparations to reduce SARS-CoV-2 aerosolization in head and neck mucosal surgery Effect of mouth rinsing with two polyvinylpyrrolidoneiodine mixtures on iodine absorption and thyroid function The Use of Povidone Iodine Nasal Spray and Mouthwash During the Current COVID-19 Pandemic May Reduce Cross Infection and Protect Healthcare Workers Topical povidone iodine inhibits bacterial growth in the oral cavity of patients on mechanical ventilation: a randomized controlled study Inactivation of SARS coronavirus by means of povidone-iodine, physical conditions and chemical reagents Allergic contact dermatitis from povidone-iodine: A re-evaluation study Selection of antimicrobial agents in periodontal therapy Evaluation of the bactericidal activity of povidone-iodine and commercially available gargle preparations In Vitro Bactericidal and Virucidal Efficacy of Povidone-Iodine Gargle/Mouthwash Against Respiratory and Oral Tract Pathogens 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 Povidone iodine Hydrogen peroxide and viral infections: A literature of print Rapid In-Vitro Inactivation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Using Povidone-Iodine Oral Antiseptic Rinse