dgkh000395 10.3205/dgkh000395 urn:nbn:de:0183-dgkh0003952 Letter to the Editor Vilhena Vilhena Fabiano Vieira FV

TRIALS – Oral Health & Technologies, Bauru, São Paulo, Brazil

author Brito Reia Brito Reia Verônica Caroline VC

Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil

author da Fonseca Orcina da Fonseca Orcina Bernardo B

Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil

author Santos Santos Caíque Andrade CA

Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil

author Zangrando Zangrando Mariana M

Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil

author Cardoso de Oliveira Cardoso de Oliveira Rodrigo R

Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil

author da Silva Santos da Silva Santos Paulo Sérgio PS

Bauru Dental School, University of São Paulo, Alameda Octávio Pinheiro Brisolla 9-75, Vila Universitária, Bauru, São Paulo 17012-901, Brazil, Phone +55 14 3226-6116Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil

paulosss@fob.usp.br author German Medical Science GMS Publishing House

Düsseldorf

610 20210709 engl This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). 2196-5226 16 GMS Hygiene and Infection Control GMS Hyg Infect Control 24 CAPES Letter to the editorVaccines and other drugs have been developed and delivered to fight SARS-CoV-2. Successful measures to prevent infection with the virus, such as wearing masks, attention to hygiene and social distancing in conjunction with antiviral mouthwashes, have been recommended to the population for daily use during the COVID-19 pandemic , .Scientific evidence has shown the presence of viruses in oral structures and indications for antiviral oral antiseptics have been investigated. Thus, in vitro studies with mouthwashes against coronavirus published during the pandemic seemed promising . However, until September 2020 there was no clinical or laboratorial evidence for their indication, since only few studies had been published . In March 2021 (Ather et al. 2021 ), based on the available evidence. It was demonstrated that the use of antiviral oral antiseptics (mouthrinses) had the potential to reduce the in vitro viral load of SARS-CoV-2, but the in vivo effectiveness was still inconclusive . Only in April 2021 was it suggested that there was sufficient in vitro and in vivo evidence of the effectiveness of some oral antiseptics in inactivating SARS-CoV-2 and other coronaviruses (Figure 1 ).Our research group reinforces the claims for the potential of antiviral mouthwashes to combat COVID-19. Recently, an in vitro evaluation of the virucidal activity of a mouthwash containing antiviral phthalocyanine derivative (APD), a substance that can promote reactive oxygen species generation or redox processes , was conducted according to the TCID50 methodology (Median Tissue Culture Infectious Dose). The periods of 30 seconds, 1 minute, and 5 minutes were observed, reaching a percentage of viral inactivation above 99.9% of the SARS-CoV-2 viral load, as shown in Table 1 . This research was approved by Human Research Ethics Committee (CAAE 34070620.6.0000.5417) of the institution that performed the research.This is another relevant result of the positive action of APD, since a reduction in the viral load of SARS-CoV-2 above 90% has already been demonstrated in previous in vitro studies , , as well as the rapid clinical improvement of COVID-19 symptoms . In a randomized study conducted in a hospital environment, COVID-19 patients with mild and moderate cases underwent an adjuvant APD mouthwash protocol. The APD mouthwash group, with a maximum of 7 days of symptoms associated with conventional treatment for COVID-19, was discharged sooner (4 days median). This group also presented lower disease severity (without intensive care unit [ICU] or deaths) when compared to the non-APD mouthwash group (7 days median, 28.6% ICU, 14.3% mortality rate) .In short, the prospect of a low-cost, hygienic personal-care method, suggestive of good option such as the use of antiviral oral antiseptic, may be an important strategy for reducing the impact of COVID-19. NotesCompeting interestsAll authors submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Vilhena reports personal fees from TRIALS Inc while conducting the study. In addition, Dr. Vilhena has a patent pending. Dr. DA Silva Santos reports grants from CNPq process nº. 309525/2018-7. The other authors claim no conflicts of interestFundingThis study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil (Finance Code 001).AcknowledgmentsCROP Biotechnology for the experimental design and execution. Kramer A Eggers M Hübner NO Walger P Steinmann E Exner M Virucidal gargling and virucidal nasal spray 2021 GMS Hyg Infect Control Doc02 Kramer A, Eggers M, Hübner NO, Walger P, Steinmann E, Exner M. Virucidal gargling and virucidal nasal spray. GMS Hyg Infect Control. 2021 Jan 18;16:Doc02. DOI: 10.3205/dgkh000373 https://doi.org/10.3205/dgkh000373 da Silva Santos PS da Fonseca Orcina B da Costa Alves LM Cardoso de Oliveira R Mariana Schutzer Ragghianti Zangrando M Vieira Vilhena F A Recommendation of PHTALOX® Mouthwash for Preventing Infection and Progression of COVID-19 2020 Acta Scient Dent Sci 111-2 da Silva Santos PS, da Fonseca Orcina B, da Costa Alves LM, Cardoso de Oliveira R, Mariana Schutzer Ragghianti Zangrando M, Vieira Vilhena F. A Recommendation of PHTALOX® Mouthwash for Preventing Infection and Progression of COVID-19. Acta Scient Dent Sci. 2020;4(12):111-2. DOI: 10.31080/ASDS.2020.04.0991 https://doi.org/10.31080/ASDS.2020.04.0991 Meister TL Brüggemann Y Todt D Conzelmann C Müller JA Groß R Münch J Krawczyk A Steinmann J Steinmann J Pfaender S Steinmann E Virucidal Efficacy of Different Oral Rinses Against Severe Acute Respiratory Syndrome Coronavirus 2 2020 J Infect Dis 1289-92 Meister TL, Brüggemann Y, Todt D, Conzelmann C, Müller JA, Groß R, Münch J, Krawczyk A, Steinmann J, Steinmann J, Pfaender S, Steinmann E. Virucidal Efficacy of Different Oral Rinses Against Severe Acute Respiratory Syndrome Coronavirus 2. J Infect Dis. 2020 09;222(8):1289-92. DOI: 10.1093/infdis/jiaa471 https://doi.org/10.1093/infdis/jiaa471 Carrouel F Gonçalves LS Conte MP Campus G Fisher J Fraticelli L Gadea-Deschamps E Ottolenghi L Bourgeois D Antiviral Activity of Reagents in Mouth Rinses against SARS-CoV-2 2021 J Dent Res 124-32 Carrouel F, Gonçalves LS, Conte MP, Campus G, Fisher J, Fraticelli L, Gadea-Deschamps E, Ottolenghi L, Bourgeois D. Antiviral Activity of Reagents in Mouth Rinses against SARS-CoV-2. J Dent Res. 2021 Feb;100(2):124-32. DOI: 10.1177/0022034520967933 https://doi.org/10.1177/0022034520967933 Ather A Parolia A Ruparel NB Efficacy of Mouth Rinses Against SARS-CoV-2: A Scoping Review 2021 Front Dent Med 648547 Ather A, Parolia A, Ruparel NB. Efficacy of Mouth Rinses Against SARS-CoV-2: A Scoping Review. Front Dent Med. 2021;2:648547. DOI: 10.3389/fdmed.2021.648547 https://doi.org/10.3389/fdmed.2021.648547 Mateos-Moreno MV Mira A Ausina-Márquez V Ferrer MD Oral antiseptics against coronavirus: in-vitro and clinical evidence 2021 J Hosp Infect 30-43 Mateos-Moreno MV, Mira A, Ausina-Márquez V, Ferrer MD. Oral antiseptics against coronavirus: in-vitro and clinical evidence. J Hosp Infect. 2021 Jul;113:30-43. DOI: 10.1016/j.jhin.2021.04.004 https://doi.org/10.1016/j.jhin.2021.04.004 Teodoro G Santos C Carvalho M Koga-Ito C Khouri S Vilhena F PHTALOX® Antimicrobial Action and Cytotoxicity: in vitro Study 2020 J Dent Res 0839 Teodoro G, Santos C, Carvalho M, Koga-Ito C, Khouri S, Vilhena F. PHTALOX® Antimicrobial Action and Cytotoxicity: in vitro Study. J Dent Res.2020;99(Spec. Iss. A):0839. Available frrom: https://iadr.abstractarchives.com/abstract/20iags-3314903/phtalox-antimicrobial-action-and-cytotoxicity-in-vitro-study https://iadr.abstractarchives.com/abstract/20iags-3314903/phtalox-antimicrobial-action-and-cytotoxicity-in-vitro-study Santos PSS Orcina BF Machado RRG Beneficial effects of a mouthwash containing an antiviral phthalocyanine derivative on the length of hospital stay for COVID-19 [Preprint] 2021 Research Square Santos PSS, Orcina BF, Machado RRG, et al. Beneficial effects of a mouthwash containing an antiviral phthalocyanine derivative on the length of hospital stay for COVID-19 [Preprint]. Research Square. 2021 Mar 16. DOI: 10.21203/rs.3.rs-330173/v1 https://doi.org/10.21203/rs.3.rs-330173/v1 Santos C da Fonseca Orcina B Brito Reia VC Ribeiro LG Grotto RMT Prudenciatti A de Moraes LN Ragghianti Zangrando M Vilhena FV da Silva Santos PS Virucidal Activity of the Antiseptic Mouthwash and Dental Gel Containing Anionic Phthalocyanine Derivative: In vitro Study 2021 Clin Cosmet Investig Dent 269-74 Santos C, da Fonseca Orcina B, Brito Reia VC, Ribeiro LG, Grotto RMT, Prudenciatti A, de Moraes LN, Ragghianti Zangrando M, Vilhena FV, da Silva Santos PS. Virucidal Activity of the Antiseptic Mouthwash and Dental Gel Containing Anionic Phthalocyanine Derivative: In vitro Study. Clin Cosmet Investig Dent. 2021;13:269-74. DOI: 10.2147/CCIDE.S315419 https://doi.org/10.2147/CCIDE.S315419 da Fonseca Orcina B Vilhena FV Cardoso de Oliveira R Marques da Costa Alves L Araki K Toma SH Ragghianti Zangrando MS da Silva Santos PS A Phthalocyanine Derivate Mouthwash to Gargling/Rinsing as an Option to Reduce Clinical Symptoms of COVID-19: Case Series 2021 Clin Cosmet Investig Dent 47-50 da Fonseca Orcina B, Vilhena FV, Cardoso de Oliveira R, Marques da Costa Alves L, Araki K, Toma SH, Ragghianti Zangrando MS, da Silva Santos PS. A Phthalocyanine Derivate Mouthwash to Gargling/Rinsing as an Option to Reduce Clinical Symptoms of COVID-19: Case Series. Clin Cosmet Investig Dent. 2021;13:47-50. DOI: 10.2147/CCIDE.S295423 https://doi.org/10.2147/CCIDE.S295423 11

Table 1: Percentage of viral inactivation of APD Mouthwash

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1 1 Figure 1: Timeline of scientific evidence for antiviral mouthwash recommendation against SARS-CoV-2

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