Main Article Content

Authors

Aim: The aim of this randomised, double-blind, placebo-controlled pilot clinical trial is to evaluate the capacity of a mouthwash to reduce SARS-CoV-2 viral load in the saliva of patients with COVID-19.


Methods: Twenty-three symptomatic SARS-CoV-2-positive outpatients were selected and randomised into two groups  and registered at NTC 04563689. Both groups rinsed and gargled for one minute with either distilled water (Placebo) or with 0.05% Cetylpyridinium chloride (CPC) plus 0.12% Chlorhexidine (CHX) mouthwash (PERIOAID Intensive CareÒ). Saliva samples were collected before the use of placebo or mouthwash and after 15 minutes and 1 and 2 hours of either of the above treatment. A saliva sample was also taken five days after regular use of placebo or mouthwash twice daily. The virus was detected by qRT-PCR.


Results: A great heterogeneity in the viral load values was observed at baseline in both groups for nasopharyngeal and saliva samples. Most of the patients who used the mouthwash (8/12) had a significant decrease in baseline viral load after 15 min (greater than 99% reduction). This inhibitory effect was maintained for up to two hours in 10 of the 12 patients. At five days, SARS-CoV-2 RNA was detected in only 1 patient from the mouthwash group and in 5 from the placebo group.


Conclusions: This study points out that a CPC mouthwash can reduce the viral load in saliva of COVID-positive patients. This finding may be important in transmission control of SARS-CoV-2. Nevertheless, the clinical relevance of CPC mouthwash-reduction on SARS-CoV-2 shedding in saliva requires further study

Adolfo Contreras Renjifo, Universidad del Valle, Facultad de Salud, Escuela de Odontología, Director Grupo de Medicina Periodontal

Universidad del Valle, Facultad de Salud, Escuela de Odontología, Director Grupo de Medicina Periodontal

Rubén León Berrios, Department of Microbiology

Department of Microbiology, Dentaid Research Center, Cerdanyola del Vallès, Spain

Andrés Castillo Giraldo, Department Biology, University of Valle, Cali, Colombia.

Department Biology, University of Valle, Cali, Colombia.

José Luis Bahamon, Department of Microbiology, University of Valle, Cali, Colombia. In representation of the Covid-19 Team at Universidad del Valle, Cali, Colombia.

Department of Microbiology, University of Valle, Cali, Colombia. In representation of the Covid-19 Team at Universidad del Valle, Cali, Colombia.

Yurani Giraldo, Red de Salud del Centro ESE, Cali, Colombia.

Red de Salud del Centro ESE, Cali, Colombia.

Gerardo Andrés Libreros Zúñiga, Department of Microbiology, University of Valle, Cali, Colombia. In representation of the Covid-19 Team at Universidad del Valle, Cali, Colombia.

Department of Microbiology, University of Valle, Cali, Colombia. In representation of the Covid-19 Team at Universidad del Valle, Cali, Colombia.

Alejandro Contreras Parra, Dental School, Periodontal Research Group, University of Valle, Cali, Colombia

Dental School, Periodontal Research Group, University of Valle, Cali, Colombia

Juan Gispert, Department of Microbiology, Dentaid Research Center, Cerdanyola del Vallès, Spain

Department of Microbiology, Dentaid Research Center, Cerdanyola del Vallès, Spain

Julián Balanta- Melo, Dental School, Periodontal Research Group, University of Valle, Cali, Colombia. Evidence-Based Practice Unit, Faculty of Health, Universidad del Valle/Hospital Universitario del Valle Evaristo García, Cali, Colombia

Dental School, Periodontal Research Group, University of Valle, Cali, Colombia

Evidence-Based Practice Unit, Faculty of Health, Universidad del Valle/Hospital Universitario del Valle Evaristo García, Cali, Colombia

Fausto Andrés Alban, Universidad del Valle, Faculty of Health, School of Medicine, Cali, Colombia.

Universidad del Valle, Faculty of Health, School of Medicine, Cali, Colombia.

Beatriz Parra, University of Valle

University of Valle, Department of Microbiology, Cali, Colombia. In representation of the Covid-19 Team at Universidad del Valle, Cali, Colombia.

Contreras Renjifo, A., León Berrios, R., Castillo Giraldo, A., Bahamon, J. L., Giraldo, Y., Libreros Zúñiga, G. A., Contreras Parra, A., Gispert, J., Balanta- Melo, J., Alban, F. A., & Parra, B. (2023). A Mouthwash with Cetylpyridinium Chloride Is Reducing Salivary SARS-CoV-2 Viral Load in +COVID-19. Revista Estomatología, 31(1). https://doi.org/10.25100/re.v31i1.12669

WHO. Coronavirus disease (COVID‐19) situation reports. (2019). https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports.

Chau NVV, Thanh Lam V, Thanh Dung N, Yen LM, Minh NNQ, Hung LM, et al. The natural history and transmission potential of asymptomatic SARS-CoV-2 infection. Clin Infect Dis. 2020; 71(10), 2679–2687.

To K, Tsang O, Yip C, Chan K, Wu T, Chan J, et al. Consistent detection of 2019 novel coronavirus in saliva. Clin Infect Dis. 2020; 71(15), 841–843. DOI: https://doi.org/10.1093/cid/ciaa149

Walsh KA, Jordan K, Clyne B, Rohde D, Drummond L, Byrne P, et al. SARS-CoV-2 detection, viral load and infectivity over the course of an infection. J Infect. 2020; 81(3): 357–371. DOI: https://doi.org/10.1016/j.jinf.2020.06.067

Zhu J, Guo J, Xu Y, Chen X. Viral dynamics of SARS-CoV-2 in saliva from infected patients. J Infect. 2020; 81(3): e48-e50. DOI: https://doi.org/10.1016/j.jinf.2020.06.059

He Z, Zhao C, Dong Q, Zhuang H, Song S, Peng G, Dwyer DE. Effects of severe acute respiratory syndrome (SARS) coronavirus infection on peripheral blood lymphocytes and their subsets. Int J Infect Dis. 2005; 9(6): 323-30. DOI: https://doi.org/10.1016/j.ijid.2004.07.014

Huang LS, Li L, Dunn L, He M. Taking account of asymptomatic infections: A modeling study of the COVID-19 outbreak on the Diamond Princess cruise ship. PLoS One. 2021; 16(3): e0248273. DOI: https://doi.org/10.1371/journal.pone.0248273

Ferretti L, Wymant C, Kendall M, et al. Quantifying SARS-CoV-2 transmission suggests epidemic control with digital contact tracing. Science. 2020; 368(6491): eabb6936. DOI: https://doi.org/10.1126/science.abb6936

Burton M, Clarkson J, Goulao B, Glenny AM, McBain A, Schilder A, et al. Antimicrobial mouthwashes (gargling) and nasal sprays administered to patients with suspected or confirmed COVID-19 infection to improve patient outcomes and to protect healthcare workers treating them. Cochrane Database Syst Rev. 2020; 9:CD013627. DOI: https://doi.org/10.1002/14651858.CD013627.pub2

Herrera D, Serrano J, Roldán S, Sanz M. Is the oral cavity relevant in SARS-CoV-2 pandemic? Clin Oral Investig. 2020; 24(8): 2925-2930. DOI: https://doi.org/10.1007/s00784-020-03413-2

O'Donnell VB, Thomas D, Stanton R, Maillard J-Y, Murphy R, Jones S, et al. Potential Role of Oral Rinses Targeting the Viral Lipid Envelope in SARS-CoV-2 Infection. Function (Oxf). 2020; 1(1): zqaa002. DOI: https://doi.org/10.1093/function/zqaa002

Popkin D, Zilka S, Dimaano M, Fujioka H, Rackley C, Salata R, et al. Cetylpyridinium Chloride (CPC) Exhibits Potent, Rapid Activity Against Influenza Viruses in vitro and in vivo. Pathog Immun. 2017; 2(2): 252-269. DOI: https://doi.org/10.20411/pai.v2i2.200

Shen L, Niu J, Wang C, Huang B, Wang W, Zhu N, et al. High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses. J Virol. 2019; 93(12):e00023-19. DOI: https://doi.org/10.1128/JVI.00023-19

Lu X, Wang L, Sakthivel S, Whitaker B, Murray J, Kamili S et al. US CDC Real-Time Reverse Transcription PCR Panel for Detection of Severe Acute Respiratory Syndrome Coronavirus 2. Emerg Infect Dis. 2020; 26(8):1654–1665. DOI: https://doi.org/10.3201/eid2608.201246

Mukherjee PK, Esper F, Buchheit K, Arters K, Adkins I, Ghannoum M, 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(1): 74. DOI: https://doi.org/10.1186/s12879-016-2177-8

Ellinger B, Bojkova D, Zaliani A, Cinati J, Claussen C, Westhaus S, et al. A SARS-CoV-2 cytopathicity dataset generated by high-content screening of a large drug repurposing collection. Sci Data. 2021; 8(1): 70. DOI: https://doi.org/10.1038/s41597-021-00848-4

Komine A, Yamaguchi E, Okamoto N, Yamamoto K. Virucidal activity of oral care products against SARS-CoV-2 in vitro. J Oral Maxillofac Surg Med Pathol. 2021; 10.1016/j.ajoms.2021.02.002. DOI: https://doi.org/10.1016/j.ajoms.2021.02.002

Meister T, Brüggemann Y, Todt D, Conzelmann C, Müller J, Groß R, et al. Virucidal Efficacy of Different Oral Rinses Against Severe Acute Respiratory Syndrome Coronavirus 2. J Infect Dis. 2020; 222(8):1289-1292. DOI: https://doi.org/10.1093/infdis/jiaa471

Koch-Heier J, Hoffmann H, Schindler M, Lussi A, Planz O. Inactivation of SARS-CoV-2 through Treatment with the Mouth Rinsing Solutions ViruProX® and BacterX® Pro. Microorganisms. 2021; 9(3):521. DOI: https://doi.org/10.3390/microorganisms9030521

Davies K, Buczkowski H, Welch SR, et al. Effective in vitro inactivation of SARS-CoV-2 by commercially available mouthwashes. J Gen Virol. 2021;102(4):10. 1099/jgv.0.001578. DOI: https://doi.org/10.1099/jgv.0.001578

Jain A, Grover V, Singh C, Sharma A, Das DK, Singh P, et al. Chlorhexidine: An effective anticovid mouth rinse. J Indian Soc Periodontol. 2021; 25(1):86-88. DOI: https://doi.org/10.4103/jisp.jisp_824_20

Anderson DE, Sivalingam V, Kang AEZ, Ananthanarayanan A, Arumugam H, Jenkins TM, et al. Povidone-Iodine Demonstrates Rapid in vitro Virucidal Activity Against SARS-CoV-2, The Virus Causing COVID-19 Disease. Infect Dis Ther. 2020; 9(3): 669-675. DOI: https://doi.org/10.1007/s40121-020-00316-3

Bidra AS, Pelletier JS, Westover JB, Frank S, Brown SM, Tessema B. Comparison of in vitro Inactivation of SARS CoV-2 with Hydrogen Peroxide and Povidone-Iodine Oral Antiseptic Rinses. J Prosthodont. 2020; 29(7): 599-603. DOI: https://doi.org/10.1111/jopr.13220

Gottsauner MJ, Michaelides I, Schmidt B, Scholz K, Buchalla W, Widbiller M, et al. A prospective clinical pilot study on the effects of a hydrogen peroxide mouthrinse on the intraoral viral load of SARS-CoV-2. Clin Oral Investig. 2020; 24(10): 3707-3713. DOI: https://doi.org/10.1007/s00784-020-03549-1

Martínez-Lamas L, Diz P, Pérez MT, Del Campo V, Cabrera JJ, López AM, et al. Is povidone iodine mouthwash effective against SARS-CoV-2? First in vivo tests. Oral Dis. 2020; 10.1111/odi.13526. DOI: https://doi.org/10.1111/odi.13526

Seneviratne C J, Balan P, Ko K, Udawatte N S, Lai D, Ng D, et al. Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore. Infection. 2021; 49(2): 305-311. DOI: https://doi.org/10.1007/s15010-020-01563-9

Amirian ES. Potential fecal transmission of SARS-CoV-2: Current evidence and implications for public health. Int J Infect Dis. 2020; 95:363-370. DOI: https://doi.org/10.1016/j.ijid.2020.04.057

Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020; 581(7809): 465-469. DOI: https://doi.org/10.1038/s41586-020-2196-x

Wang XW, Li J, Guo T, Zhen B, Kong Q, Yi B, et al. Concentration and detection of SARS coronavirus in sewage from Xiao Tang Shan Hospital and the 309th Hospital of the Chinese People's Liberation Army. Water Sci Technol. 2005;52(8):213-221. DOI: https://doi.org/10.2166/wst.2005.0266

Alexandersen S, Chamings A, Bhatta TR. SARS-CoV-2 genomic and subgenomic RNAs in diagnostic samples are not an indicator of active replication. Nat Commun. 2020;11(1):6059. DOI: https://doi.org/10.1038/s41467-020-19883-7

Received 2022-12-09
Accepted 2023-03-07
Published 2023-01-23