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):1494-1501. doi: 10.1016/j.cmi.2021.05.028. Epub 2021 May 24.


Objectives: To determine if commercially available mouthwash with β-cyclodextrin and citrox (bioflavonoids) (CDCM) could decrease the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) salivary viral load.

Methods: In this randomized controlled trial, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive patients aged 18-85 years with asymptomatic to mild coronavirus disease 2019 (COVID-19) symptoms for <8 days were recruited. A total of 176 eligible patients were randomly assigned (1:1) to CDCM or placebo. Three rinses daily were performed for 7 days. Saliva sampling was performed on day 1 at 09.00 (T1), 13.00 (T2) and 18.00 (T3). On the following 6 days, one sample was taken at 15.00. Quantitative RT-PCR was used to detect SARS-CoV-2.

Results: The intention-to-treat analysis demonstrated that, over the course of 1 day, CDCM was significantly more effective than placebo 4 hours after the first dose (p 0.036), with a median percentage (log10 copies/mL) decrease T1-T2 of -12.58% (IQR -29.55% to -0.16%). The second dose maintained the low median value for the CDCM (3.08 log10 copies/mL; IQR 0-4.19), compared with placebo (3.31 log10 copies/mL; IQR 1.18-4.75). At day 7, there was still a greater median percentage (log10 copies/mL) decrease in salivary viral load over time in the CDCM group (-58.62%; IQR -100% to -34.36%) compared with the placebo group (-50.62%; IQR -100% to -27.66%). These results were confirmed by the per-protocol analysis.

Conclusions: This trial supports the relevance of using CDCM on day 1 (4 hours after the initial dose) to reduce the SARS-CoV-2 viral load in saliva. For long-term effect (7 days), CDMC appears to provide a modest benefit compared with placebo in reducing viral load in saliva.

Keywords: Citrox; Coronavirus disease 2019; Mouthwash; Saliva; Severe acute respiratory syndrome coronavirus 2; Viral load; β-cyclodextrin.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / chemistry
  • Antiviral Agents / therapeutic use*
  • Asymptomatic Infections
  • COVID-19 / prevention & control*
  • COVID-19 / transmission
  • Double-Blind Method
  • Female
  • Flavonoids / analysis
  • Flavonoids / therapeutic use
  • Humans
  • Intention to Treat Analysis
  • Male
  • Middle Aged
  • Mouthwashes / chemistry
  • Mouthwashes / therapeutic use*
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / isolation & purification
  • Saliva / virology
  • Viral Load / drug effects
  • Young Adult
  • beta-Cyclodextrins / analysis
  • beta-Cyclodextrins / therapeutic use


  • Antiviral Agents
  • Flavonoids
  • Mouthwashes
  • beta-Cyclodextrins