Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore
Chaminda J Seneviratne, Preethi Balan, Kwan Ki Karrie Ko, Nadeeka S Udawatte, Deborah Lai, Dorothy Hui Lin Ng, Indumathi Venkatachalam, Kheng Sit Lim, Moi Lin Ling, Lynette Oon, Bee Tin Goh, Xiang Ying Jean Sim
Infection, doi:10.1007/s15010-020-01563-9
Purpose One of the key approaches to minimize the risk of COVID-19 transmission would be to reduce the titres of SARS-CoV-2 in the saliva of infected COVID-19 patients. This is particularly important in high-risk procedures like dental treatment. The present randomized control trial evaluated the efficacy of three commercial mouth-rinse viz. povidone-iodine (PI), chlorhexidine gluconate (CHX) and cetylpyridinium chloride (CPC), in reducing the salivary SARS-CoV-2 viral load in COVID-19 patients compared with water. Methods A total of 36 SARS-CoV-2-positive patients were recruited, of which 16 patients were randomly assigned to four groups-PI group (n = 4), CHX group (n = 6), CPC group (n = 4) and water as control group (n = 2). Saliva samples were collected from all patients at baseline and at 5 min, 3 h and 6 h post-application of mouth-rinses/water. The samples were subjected to SARS-CoV-2 RT-PCR analysis. Results Comparison of salivary Ct values of patients within each group of PI, CHX, CPC and water at 5 min, 3 h and 6 h time points did not show any significant differences. However, when the Ct value fold change of each of the mouth-rinse group patients were compared with the fold change of water group patients at the respective time points, a significant increase was observed in the CPC group patients at 5 min and 6 h and in the PI group patients at 6 h.
Conclusion The effect of decreasing salivary load with CPC and PI mouth-rinsing was observed to be sustained at 6 h time point. Within the limitation of the current study, as number of the samples analyzed, the use of CPC and PI formulated that commercial mouth-rinses may be useful as a pre-procedural rinse to help reduce the transmission of COVID-19. ISRCTN (ISRCTN95933274), 09/09/20, retrospectively registered
Author contributions CJS, PB, KKKK, and JSXY contributed to conception, design, data acquisition and interpretation, drafted and critically revised the manuscript. NU, DL, DNHL, IV and GBT contributed to design and data acquisition, drafted and critically revised the manuscript. JLKS, LML, and LO contributed to data acquisition and interpretation, drafted and critically revised the manuscript. All the authors read and approved the final manuscript.
References
Alexander, Gorbalenya, Baric, De Groot, Drosten et al., The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2, Nat microbiol,
doi:10.1038/s41564-020-0695-zBernstein, Schiff, Echler, Prince, Feller et al., In vitro virucidal effectiveness of a 0.12%-chlorhexidine gluconate mouthrinse, J Dent Res,
doi:10.1177/00220345900690030901Cdc, Interim infection prevention and control guidance for dental settings during the coronavirus disease 2019 (COVID-19) pandemic
Chu, Pan, Cheng, Hui, Krishnan et al., Molecular diagnosis of a novel coronavirus (2019-nCoV) causing an outbreak of pneumonia, Clin Chem,
doi:10.1093/clinchem/hvaa029Ge, Yang, Xia, Fu, Zhang, Possible aerosol transmission of COVID-19 and special precautions in dentistry, J Zhejiang Univ Sci B,
doi:10.1631/jzus.B2010010Izzetti, Nisi, Gabriele, Graziani, COVID-19 transmission in dental practice: brief review of preventive measures in Italy, J Dent Res,
doi:10.1177/0022034520920580Kawana, Kitamura, Nakagomi, Matsumoto, Arita et al., Inactivation of human viruses by povidoneiodine in comparison with other antiseptics, Dermatology,
doi:10.1159/000246027Lamas, Dios, Rodríguez, Campo, Alvargonzalez et al., Is povidone iodine mouthwash effective against SARS-CoV-2? First in vivo tests Oral Dis,
doi:10.1111/odi.13526Liu, Wei, Alvarez, Wang, Du et al., Epithelial cells lining salivary gland ducts are early target cells of severe acute respiratory syndrome coronavirus infection in the upper respiratory tracts of rhesus macaques, J Virol,
doi:10.1128/JVI.02292-10Lu, These are the occupations with the highest COVID-19 risk, World Economic Forum
Meiller, Silva, Ferreira, Jabra-Rizk, Kelley et al., Efficacy of listerine antiseptic in reducing viral contamination of saliva, J Clin Periodontol,
doi:10.1111/j.1600-051X.2005.00673.xMeister, Brüggemann, Todt, Conzelmann, Müller et al., Virucidal efficacy of different oral rinses against severe acute respiratory syndrome coronavirus 2, J Infect Dis,
doi:10.1093/infdis/jiaa471Meng, Hua, Bian, Coronavirus Disease 2019 (COVID-19): emerging and future challenges for dental and oral medicine, J Dent Res,
doi:10.1177/0022034520914246Mukherjee, Esper, Buchheit, Arters, Adkins et al., Randomized, double-blind, placebo-controlled clinical trial to assess the safety and effectiveness of a novel dualaction oral topical formulation against upper respiratory infections, BMC Infect Dis,
doi:10.1186/s12879-016-2177-8O'donnell, Thomas, Stanton, Maillard, Murphy et al., Potential role of oral rinses targeting the viral lipid envelope in SARS-CoV-2 infection, Function,
doi:10.1093/function/zqaa002Ott, Strine, Watkins, Boot, Kalinich et al., Simply saliva: stability of SARS-CoV-2 detection negates the need for expensive collection devices, The Preprint Server For Health Sci,
doi:10.1101/2020.08.03.20165233Peng, Xu, Li, Cheng, Zhou et al., Transmission routes of 2019-nCoV and controls in dental practice, Int J Oral Sci,
doi:10.1038/s41368-020-0075-9Popkin, Zilka, Dimaano, Fujioka, Rackley et al., Cetylpyridinium chloride (CPC) exhibits potent, rapid activity against influenza viruses in vitro and in vivo, Pathog Immun,
doi:10.20411/pai.v2i2.200Rao, Manissero, Steele, Pareja, A systematic review of the clinical utility of cycle threshold values in the context of COVID-19, Infect Dis The,
doi:10.1007/s40121-020-00324-3To, Tsang, Chik-Yan Yip, Chan, Wu et al., Consistent detection of 2019 novel coronavirus in saliva, Clin Infect Dis,
doi:10.1093/cid/ciaa149Tu, Benn, RRApp, a robust randomization app, for clinical and translational research, J Clin Transl Sci,
doi:10.1017/cts.2017.310Worldometer, Coronavirus Cases
Wyllie, Fournier, Casanovas-Massana, Campbell, Tokuyama et al., Saliva or nasopharyngeal swab specimens for detection of SARS-CoV-2, N Engl J Med,
doi:10.1056/NEJMc2016359Xu, Zhong, Deng, Peng, Dan et al., High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa, Int J Oral Sci,
doi:10.1038/s41368-020-0074-xYoon, Yoon, Song, Yoon, Lim et al., Clinical significance of a high SARS-CoV-2 viral load in the saliva, J Korean Med Sci,
doi:10.3346/jkms.2020.35.e195Young, Fong, Chan, Mak, Ang et al., Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study, Lancet,
doi:10.1016/s0140-6736(20)31757-8{ 'indexed': {'date-parts': [[2024, 4, 4]], 'date-time': '2024-04-04T09:10:10Z', 'timestamp': 1712221810729},
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'Consistent detection of 2019 novel coronavirus in saliva. Clin Infect '
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'unstructured': 'Ott IM, Strine MS, Watkins AE, Boot M, Kalinich CC, Harden CA, et al. '
'Simply saliva: stability of SARS-CoV-2 detection negates the need for '
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'Sci. 2020. https://doi.org/10.1101/2020.08.03.20165233.',
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'unstructured': 'Meng L, Hua F, Bian Z. Coronavirus Disease 2019 (COVID-19): emerging and '
'future challenges for dental and oral medicine. J Dent Res. '
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'unstructured': 'Izzetti R, Nisi M, Gabriele M, Graziani F. COVID-19 transmission in '
'dental practice: brief review of preventive measures in Italy. J Dent '
'Res. 2020;99:1030–8. https://doi.org/10.1177/0022034520920580.',
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{ 'key': '1563_CR8',
'unstructured': 'Lu M. These are the occupations with the highest COVID-19 risk. In: '
'World Economic Forum. 20 April 2020. '
'https://www.weforum.org/agenda/2020/04/occupations-highest-covid19-risk/.'},
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'unstructured': 'Peng X, Xu X, Li Y, Cheng L, Zhou X, Ren B. Transmission routes of '
'2019-nCoV and controls in dental practice. Int J Oral Sci. 2020;12:9. '
'https://doi.org/10.1038/s41368-020-0075-9.',
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'significance of a high SARS-CoV-2 viral load in the saliva. J Korean Med '
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'Alvargonzalez JJ, López Domínguez AM, et al. Is povidone iodine '
'mouthwash effective against SARS-CoV-2? First in vivo tests Oral Dis. '
'2020. https://doi.org/10.1111/odi.13526.',
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'year': '2020',
'unstructured': 'Rao SN, Manissero D, Steele VR, Pareja J. A systematic review of the '
'clinical utility of cycle threshold values in the context of COVID-19. '
'Infect Dis The. 2020;9:573–86. '
'https://doi.org/10.1007/s40121-020-00324-3.',
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'Cetylpyridinium chloride (CPC) exhibits potent, rapid activity against '
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'https://doi.org/10.20411/pai.v2i2.200.',
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'doi-asserted-by': 'publisher',
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'author': 'R Kawana',
'year': '1997',
'unstructured': 'Kawana R, Kitamura T, Nakagomi O, Matsumoto I, Arita M, Yoshihara N, et '
'al. Inactivation of human viruses by povidone-iodine in comparison with '
'other antiseptics. Dermatology (Basel, Switzerland). 1997;195:29–35. '
'https://doi.org/10.1159/000246027.',
'journal-title': 'Dermatology (Basel, Switzerland)'},
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'volume': '69',
'author': 'D Bernstein',
'year': '1990',
'unstructured': 'Bernstein D, Schiff G, Echler G, Prince A, Feller M, Briner W. In vitro '
'virucidal effectiveness of a 0.12%-chlorhexidine gluconate mouthrinse. J '
'Dent Res. 1990;69:874–6. https://doi.org/10.1177/00220345900690030901.',
'journal-title': 'J Dent Res'},
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'author': 'VB O’Donnell',
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'SARS-CoV-2. Nat microbiol. 2020;5:536–44. '
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'formulation against upper respiratory infections. BMC Infect Dis. '
'2017;17:74. https://doi.org/10.1186/s12879-016-2177-8.',
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'unstructured': 'Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, et al. High expression of '
'ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J '
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'journal-title': 'Int J Oral Sci'},
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