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Efficacy of mouthrinses in reducing oral SARS-COV-2 load: a review

Abstract

Accumulated evidence has shown that the oral cavity may be an important reservoir for SARS-CoV-2. Some authors have suggested that the use of mouthrinses could reduce SARS-CoV-2 viral load in the saliva. Thus, the aim of this review was to synthesize evidence about the efficacy of mouthrinses in reducing the salivary viral load of SARS-CoV-2. 2. Nine randomized controlled trials (RCTs) have investigated the efficacy of different mouthrinses in reducing salivary SARS-CoV-2 loads. Various active ingredients have been tested in these trials: 0.5%,1% and 2% povidone-iodine, 0.2% and 0.12% chlorhexidine (CHX), 0.075% cetylpyridinium chloride (CPC), 0.075% CPC with Zinc lactate, 1% and 1.5% hydrogen peroxide (HP), 1.5% HP + 0.12% CHX and ß-cyclodextrin and citrox. The studies reported an intra-group reduction in the salivary levels of the virus, when compared with the baseline. However, the majority of these trials failed to demonstrate a significant inter-group difference between active groups and the control group relative to the decrease in salivary SARS-CoV-2 loads. Although promising, these results should be confirmed by larger trials.

SARS-CoV-2; COVID-19; Mouthwashes; Saliva

Introduction

As of August 16, 2022, the pandemic caused by SARS-Cov-2 has resulted in 588.757.628 cases of COVID-19 and 6.433.794 deaths worldwide.11. World Health Organization Coronavirus Dashboard. Geneva: World Health Organization. [cited 2022 Aug 16]. Available from: http://covid19.who.int/
http://covid19.who.int/...
The main route of transmission of SARS-CoV-2 is from person to person through small respiratory droplets, when a contaminated person coughs, sneezes, or talks.22. Grudlewska-Buda K, Wiktorczyk-Kapischke N, Wałecka-Zacharska E, Kwiecińska-Piróg J, Buszko K, Leis K, et al. SARS-CoV-2-Morphology, transmission and diagnosis during pandemic, review with element of meta-analysis. J Clin Med. 2021 May;10(9):1962. https://doi.org/10.3390/jcm10091962
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Airborne transmission through aerosols33. Robles-Romero JM, Conde-Guillén G, Safont-Montes JC, García-Padilla FM, Romero-Martín M. Behaviour of aerosols and their role in the transmission of SARS-CoV-2; a scoping review. Rev Med Virol. 2022 May;32(3):e2297. https://doi.org/10.1002/rmv.2297
https://doi.org/10.1002/rmv.2297...
can also contribute to the spread of the virus.

The oral cavity may be an important reservoir for SARS-CoV-2. The virus has been detected in the saliva44. Atieh MA, Guirguis M, Alsabeeha NH, Cannon RD. The diagnostic accuracy of saliva testing for SARS-CoV-2: A systematic review and meta-analysis. Oral Dis. 2021;•••: https://doi.org/10.1111/odi.13934
https://doi.org/10.1111/odi.13934...
and on the back of the tongue.55. To KK, Tsang OT, Leung WS, Tam AR, Wu TC, Lung DC, et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis. 2020 May;20(5):565-74. https://doi.org/10.1016/S1473-3099(20)30196-1
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Interestingly, a postmortem study in COVID-19 fatal cases detected SARS-CoV-2 in major salivary glands66. Matuck BF, Dolhnikoff M, Duarte-Neto AN, Maia G, Gomes SC, Sendyk DI, et al. Salivary glands are a target for SARS-CoV-2: a source for saliva contamination. J Pathol. 2021 Jul;254(3):239-43. https://doi.org/10.1002/path.5679
https://doi.org/10.1002/path.5679...
and periodontal tissues.77. Fernandes Matuck B, Dolhnikoff M, Maia GV, Isaac Sendyk D, Zarpellon A, Costa Gomes S, et al. Periodontal tissues are targets for Sars-Cov-2: a post-mortem study. J Oral Microbiol. 2020 Nov;13(1):1848135. https://doi.org/10.1080/20002297.2020.1848135
https://doi.org/10.1080/20002297.2020.18...
Even asymptomatic patients present high viral loads of SARS-CoV-2 in the oropharynx, which emphasizes the importance of the oral cavity in transmission of the virus.88. Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, et al. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med. 2020 Mar;382(12):1177-9. https://doi.org/10.1056/NEJMc2001737
https://doi.org/10.1056/NEJMc2001737...

Dental professionals present high risk of SARS-CoV-2 infection because of their proximity to the patients´ oral cavity.99. Mattos FF, Pordeus IA. COVID-19: a new turning point for dental practice. Brazilian Oral Research. 2020;34:e0085. https://doi.org/10.1590/1807-3107bor-2020.vol34.0085.
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Furthermore, dental procedures in which high-speed turbines, air-water syringes and ultrasonic instruments are used, generate contaminated spray and aerosols,1010. Marui VC, Souto ML, Rovai ES, Romito GA, Chambrone L, Pannuti CM. Efficacy of preprocedural mouthrinses in the reduction of microorganisms in aerosol: A systematic review. J Am Dent Assoc. 2019 Dec;150(12):1015-1026.e1. https://doi.org/10.1016/j.adaj.2019.06.024
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,1111. Kumar PS, Subramanian K. Demystifying the mist: sources of microbial bioload in dental aerosols. J Periodontol. 2020 Sep;91(9):1113-22. https://doi.org/10.1002/JPER.20-0395
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which may allow airborne transmission of the virus in the dental setting.1212. Llandro H, Allison JR, Currie CC, Edwards DC, Bowes C, Durham J, et al. Evaluating splatter and settled aerosol during orthodontic debonding: implications for the COVID-19 pandemic. Br Dent J. 2021 Jan;1-7. https://doi.org/10.1038/s41415-020-2503-9
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,1313. Ionescu AC, Brambilla E, Manzoli L, Orsini G, Gentili V, Rizzo R. Efficacy of personal protective equipment against coronavirus transmission via dental handpieces. J Am Dent Assoc. 2021 Aug;152(8):631-40. https://doi.org/10.1016/j.adaj.2021.03.007
https://doi.org/10.1016/j.adaj.2021.03.0...

Since the onset of the pandemic, reinforcement of standard practices and additional infection control measures have been recommended as a part of routine dental healthcare.1414. Center for Disease Control and Prevention. Guidance for dental settings interim infection prevention and control guidance for dental settings during the Coronavirus Disease 2019 (COVID-19) Pandemic. [cited 2021 Dec 29]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/hcp/dental-settings.html
https://www.cdc.gov/coronavirus/2019-nco...
The use of personal protective equipment, methods for reducing airborne contamination, limitation of aerosol-generating procedures, and methods for reducing surface contamination have been advocated to prevent transmission of SARS-CoV-2 infection in the dental setting.1515. Souza AF, Arruda JA, Costa FP, Bemquerer LM, Castro WH, Campos FE, et al. Safety protocols for dental care during the COVID-19 pandemic: the experience of a Brazilian hospital service. Brazilian Oral Research. 2021;35. https://doi.org/10.1590/1807-3107bor-2021.vol35.0070.
https://doi.org/10.1590/1807-3107bor-202...
Since transmission of the virus can occur through contaminated aerosols, some authors have suggested that the use of pre-procedural mouthrinses could reduce the risk of contamination by SARS-CoV-2 in the dental office.1616. Reis INR, Amaral GCLS, Mendoza AAH, Graças YT, Mendes-Correa MC, Romito GA, et al. Can preprocedural mouthrinses reduce SARS-CoV-2 load in dental aerosols? Medical Hypotheses. 2021 Jan;146:110436. https://doi.org/10.1016/j.mehy.2020.110436
https://doi.org/10.1016/j.mehy.2020.1104...

17. Yoon JG, Yoon J, Song JY, Yoon SY, Lim CS, Seong H, et al. Clinical significance of a high SARS-CoV-2 viral load in the saliva. J Korean Med Sci. 2020 May;35(20):e195. https://doi.org/10.3346/jkms.2020.35.e195
https://doi.org/10.3346/jkms.2020.35.e19...

18. Burton MJ, Clarkson JE, Goulao B, Glenny AM, McBain AJ, Schilder AG, 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 Sep;9(9):CD013627. https://doi.org/10.1002/14651858.CD013627.pub2
https://doi.org/10.1002/14651858.CD01362...

19. Fernandez MdS. Guedes MIF, Langa GPJ, Rösing CK, Cavagni J, Muniz FWMG. Virucidal efficacy of chlorhexidine: a systematic review. Odontology. 2022 Apr;110(2):376-92. https://doi.org/10.1007/s10266-021-00660-x
https://doi.org/10.1007/s10266-021-00660...
-2020. Duarte PM, Santana VT. Disinfection measures and control of SARS-COV-2 transmission. Glob Biosecurity. 2020 Apr;1(3): https://doi.org/10.31646/gbio.64
https://doi.org/10.31646/gbio.64...
The rationale is that mouthrinses with antiseptic substances could reduce the viral load in saliva and other oral tissues, thus reducing the number of active aerosolized viral particles from the oral cavity. There is good evidence that preprocedural rinses reduce bacterial load in the dental aerosol.1010. Marui VC, Souto ML, Rovai ES, Romito GA, Chambrone L, Pannuti CM. Efficacy of preprocedural mouthrinses in the reduction of microorganisms in aerosol: A systematic review. J Am Dent Assoc. 2019 Dec;150(12):1015-1026.e1. https://doi.org/10.1016/j.adaj.2019.06.024
https://doi.org/10.1016/j.adaj.2019.06.0...
However, the evidence about the efficacy of mouthrinses in reducing the viral load in the oral cavity is still controversial. Thus, the aim of this review was to synthesize the evidence about the efficacy of mouthrinses in reducing the salivary viral load of SARS-CoV-2.

Rationale for the effect of mouthrinses against SARS-COV-2

SARS-CoV-2 is susceptible to a wide variety of antiseptics, such as ethanol (> 75%), povidone-iodine (> 0.23%), and hydrogen peroxide (> 0.5%).2020. Duarte PM, Santana VT. Disinfection measures and control of SARS-COV-2 transmission. Glob Biosecurity. 2020 Apr;1(3): https://doi.org/10.31646/gbio.64
https://doi.org/10.31646/gbio.64...
The majority of the substances inactivate the virus by damaging its outer lipid layer.2121. Choi H, Chatterjee P, Lichtfouse E, Martel JA, Hwang M, Jinadatha C, et al. Classical and alternative disinfection strategies to control the COVID-19 virus in healthcare facilities: a review. Environ Chem Lett. 2021;19(3):1945-51. https://doi.org/10.1007/s10311-021-01180-4
https://doi.org/10.1007/s10311-021-01180...

Various ingredients of mouthrinses have been tested against SARS-CoV-2 in in vitro studies. Povidone iodine (PVP-I) has been the substance most tested, and has demonstrated virucidal activity against this virus.2222. Hassandarvish P, Tiong V, Mohamed NA, Arumugam H, Ananthanarayanan A, Qasuri M, et al. In vitro virucidal activity of povidone iodine gargle and mouthwash against SARS-CoV-2: implications for dental practice. Br Dent J. 2020 Dec;•••:1-4. https://doi.org/10.1038/s41415-020-2402-0
https://doi.org/10.1038/s41415-020-2402-...

23. Bidra AS, Pelletier JS, Westover JB, Frank S, Brown SM, Tessema B. Rapid In-Vitro Inactivation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Using Povidone-Iodine Oral Antiseptic Rinse. J Prosthodont. 2020 Jul;29(6):529-33. https://doi.org/10.1111/jopr.13209 PMID:32511851
https://doi.org/10.1111/jopr.13209...
-2424. 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 Aug;29(7):599-603. https://doi.org/10.1111/jopr.13220
https://doi.org/10.1111/jopr.13220...
Other substances tested include chlorhexidine (CHX)2525. 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):86-8. https://doi.org/10.4103/jisp.jisp_824_20
https://doi.org/10.4103/jisp.jisp_824_20...
,2626. Tiong V, Hassandarvish P, Bakar SA, Mohamed NA, Wan Sulaiman WS, Baharom N, et al. The effectiveness of various gargle formulations and salt water against SARS-CoV-2. Scientific Reports. 2021;11(1):20502. https://doi.org/10.1038/s41598-021-99866-w
https://doi.org/10.1038/s41598-021-99866...
and hydrogen peroxide (HP),2424. 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 Aug;29(7):599-603. https://doi.org/10.1111/jopr.13220
https://doi.org/10.1111/jopr.13220...
,2727. Meister TL, Brüggemann Y, Todt D, Conzelmann C, Müller JA, Groß R, et al. Virucidal efficacy of different oral rinses against severe Acute Respiratory Syndrome Coronavirus 2. J Infect Dis. 2020 Sep;222(8):1289-92. https://doi.org/10.1093/infdis/jiaa471
https://doi.org/10.1093/infdis/jiaa471...
with divergent results according to the study. If these active ingredients have a virucidal effect against the virus, they may be efficient in reducing the viral load of SARS-CoV-2 in the oral cavity. However, results from in vitro studies do not necessarily reflect the clinical efficacy of mouthwashes. Thus, this hypothesis needs to be investigated in in vivo studies.

In addition to the in vitro studies described above, some case reports1717. Yoon JG, Yoon J, Song JY, Yoon SY, Lim CS, Seong H, et al. Clinical significance of a high SARS-CoV-2 viral load in the saliva. J Korean Med Sci. 2020 May;35(20):e195. https://doi.org/10.3346/jkms.2020.35.e195
https://doi.org/10.3346/jkms.2020.35.e19...
,2828. Martínez Lamas L, Diz Dios P, Pérez Rodríguez MT, Del Campo Pérez V, Cabrera Alvargonzalez JJ, López Domínguez AM, et al. Is povidone iodine mouthwash effective against SARS-CoV-2? First in vivo tests. Oral Dis. 2022 Apr;28(Suppl 1 Suppl 1):908-11. https://doi.org/10.1111/odi.13526
https://doi.org/10.1111/odi.13526...
and case series2929. Gottsauner MJ, Michaelides I, Schmidt B, Scholz KJ, 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 Oct;24(10):3707-13. https://doi.org/10.1007/s00784-020-03549-1
https://doi.org/10.1007/s00784-020-03549...
have assessed the effect of pre-procedural mouthwashes in reducing the salivary viral load of patients with COVID-19 Each study tested the reduction of salivary viral load of SARS-CoV-2 using different active ingredients, namely: CHX1717. Yoon JG, Yoon J, Song JY, Yoon SY, Lim CS, Seong H, et al. Clinical significance of a high SARS-CoV-2 viral load in the saliva. J Korean Med Sci. 2020 May;35(20):e195. https://doi.org/10.3346/jkms.2020.35.e195
https://doi.org/10.3346/jkms.2020.35.e19...
PVP-I2828. Martínez Lamas L, Diz Dios P, Pérez Rodríguez MT, Del Campo Pérez V, Cabrera Alvargonzalez JJ, López Domínguez AM, et al. Is povidone iodine mouthwash effective against SARS-CoV-2? First in vivo tests. Oral Dis. 2022 Apr;28(Suppl 1 Suppl 1):908-11. https://doi.org/10.1111/odi.13526
https://doi.org/10.1111/odi.13526...
and HP.2929. Gottsauner MJ, Michaelides I, Schmidt B, Scholz KJ, 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 Oct;24(10):3707-13. https://doi.org/10.1007/s00784-020-03549-1
https://doi.org/10.1007/s00784-020-03549...
Two studies1717. Yoon JG, Yoon J, Song JY, Yoon SY, Lim CS, Seong H, et al. Clinical significance of a high SARS-CoV-2 viral load in the saliva. J Korean Med Sci. 2020 May;35(20):e195. https://doi.org/10.3346/jkms.2020.35.e195
https://doi.org/10.3346/jkms.2020.35.e19...
,2828. Martínez Lamas L, Diz Dios P, Pérez Rodríguez MT, Del Campo Pérez V, Cabrera Alvargonzalez JJ, López Domínguez AM, et al. Is povidone iodine mouthwash effective against SARS-CoV-2? First in vivo tests. Oral Dis. 2022 Apr;28(Suppl 1 Suppl 1):908-11. https://doi.org/10.1111/odi.13526
https://doi.org/10.1111/odi.13526...
detected a reduction in the salivary viral load of hospitalized patients after rinsing with 0.12% CHX and PVP-I mouthrinses, respectively. However, their results are based on the observations of two patients each, and lack a control group. Another study2929. Gottsauner MJ, Michaelides I, Schmidt B, Scholz KJ, 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 Oct;24(10):3707-13. https://doi.org/10.1007/s00784-020-03549-1
https://doi.org/10.1007/s00784-020-03549...
investigated the effect of a 1% HP rinse in 12 patients, in whom HP rinsing failed to reduce salivary viral loads. All of these studies had limitations such as the small sample size, absence of a control group, and lack of randomization. Therefore, the effect of mourthrinses on the salivary load of SARS-CoV-2 needs to be verified in randomized trials.

Randomized controlled trials

When correctly designed, conducted, and reported, randomized clinical trials (RCTs) produce the strongest reliable evidence in evaluating health interventions. In this context, we searched the internet up to July 2022 for RCTs that investigated the efficacy of mourthrinses on the reduction of the salivary load of SARS-CoV-2. The following search strategy was used in MEDLINE (via Pubmed): (mouthwash* OR “mouth rinse” OR “oral rinse” OR rinse OR hydrogen peroxide OR povidone iodine OR cetylpyridinium OR essential oils OR chlorhexidine) AND (COVID-19 OR COVID19 OR SARS-CoV-2).

Nine parallel arm randomized trials that evaluated the efficacy of mouthrinsing in reducing salivary viral load were published in the period between December 2020 and July 2022. The characteristics of the studies are shown in Table.

Table
General characteristics of randomized controlled trials that verified the efficacy of mouthrinses in reducing the salivary viral load of SARS-CoV-2

The number of participants ranged from 163030. Seneviratne CJ, Balan P, Ko KK, Udawatte NS, Lai D, Ng DH, et al. Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore. Infection. 2021 Apr;49(2):305-11. https://doi.org/10.1007/s15010-020-01563-9
https://doi.org/10.1007/s15010-020-01563...
to 176.3131. Carrouel F, Valette M, Gadea E, Esparcieux A, Illes G, Langlois ME, et al. Use of an antiviral mouthwash as a barrier measure in the SARS-CoV-2 transmission in adults with asymptomatic to mild COVID-19: a multicentre, randomized, double-blind controlled trial. Clin Microbiol Infect. 2021 Oct;27(10):1494-501. https://doi.org/10.1016/j.cmi.2021.05.028
https://doi.org/10.1016/j.cmi.2021.05.02...
Different types of active ingredients and combinations were tested: 0.5%,1% and 2% PVP-I, 0.2% and 0.12% CHX, 0.075% CPC, 0.075% CPC + Zinc lactate, 1% and 1.5% HP, 1.5% HP + 0.12% CHX and ß-cyclodextrin and citrox (CDCM).

Sterile water, distilled water, saline solution, and placebo were used as controls. Seven of the studies were located at hospitals,3030. Seneviratne CJ, Balan P, Ko KK, Udawatte NS, Lai D, Ng DH, et al. Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore. Infection. 2021 Apr;49(2):305-11. https://doi.org/10.1007/s15010-020-01563-9
https://doi.org/10.1007/s15010-020-01563...

31. Carrouel F, Valette M, Gadea E, Esparcieux A, Illes G, Langlois ME, et al. Use of an antiviral mouthwash as a barrier measure in the SARS-CoV-2 transmission in adults with asymptomatic to mild COVID-19: a multicentre, randomized, double-blind controlled trial. Clin Microbiol Infect. 2021 Oct;27(10):1494-501. https://doi.org/10.1016/j.cmi.2021.05.028
https://doi.org/10.1016/j.cmi.2021.05.02...

32. Elzein R, Abdel-Sater F, Fakhreddine S, Hanna PA, Feghali R, Hamad H, et al. In vivo evaluation of the virucidal efficacy of chlorhexidine and povidone-iodine mouthwashes against salivary SARS-CoV-2: a randomized-controlled clinical trial. J Evid Based Dent Pract. 2021;21(3):101584. https://doi.org/10.1016/j.jebdp.2021.101584
https://doi.org/10.1016/j.jebdp.2021.101...

33. Eduardo FP, Corrêa L, Heller D, Daep CA, Benitez C, Malheiros Z, et al. Salivary SARS-CoV-2 load reduction with mouthwash use:a randomized pilot clinical trial. Heliyon. 2021;7(6):e07346-e.https://doi.org/10.1016/j.heliyon.2021.e07346
https://doi.org/10.1016/j.heliyon.2021.e...

34. Ferrer MD, Barrueco ÁS, Martinez-Beneyto Y, Mateos-Moreno MV, Ausina-Márquez V, García-Vázquez E, et al. Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2. Scientific Reports. 2021;11(1):24392-. https://doi.org/10.1038/s41598-021-03461-y
https://doi.org/10.1038/s41598-021-03461...

35. Alemany A, Perez-Zsolt D, Raïch-Regué D, Muñoz-Basagoiti J, Ouchi D, Laporte-Villar C, et al. Cetylpyridinium chloride mouthwash to reduce shedding of infectious SARS-CoV-2: a double-blind randomized clinical trial. J Dent Res. 2022 Nov;101(12):1450-6. https://doi.org/10.1177/00220345221102310
https://doi.org/10.1177/0022034522110231...
-3636. Sánchez Barrueco Á, Mateos-Moreno MV, Martínez-Beneyto Y, García-Vázquez E, Campos González A, Zapardiel Ferrero J, et al. Effect of oral antiseptics in reducing SARS-CoV-2 infectivity: evidence from a randomized double-blind clinical trial. Emerg Microbes Infect. 2022 Dec;11(1):1833-42. https://doi.org/10.1080/22221751.2022.2098059
https://doi.org/10.1080/22221751.2022.20...
one in a university3737. Chaudhary P, Melkonyan A, Meethil A, Saraswat S, Hall DL, Cottle J, et al. Estimating salivary carriage of severe acute respiratory syndrome coronavirus 2 in nonsymptomatic people and efficacy of mouthrinse in reducing viral load: A randomized controlled trial. J Am Dent Assoc. 2021 Nov;152(11):903-8. https://doi.org/10.1016/j.adaj.2021.05.021
https://doi.org/10.1016/j.adaj.2021.05.0...
and another one in a Municipal Family Health Unit.3838. Costa DD, Brites C, Vaz SN, Santana DS, Santos JN, Cury PR. Chlorhexidine mouthwash reduces the salivary viral load of SARS-CoV-2: A randomized clinical trial. Oral Dis. 2022 Nov;28 Suppl 2:2500-8. https://doi.org/10.1111/odi.14086
https://doi.org/10.1111/odi.14086...

All studies were conducted with COVID-19 positive patients. The method for COVID-19 diagnosis was positive nasopharyngeal RT-PCR in all studies The investigations included symptomatic patients,3030. Seneviratne CJ, Balan P, Ko KK, Udawatte NS, Lai D, Ng DH, et al. Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore. Infection. 2021 Apr;49(2):305-11. https://doi.org/10.1007/s15010-020-01563-9
https://doi.org/10.1007/s15010-020-01563...
,3434. Ferrer MD, Barrueco ÁS, Martinez-Beneyto Y, Mateos-Moreno MV, Ausina-Márquez V, García-Vázquez E, et al. Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2. Scientific Reports. 2021;11(1):24392-. https://doi.org/10.1038/s41598-021-03461-y
https://doi.org/10.1038/s41598-021-03461...
,3636. Sánchez Barrueco Á, Mateos-Moreno MV, Martínez-Beneyto Y, García-Vázquez E, Campos González A, Zapardiel Ferrero J, et al. Effect of oral antiseptics in reducing SARS-CoV-2 infectivity: evidence from a randomized double-blind clinical trial. Emerg Microbes Infect. 2022 Dec;11(1):1833-42. https://doi.org/10.1080/22221751.2022.2098059
https://doi.org/10.1080/22221751.2022.20...
asymptomatic to mildly symptomatic patients,3131. Carrouel F, Valette M, Gadea E, Esparcieux A, Illes G, Langlois ME, et al. Use of an antiviral mouthwash as a barrier measure in the SARS-CoV-2 transmission in adults with asymptomatic to mild COVID-19: a multicentre, randomized, double-blind controlled trial. Clin Microbiol Infect. 2021 Oct;27(10):1494-501. https://doi.org/10.1016/j.cmi.2021.05.028
https://doi.org/10.1016/j.cmi.2021.05.02...
,3535. Alemany A, Perez-Zsolt D, Raïch-Regué D, Muñoz-Basagoiti J, Ouchi D, Laporte-Villar C, et al. Cetylpyridinium chloride mouthwash to reduce shedding of infectious SARS-CoV-2: a double-blind randomized clinical trial. J Dent Res. 2022 Nov;101(12):1450-6. https://doi.org/10.1177/00220345221102310
https://doi.org/10.1177/0022034522110231...
mildly to moderately symptomatic patients,3333. Eduardo FP, Corrêa L, Heller D, Daep CA, Benitez C, Malheiros Z, et al. Salivary SARS-CoV-2 load reduction with mouthwash use:a randomized pilot clinical trial. Heliyon. 2021;7(6):e07346-e.https://doi.org/10.1016/j.heliyon.2021.e07346
https://doi.org/10.1016/j.heliyon.2021.e...
,3838. Costa DD, Brites C, Vaz SN, Santana DS, Santos JN, Cury PR. Chlorhexidine mouthwash reduces the salivary viral load of SARS-CoV-2: A randomized clinical trial. Oral Dis. 2022 Nov;28 Suppl 2:2500-8. https://doi.org/10.1111/odi.14086
https://doi.org/10.1111/odi.14086...
asymptomatic, post-symptomatic, and pre-symptomatic patients.3737. Chaudhary P, Melkonyan A, Meethil A, Saraswat S, Hall DL, Cottle J, et al. Estimating salivary carriage of severe acute respiratory syndrome coronavirus 2 in nonsymptomatic people and efficacy of mouthrinse in reducing viral load: A randomized controlled trial. J Am Dent Assoc. 2021 Nov;152(11):903-8. https://doi.org/10.1016/j.adaj.2021.05.021
https://doi.org/10.1016/j.adaj.2021.05.0...
One study failed to provide information relative to patients´ symptoms.3232. Elzein R, Abdel-Sater F, Fakhreddine S, Hanna PA, Feghali R, Hamad H, et al. In vivo evaluation of the virucidal efficacy of chlorhexidine and povidone-iodine mouthwashes against salivary SARS-CoV-2: a randomized-controlled clinical trial. J Evid Based Dent Pract. 2021;21(3):101584. https://doi.org/10.1016/j.jebdp.2021.101584
https://doi.org/10.1016/j.jebdp.2021.101...
The primary outcome of six studies was change in cycle threshold (Ct) values of salivary SARS-CoV-23030. Seneviratne CJ, Balan P, Ko KK, Udawatte NS, Lai D, Ng DH, et al. Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore. Infection. 2021 Apr;49(2):305-11. https://doi.org/10.1007/s15010-020-01563-9
https://doi.org/10.1007/s15010-020-01563...
,3232. Elzein R, Abdel-Sater F, Fakhreddine S, Hanna PA, Feghali R, Hamad H, et al. In vivo evaluation of the virucidal efficacy of chlorhexidine and povidone-iodine mouthwashes against salivary SARS-CoV-2: a randomized-controlled clinical trial. J Evid Based Dent Pract. 2021;21(3):101584. https://doi.org/10.1016/j.jebdp.2021.101584
https://doi.org/10.1016/j.jebdp.2021.101...
,3333. Eduardo FP, Corrêa L, Heller D, Daep CA, Benitez C, Malheiros Z, et al. Salivary SARS-CoV-2 load reduction with mouthwash use:a randomized pilot clinical trial. Heliyon. 2021;7(6):e07346-e.https://doi.org/10.1016/j.heliyon.2021.e07346
https://doi.org/10.1016/j.heliyon.2021.e...
,3636. Sánchez Barrueco Á, Mateos-Moreno MV, Martínez-Beneyto Y, García-Vázquez E, Campos González A, Zapardiel Ferrero J, et al. Effect of oral antiseptics in reducing SARS-CoV-2 infectivity: evidence from a randomized double-blind clinical trial. Emerg Microbes Infect. 2022 Dec;11(1):1833-42. https://doi.org/10.1080/22221751.2022.2098059
https://doi.org/10.1080/22221751.2022.20...

37. Chaudhary P, Melkonyan A, Meethil A, Saraswat S, Hall DL, Cottle J, et al. Estimating salivary carriage of severe acute respiratory syndrome coronavirus 2 in nonsymptomatic people and efficacy of mouthrinse in reducing viral load: A randomized controlled trial. J Am Dent Assoc. 2021 Nov;152(11):903-8. https://doi.org/10.1016/j.adaj.2021.05.021
https://doi.org/10.1016/j.adaj.2021.05.0...
-3838. Costa DD, Brites C, Vaz SN, Santana DS, Santos JN, Cury PR. Chlorhexidine mouthwash reduces the salivary viral load of SARS-CoV-2: A randomized clinical trial. Oral Dis. 2022 Nov;28 Suppl 2:2500-8. https://doi.org/10.1111/odi.14086
https://doi.org/10.1111/odi.14086...
and in three studies3131. Carrouel F, Valette M, Gadea E, Esparcieux A, Illes G, Langlois ME, et al. Use of an antiviral mouthwash as a barrier measure in the SARS-CoV-2 transmission in adults with asymptomatic to mild COVID-19: a multicentre, randomized, double-blind controlled trial. Clin Microbiol Infect. 2021 Oct;27(10):1494-501. https://doi.org/10.1016/j.cmi.2021.05.028
https://doi.org/10.1016/j.cmi.2021.05.02...
,3434. Ferrer MD, Barrueco ÁS, Martinez-Beneyto Y, Mateos-Moreno MV, Ausina-Márquez V, García-Vázquez E, et al. Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2. Scientific Reports. 2021;11(1):24392-. https://doi.org/10.1038/s41598-021-03461-y
https://doi.org/10.1038/s41598-021-03461...
,3535. Alemany A, Perez-Zsolt D, Raïch-Regué D, Muñoz-Basagoiti J, Ouchi D, Laporte-Villar C, et al. Cetylpyridinium chloride mouthwash to reduce shedding of infectious SARS-CoV-2: a double-blind randomized clinical trial. J Dent Res. 2022 Nov;101(12):1450-6. https://doi.org/10.1177/00220345221102310
https://doi.org/10.1177/0022034522110231...
it was the number of RNA copies per mL of saliva (log10 copies/mL) after mouthrinsing. In one study,3636. Sánchez Barrueco Á, Mateos-Moreno MV, Martínez-Beneyto Y, García-Vázquez E, Campos González A, Zapardiel Ferrero J, et al. Effect of oral antiseptics in reducing SARS-CoV-2 infectivity: evidence from a randomized double-blind clinical trial. Emerg Microbes Infect. 2022 Dec;11(1):1833-42. https://doi.org/10.1080/22221751.2022.2098059
https://doi.org/10.1080/22221751.2022.20...
in addition to the Ct values, the infectious viral load was assessed in cell cultures, and in another study,3535. Alemany A, Perez-Zsolt D, Raïch-Regué D, Muñoz-Basagoiti J, Ouchi D, Laporte-Villar C, et al. Cetylpyridinium chloride mouthwash to reduce shedding of infectious SARS-CoV-2: a double-blind randomized clinical trial. J Dent Res. 2022 Nov;101(12):1450-6. https://doi.org/10.1177/00220345221102310
https://doi.org/10.1177/0022034522110231...
apart from the RNA copies per mL of saliva, levels of SARS-CoV-2 nucleocapsid protein of lysed viruses were verified after mouthrinsing.

One investigation3030. Seneviratne CJ, Balan P, Ko KK, Udawatte NS, Lai D, Ng DH, et al. Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore. Infection. 2021 Apr;49(2):305-11. https://doi.org/10.1007/s15010-020-01563-9
https://doi.org/10.1007/s15010-020-01563...
verified that 0.075% CPC and 0.5% PI mouthrinses significantly decreased SARS-Cov-2 salivary viral load when compared with the control. No significant difference between CHX and water was verified. Elzein et al.3232. Elzein R, Abdel-Sater F, Fakhreddine S, Hanna PA, Feghali R, Hamad H, et al. In vivo evaluation of the virucidal efficacy of chlorhexidine and povidone-iodine mouthwashes against salivary SARS-CoV-2: a randomized-controlled clinical trial. J Evid Based Dent Pract. 2021;21(3):101584. https://doi.org/10.1016/j.jebdp.2021.101584
https://doi.org/10.1016/j.jebdp.2021.101...
reported that 1% PVP-I and 0.2% CHX were effective against salivary SARS-CoV-2 compared with the control group, 5 minutes after rinsing. No significant difference was verified between the test groups. Another investigation3737. Chaudhary P, Melkonyan A, Meethil A, Saraswat S, Hall DL, Cottle J, et al. Estimating salivary carriage of severe acute respiratory syndrome coronavirus 2 in nonsymptomatic people and efficacy of mouthrinse in reducing viral load: A randomized controlled trial. J Am Dent Assoc. 2021 Nov;152(11):903-8. https://doi.org/10.1016/j.adaj.2021.05.021
https://doi.org/10.1016/j.adaj.2021.05.0...
demonstrated that 0.5% PI, 0.12% CHX, and 1% HP mouthrinses significantly decreased viral load by 61– 89% at 15 minutes and by 70–97% at 45 minutes. However, there were no significant differences between any of the active groups and the control group. Another group3131. Carrouel F, Valette M, Gadea E, Esparcieux A, Illes G, Langlois ME, et al. Use of an antiviral mouthwash as a barrier measure in the SARS-CoV-2 transmission in adults with asymptomatic to mild COVID-19: a multicentre, randomized, double-blind controlled trial. Clin Microbiol Infect. 2021 Oct;27(10):1494-501. https://doi.org/10.1016/j.cmi.2021.05.028
https://doi.org/10.1016/j.cmi.2021.05.02...
reported that CDCM, three rinses daily, was significantly more effective than the placebo, 4 hours after the first dose, and the second dose maintained a significantly lower value. Furthermore, at day 7, there was still a greater median percentage decrease in salivary viral load over the time in the test group compared with the placebo. One of the trials3333. Eduardo FP, Corrêa L, Heller D, Daep CA, Benitez C, Malheiros Z, et al. Salivary SARS-CoV-2 load reduction with mouthwash use:a randomized pilot clinical trial. Heliyon. 2021;7(6):e07346-e.https://doi.org/10.1016/j.heliyon.2021.e07346
https://doi.org/10.1016/j.heliyon.2021.e...
showed that rinsing with three different mouthrinses (CPC + Zn, HP and CHX) temporarily reduced the salivary load of SARS-CoV-2 after 30 and 60 minutes post-rinsing in relation to baseline and this effect was not verified in the control. Nevertheless, there were no significant differences between the tests and the control group. Although HP effectively reduced the viral load immediately after rinsing, it returned to its baseline value within 60 minutes after rinsing. The lack of substantivity of HP might explain this finding. The sequential rinse of CHX after HP did not provide any additional benefits. Another study3838. Costa DD, Brites C, Vaz SN, Santana DS, Santos JN, Cury PR. Chlorhexidine mouthwash reduces the salivary viral load of SARS-CoV-2: A randomized clinical trial. Oral Dis. 2022 Nov;28 Suppl 2:2500-8. https://doi.org/10.1111/odi.14086
https://doi.org/10.1111/odi.14086...
also reported significant reduction in viral load in the test groups compared with the control. The effect of CHX was observed after 5 and 60 minutes. In contrast, one of the trials3434. Ferrer MD, Barrueco ÁS, Martinez-Beneyto Y, Mateos-Moreno MV, Ausina-Márquez V, García-Vázquez E, et al. Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2. Scientific Reports. 2021;11(1):24392-. https://doi.org/10.1038/s41598-021-03461-y
https://doi.org/10.1038/s41598-021-03461...
showed that none of the mouthrinses tested (PVP-I, HP, CPC and CHX) significantly reduced viral load at 30 minutes, 1- and 2-hour post-rinsing, compared with the control. Nevertheless, the results were highly divergent among participants. Clear decreases were verified in some participants or at some time points and increases at other times. Along the same line, another group3535. Alemany A, Perez-Zsolt D, Raïch-Regué D, Muñoz-Basagoiti J, Ouchi D, Laporte-Villar C, et al. Cetylpyridinium chloride mouthwash to reduce shedding of infectious SARS-CoV-2: a double-blind randomized clinical trial. J Dent Res. 2022 Nov;101(12):1450-6. https://doi.org/10.1177/00220345221102310
https://doi.org/10.1177/0022034522110231...
verified no differences between the test and control relative to viral load reduction. Furthermore, levels of SARS-CoV-2 nucleocapsid protein of lysed viruses were significantly higher in the CPC group compared with the control group at 1 and 3 hours post-rinsing. One of the investigations3636. Sánchez Barrueco Á, Mateos-Moreno MV, Martínez-Beneyto Y, García-Vázquez E, Campos González A, Zapardiel Ferrero J, et al. Effect of oral antiseptics in reducing SARS-CoV-2 infectivity: evidence from a randomized double-blind clinical trial. Emerg Microbes Infect. 2022 Dec;11(1):1833-42. https://doi.org/10.1080/22221751.2022.2098059
https://doi.org/10.1080/22221751.2022.20...
showed no significant reduction in viral load in HP and CHX groups. There was a significant reduction in numbers of salivary viral copies and viral infectivity in the CPC group, 1 hour after mouthrinsing. However, there was no significant reduction in viral load in PVP-I, HP and CHX groups, compared with the control.

Critical review of the evidence

The evidence from the nine RCTs relative to reducing viral loads in saliva was controversial. Although the majority of studies verified significant reduction in intragroup viral loads, there was contrasting evidence when the active groups were compared with a control group. Some studies showed a significant reduction in viral load when using 0.5% PVP-I,3030. Seneviratne CJ, Balan P, Ko KK, Udawatte NS, Lai D, Ng DH, et al. Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore. Infection. 2021 Apr;49(2):305-11. https://doi.org/10.1007/s15010-020-01563-9
https://doi.org/10.1007/s15010-020-01563...
1% PVP-I,3232. Elzein R, Abdel-Sater F, Fakhreddine S, Hanna PA, Feghali R, Hamad H, et al. In vivo evaluation of the virucidal efficacy of chlorhexidine and povidone-iodine mouthwashes against salivary SARS-CoV-2: a randomized-controlled clinical trial. J Evid Based Dent Pract. 2021;21(3):101584. https://doi.org/10.1016/j.jebdp.2021.101584
https://doi.org/10.1016/j.jebdp.2021.101...
0.075% CPC,3030. Seneviratne CJ, Balan P, Ko KK, Udawatte NS, Lai D, Ng DH, et al. Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore. Infection. 2021 Apr;49(2):305-11. https://doi.org/10.1007/s15010-020-01563-9
https://doi.org/10.1007/s15010-020-01563...
0.2% CHX,3232. Elzein R, Abdel-Sater F, Fakhreddine S, Hanna PA, Feghali R, Hamad H, et al. In vivo evaluation of the virucidal efficacy of chlorhexidine and povidone-iodine mouthwashes against salivary SARS-CoV-2: a randomized-controlled clinical trial. J Evid Based Dent Pract. 2021;21(3):101584. https://doi.org/10.1016/j.jebdp.2021.101584
https://doi.org/10.1016/j.jebdp.2021.101...
0.12% CHX3838. Costa DD, Brites C, Vaz SN, Santana DS, Santos JN, Cury PR. Chlorhexidine mouthwash reduces the salivary viral load of SARS-CoV-2: A randomized clinical trial. Oral Dis. 2022 Nov;28 Suppl 2:2500-8. https://doi.org/10.1111/odi.14086
https://doi.org/10.1111/odi.14086...
and CDCM,3131. Carrouel F, Valette M, Gadea E, Esparcieux A, Illes G, Langlois ME, et al. Use of an antiviral mouthwash as a barrier measure in the SARS-CoV-2 transmission in adults with asymptomatic to mild COVID-19: a multicentre, randomized, double-blind controlled trial. Clin Microbiol Infect. 2021 Oct;27(10):1494-501. https://doi.org/10.1016/j.cmi.2021.05.028
https://doi.org/10.1016/j.cmi.2021.05.02...
when compared with the control group. Others did not indicate a significant reduction when using 0.2% CHX,3030. Seneviratne CJ, Balan P, Ko KK, Udawatte NS, Lai D, Ng DH, et al. Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore. Infection. 2021 Apr;49(2):305-11. https://doi.org/10.1007/s15010-020-01563-9
https://doi.org/10.1007/s15010-020-01563...
0.12% CHX,3333. Eduardo FP, Corrêa L, Heller D, Daep CA, Benitez C, Malheiros Z, et al. Salivary SARS-CoV-2 load reduction with mouthwash use:a randomized pilot clinical trial. Heliyon. 2021;7(6):e07346-e.https://doi.org/10.1016/j.heliyon.2021.e07346
https://doi.org/10.1016/j.heliyon.2021.e...
,3434. Ferrer MD, Barrueco ÁS, Martinez-Beneyto Y, Mateos-Moreno MV, Ausina-Márquez V, García-Vázquez E, et al. Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2. Scientific Reports. 2021;11(1):24392-. https://doi.org/10.1038/s41598-021-03461-y
https://doi.org/10.1038/s41598-021-03461...
,3737. Chaudhary P, Melkonyan A, Meethil A, Saraswat S, Hall DL, Cottle J, et al. Estimating salivary carriage of severe acute respiratory syndrome coronavirus 2 in nonsymptomatic people and efficacy of mouthrinse in reducing viral load: A randomized controlled trial. J Am Dent Assoc. 2021 Nov;152(11):903-8. https://doi.org/10.1016/j.adaj.2021.05.021
https://doi.org/10.1016/j.adaj.2021.05.0...
0.075% CPC,3333. Eduardo FP, Corrêa L, Heller D, Daep CA, Benitez C, Malheiros Z, et al. Salivary SARS-CoV-2 load reduction with mouthwash use:a randomized pilot clinical trial. Heliyon. 2021;7(6):e07346-e.https://doi.org/10.1016/j.heliyon.2021.e07346
https://doi.org/10.1016/j.heliyon.2021.e...

34. Ferrer MD, Barrueco ÁS, Martinez-Beneyto Y, Mateos-Moreno MV, Ausina-Márquez V, García-Vázquez E, et al. Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2. Scientific Reports. 2021;11(1):24392-. https://doi.org/10.1038/s41598-021-03461-y
https://doi.org/10.1038/s41598-021-03461...
-3535. Alemany A, Perez-Zsolt D, Raïch-Regué D, Muñoz-Basagoiti J, Ouchi D, Laporte-Villar C, et al. Cetylpyridinium chloride mouthwash to reduce shedding of infectious SARS-CoV-2: a double-blind randomized clinical trial. J Dent Res. 2022 Nov;101(12):1450-6. https://doi.org/10.1177/00220345221102310
https://doi.org/10.1177/0022034522110231...
0.5% PVP-I,3737. Chaudhary P, Melkonyan A, Meethil A, Saraswat S, Hall DL, Cottle J, et al. Estimating salivary carriage of severe acute respiratory syndrome coronavirus 2 in nonsymptomatic people and efficacy of mouthrinse in reducing viral load: A randomized controlled trial. J Am Dent Assoc. 2021 Nov;152(11):903-8. https://doi.org/10.1016/j.adaj.2021.05.021
https://doi.org/10.1016/j.adaj.2021.05.0...
2% PVP-I,3434. Ferrer MD, Barrueco ÁS, Martinez-Beneyto Y, Mateos-Moreno MV, Ausina-Márquez V, García-Vázquez E, et al. Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2. Scientific Reports. 2021;11(1):24392-. https://doi.org/10.1038/s41598-021-03461-y
https://doi.org/10.1038/s41598-021-03461...
,3636. Sánchez Barrueco Á, Mateos-Moreno MV, Martínez-Beneyto Y, García-Vázquez E, Campos González A, Zapardiel Ferrero J, et al. Effect of oral antiseptics in reducing SARS-CoV-2 infectivity: evidence from a randomized double-blind clinical trial. Emerg Microbes Infect. 2022 Dec;11(1):1833-42. https://doi.org/10.1080/22221751.2022.2098059
https://doi.org/10.1080/22221751.2022.20...
1% HP3434. Ferrer MD, Barrueco ÁS, Martinez-Beneyto Y, Mateos-Moreno MV, Ausina-Márquez V, García-Vázquez E, et al. Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2. Scientific Reports. 2021;11(1):24392-. https://doi.org/10.1038/s41598-021-03461-y
https://doi.org/10.1038/s41598-021-03461...
,3636. Sánchez Barrueco Á, Mateos-Moreno MV, Martínez-Beneyto Y, García-Vázquez E, Campos González A, Zapardiel Ferrero J, et al. Effect of oral antiseptics in reducing SARS-CoV-2 infectivity: evidence from a randomized double-blind clinical trial. Emerg Microbes Infect. 2022 Dec;11(1):1833-42. https://doi.org/10.1080/22221751.2022.2098059
https://doi.org/10.1080/22221751.2022.20...
,3737. Chaudhary P, Melkonyan A, Meethil A, Saraswat S, Hall DL, Cottle J, et al. Estimating salivary carriage of severe acute respiratory syndrome coronavirus 2 in nonsymptomatic people and efficacy of mouthrinse in reducing viral load: A randomized controlled trial. J Am Dent Assoc. 2021 Nov;152(11):903-8. https://doi.org/10.1016/j.adaj.2021.05.021
https://doi.org/10.1016/j.adaj.2021.05.0...
compared with the control. Nevertheless, assessing the viral load might not be an adequate method for determining the efficacy of substances targeting the viral envelope but not the viral RNA. There is evidence that RNA may persist in saliva after the disruption of virus particles, probably due to protection by protein complexes.3939. Park NJ, Li Y, Yu T, Brinkman BM, Wong DT. Characterization of RNA in saliva. Clin Chem. 2006 Jun;52(6):988-94. https://doi.org/10.1373/clinchem.2005.063206
https://doi.org/10.1373/clinchem.2005.06...
RNA extraction methods can identify the RNA irrespective of its status (i.e., immerse within intact viral particles or released from disrupted particles). Therefore, real-time PCR for viral detection might not indicate the presence of complete viral particles.3535. Alemany A, Perez-Zsolt D, Raïch-Regué D, Muñoz-Basagoiti J, Ouchi D, Laporte-Villar C, et al. Cetylpyridinium chloride mouthwash to reduce shedding of infectious SARS-CoV-2: a double-blind randomized clinical trial. J Dent Res. 2022 Nov;101(12):1450-6. https://doi.org/10.1177/00220345221102310
https://doi.org/10.1177/0022034522110231...
It is not known whether any residual viral genome equivalents identified are infectious.3434. Ferrer MD, Barrueco ÁS, Martinez-Beneyto Y, Mateos-Moreno MV, Ausina-Márquez V, García-Vázquez E, et al. Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2. Scientific Reports. 2021;11(1):24392-. https://doi.org/10.1038/s41598-021-03461-y
https://doi.org/10.1038/s41598-021-03461...

On the other hand, one study exhibited a significant increase in nucleocapsid protein levels in saliva, indicating enhanced disruption of viral particles by CPC compared with the control at 1 and 3 hours after mouthrinsing. Baseline levels were similar in the groups, and the disruption of nucleocapsid protein was increasingly higher in the test group during the following assessments.3535. Alemany A, Perez-Zsolt D, Raïch-Regué D, Muñoz-Basagoiti J, Ouchi D, Laporte-Villar C, et al. Cetylpyridinium chloride mouthwash to reduce shedding of infectious SARS-CoV-2: a double-blind randomized clinical trial. J Dent Res. 2022 Nov;101(12):1450-6. https://doi.org/10.1177/00220345221102310
https://doi.org/10.1177/0022034522110231...
This finding showed evidence of the potential of CPC for reducing the spread of viruses.

Another study3636. Sánchez Barrueco Á, Mateos-Moreno MV, Martínez-Beneyto Y, García-Vázquez E, Campos González A, Zapardiel Ferrero J, et al. Effect of oral antiseptics in reducing SARS-CoV-2 infectivity: evidence from a randomized double-blind clinical trial. Emerg Microbes Infect. 2022 Dec;11(1):1833-42. https://doi.org/10.1080/22221751.2022.2098059
https://doi.org/10.1080/22221751.2022.20...
for the first time evaluated the virus infectivity in saliva samples in cell cultures (infectious viral load) and indicated a significant reduction in virus infectivity in the CPC group compared with the control, 1-hour post-rinsing. The decrease in the mean quantity of infectious viruses corresponded to a reduction of 97.16% in virus infectivity. Based on this data, a significant antiviral effect was achieved. However, it was not immediate. One hour of waiting after mouthrinsing would be required for a significant antiviral effect. As it was the only study about the effects of mouthrinses in virus infectivity, the use of mouthrinses should be further explored using this methodology.

Other aspects should be investigated in future studies, such as the influence of modification in product dosages or concentration, as well as rinsing time and the time frame of saliva sampling after mouthwash. Additional baseline data such as a complete oral exam could also be considered. Furthermore, given the difficulties in culturing SARS-CoV-2 virus from clinical specimens, using viral RNA load as a surrogate continues to be a reasonable approach. Nonetheless, it is important to clarify that viral analyses performed by RT-PCR are incapable of determining the viability and transmissibility of viruses. Finally, it is important to recall that the majority of the trials presented small samples sizes, which could be associated with type II error. In other words, these studies may be underpowered to detect differences between the groups. Thus, future studies with large sample sizes and viral culture are necessary before definitive conclusions can be drawn.

Conclusions

So far, there is no robust evidence that mouthrinses are effective for reducing the salivary loads of SARS-CoV-2. More randomized trials with larger sample sizes are necessary.

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Publication Dates

  • Publication in this collection
    28 Apr 2023
  • Date of issue
    2023

History

  • Received
    23 Feb 2022
  • Accepted
    21 Nov 2022
  • Reviewed
    11 Jan 2023
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