Efficacy of three antimicrobial mouthwashes in reducing SARS-CoV-2 viral load in the saliva of hospitalized patients: a randomized controlled pilot study

Jeniffer Perussolo, Muy-Teck Teh, Nikolaos Gkranias, Simon Tiberi, Aviva Petrie, Maria-Teresa Cutino-Moguel, Nikolaos Donos, Jeniffer Perussolo, Muy-Teck Teh, Nikolaos Gkranias, Simon Tiberi, Aviva Petrie, Maria-Teresa Cutino-Moguel, Nikolaos Donos

Abstract

This study aimed to evaluate the efficacy of 3 mouthwashes in reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in the saliva of coronavirus disease 2019 (COVID-19) patients at 30 min, 1, 2 and 3 h after rinsing. This pilot study included 40 admitted COVID-19 positive patients (10 in each group). Saliva samples were collected before rinsing and at 30 min, 1, 2 and 3 h after rinsing with: Group 1-0.2% Chlorhexidine digluconate (CHX); Group 2-1.5% Hydrogen peroxide (H2O2); Group 3-Cetylpyridinium chloride (CPC) or Group 4 (control group)-No rinsing. Viral load analysis of saliva samples was assessed by Reverse Transcription quantitative PCR. Mean log10 viral load at different time points was compared to that at baseline in all groups using a random effects linear regression analysis while for comparison between groups linear regression analysis was used. The results showed that all groups had a significantly reduced mean log10 viral load both at 2 (p = 0.036) and 3 (p = 0.041) hours compared to baseline. However, there was no difference in mean log10 viral load between any of the investigated mouthwashes and the control group (non-rinsing) at the evaluated time points. Although a reduction in the SARS-CoV-2 viral load in the saliva of COVID-19 patients was observed after rinsing with mouthwashes containing 0.2% CHX, 1.5% H2O2, or CPC, the reduction detected was similar to that achieved by the control group at the investigated time points. The findings of this study may suggest that the mechanical action of rinsing/spitting results in reduction of SARS-CoV-2 salivary load.

Conflict of interest statement

N.D. had an advisory role at GlaxoSmithKline (GSK) and was awarded a GSK Consumer Healthcare (GSKCH) research grant, which provided funding for this study. ND has also lectured for Oral-B. S.T. is a GSK Global Health Consultant. J.P., N.G., A.P., M.T. and M.C.M. do not report any competing interest.

© 2023. Springer Nature Limited.

Figures

Figure 1
Figure 1
Flowchart with trial profile.
Figure 2
Figure 2
One-step RT-qPCR workflow for quantification of salivary SARS-CoV-2 viral load using MagMAX Viral/Pathogen Nucleic Acid Isolation Kit, genesig COVID-19 qPCR Assay. Figure created using CorelDRAW Graphics Suite 2017 (version 19.1.0.419) https://www.coreldraw.com/en/pages/coreldraw-2017/.
Figure 3
Figure 3
Box plot presenting mean (cross within the box), median (horizontal line within the box), interquartile range, minimum and maximum log10 viral load for each group at baseline.
Figure 4
Figure 4
Log10 viral load for individual patients in the Groups 1 to 4 at different time points. Graphs created with Stata (StataCorp. 2021. Stata Statistical Software: Release 17. College Station, TX: StataCorp LLC.) Available at https://www.stata.com/products/.
Figure 5
Figure 5
Mean log10 viral load for each group with 95% confidence interval (CI) linked at the different time points. Graph created with Stata (StataCorp. 2021. Stata Statistical Software: Release 17. College Station, TX: StataCorp LLC.). Available at https://www.stata.com/products/.

References

    1. World Health Organization. WHO Coronavirus Disease (COVID-19) Dashboard. (Accessed 2022);
    1. Kronbichler A, Kresse D, Yoon S, Lee KH, Effenberger M, Shin JI. Asymptomatic patients as a source of COVID-19 infections: A systematic review and meta-analysis. Int. J. Infect. Dis. 2020;98:180–186. doi: 10.1016/j.ijid.2020.06.052.
    1. O’Donnell VB, Thomas D, Stanton R, Maillard JY, Murphy RC, Jones SA, et al. Potential role of oral rinses targeting the viral lipid envelope in SARS-CoV-2 infection. Function. 2020;1:1–12. doi: 10.1093/function/zqaa002.
    1. Andersson MI, Arancibia-Carcamo CV, Auckland K, Baillie JK, Barnes E, Beneke T, et al. SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus. Wellcome Open Res. 2020 doi: 10.12688/wellcomeopenres.16002.2.
    1. 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. Oral Sci. 2020;12:8. doi: 10.1038/s41368-020-0074-x.
    1. To KK, Tsang OT, Yip CC, Chan K, Wu T, Chan JM, et al. Consistent detection of 2019 novel coronavirus in saliva. Clin. Infect. Dis. 2020;2020:4–6. doi: 10.1093/cid/ciaa149.
    1. Rao M, Rashid FA, Sabri FSAH, Jamil NN, Zain R, Hashim R, et al. Comparing nasopharyngeal swab and early morning saliva for the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Clin. Infect. Dis. 2021;2:352–356. doi: 10.1093/cid/ciaa1156.
    1. Pan Y, Liu H, Chu C, Li X, Liu S, Lu S. Transmission routes of SARS-CoV-2 and protective measures in dental clinics during the COVID-19 pandemic. Am. J. Dent. 2020;33(3):129–134.
    1. Kampf G, Todt D, Pfaender S, Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents. J. Hosp. Infect. 2020;104(3):246–251. doi: 10.1016/j.jhin.2020.01.022.
    1. Caruso AA, Del PA, Lazzarino AI. Hydrogen peroxide and viral infections: A literature review with research hypothesis definition in relation to the current covid-19 pandemic. Med. Hypotheses. 2020;144:109910. doi: 10.1016/j.mehy.2020.109910.
    1. Eduardo FP, Correa L, Mansur F, Benitez C, Hamerschlak N, Pinho JRR, et al. Effectiveness of toothpastes on SARS-CoV-2 viral load in saliva. Int. Dent. J. 2022;72(6):825–831. doi: 10.1016/j.identj.2022.03.006.
    1. Eduardo FP, Correa 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(June):1–7. doi: 10.1016/j.heliyon.2021.e07346.
    1. Tartaglia GM, Tadakamadla SK, Connelly ST, Sforza C, Martín C. Adverse events associated with home use of mouthrinses: A systematic review. Ther. Adv. Drug Saf. 2019;10:1–16. doi: 10.1177/2042098619854881.
    1. Eggers M, Eickmann M, Zorn J. Rapid and effective virucidal activity of povidone- iodine products against middle east respiratory syndrome coronavirus (MERS-CoV) and modified vaccinia virus ankara (MVA) Infect. Dis. Ther. 2015;4(4):491–501. doi: 10.1007/s40121-015-0091-9.
    1. 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(3):874–876. doi: 10.1177/00220345900690030901.
    1. 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;35(20):e195. doi: 10.3346/jkms.2020.35.e195.
    1. Popkin DL, 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: 10.20411/pai.v2i2.200.
    1. Green A, Roberts G, Tobery T, Vincent C, Barili, Jone C. In vitro assessment of the virucidal activity of four mouthwashes containing Cetylpyridinium Chloride, ethanol, zinc and a mix of enzyme and proteins against a human coronavirus. bioRxiv. 2020 doi: 10.1101/2020.10.28.359257.
    1. 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;24(10):3707–3713. doi: 10.1007/s00784-020-03549-1.
    1. Seneviratne CJ, Balan P, Ko KKK, Udawatte NS, Lai D, Ng DHL, 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: 10.1007/s15010-020-01563-9.
    1. Gandhi G, Thimmappa L, Upadhya N, Carnelio S. Could mouth rinses be an adjuvant in the treatment of SARS-CoV-2 patients? An appraisal with a systematic review. Int. J. Dent. Hyg. 2022;20(1):136–144. doi: 10.1111/idh.12555.
    1. Silva A, Azevedo M, Sampaio-Maia B, Sousa-Pinto B. The effect of mouthrinses on severe acute respiratory syndrome coronavirus 2 viral load: A systematic review. J. Am. Dent. Assoc. 2022;153(7):635–648.e16. doi: 10.1016/j.adaj.2021.12.007.
    1. Garcia-Sanchez A, Peña-Cardelles JF, Ruiz S, Robles F, Ordonez-Fernandez E, Salgado-Peralvo AO, et al. Efficacy of pre-procedural mouthwashes against SARS-CoV-2: A systematic review of randomized controlled trials. J. Clin. Med. 2022 doi: 10.3390/jcm11061692.
    1. Ortega KL, Rech BO, El Haje GLC, Gallo CB, Pérez-Sayáns M, Braz-Silva PH. Do hydrogen peroxide mouthwashes have a virucidal effect? A systematic review. J. Hosp. Infect. 2020;106(4):657–662. doi: 10.1016/j.jhin.2020.10.003.
    1. Hernández-Vásquez A, Barrenechea-Pulache A, Comandé D, Azañedo D. Mouthrinses and SARS-CoV-2 viral load in saliva: A living systematic review. Evid. Based Dent. 2022 doi: 10.1038/s41432-022-0253-z.
    1. Crocker-Buque T, Williams S, Brentnall AR, Gabe R, Duffy S, Prowle JR, et al. The Barts Health NHS Trust COVID-19 cohort: characteristics, outcomes and risk scoring of patients in East London. Int. J. Tuberc. Lung Dis. 2021;25(5):358–366. doi: 10.5588/ijtld.20.0926.
    1. Urbaniak, G., & Plous, S. Research Randomizer (Version 4.0) [Computer software] (2013).
    1. RECOVERY Collaborative Group Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet. 2021;397(10285):1637–1645. doi: 10.1016/S0140-6736(21)00676-0.
    1. 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;152(11):903–908. doi: 10.1016/j.adaj.2021.05.021.
    1. 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. Sci. Rep. 2021;11(1):24392. doi: 10.1038/s41598-021-03461-y.
    1. 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 doi: 10.1093/infdis/jiaa471.
    1. 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):1–10. doi: 10.1016/j.jebdp.2021.101584.
    1. Miranda RL, Guterres A, de Azeredo Lima CH, Filho PN, Gadelha MR. Misinterpretation of viral load in COVID-19 clinical outcomes. Virus Res. 2021;296:198340. doi: 10.1016/j.virusres.2021.198340.
    1. Guest JL, Sullivan PS, Valentine-Graves M, Valencia R, Adam E, Luisi N, Nakano M, et al. Suitability and Sufficiency of telehealth clinician-observed participant- collected samples for SARS-CoV2 testing: the iCollect Cohort Pilot Study. J. Med. Internet Res. 2020;6(2):e19731. doi: 10.2196/19731.
    1. Public Health England. Understanding cycle threshold (Ct) in SARS-CoV-2 RT-PCR A guide for health protection teams. (2022)
    1. 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: 10.1038/s41586-020-2196-x.
    1. Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN, et al. SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell. 2020;181(5):1016–1035.e19. doi: 10.1016/j.cell.2020.04.035.
    1. Blanco-Melo D, Nilsson-Payant BE, Liu WC, Uhl S, Hoagland D, Møller R, et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020;181(5):1036–1045.e9. doi: 10.1016/j.cell.2020.04.026.
    1. Challenger JD, Foo CY, Wu Y, Yan AWC, Marjaneh MM, Liew F, et al. Modelling upper respiratory viral load dynamics of SARS-CoV-2. BMC Med. 2022;20(1):25. doi: 10.1186/s12916-021-02220-0.
    1. Biber A, Lev D, Mandelboim M, Lustig Y, Harmelin G, Shaham A, et al. The role of mouthwash sampling in SARS-CoV-2 diagnosis. Eur. J. Clin. Microbiol. Infect. Dis. 2021;40(10):2199–2206. doi: 10.1007/s10096-021-04320-4.

Source: PubMed

3
購読する