Could mouth rinses be an adjuvant in the treatment of SARS-CoV-2 patients? An appraisal with a systematic review.

OBJECTIVE: A wide variety of mouth rinses are available to combat micro-organisms in the oral cavity. At the present global pandemic, the need of the hour is to control the viral infection due to the novel corona virus SARS-COV-2, as its port of entry is through the receptors located in the oral and pharyngeal mucosa. This systematic literature review focuses on the in vivo studies [randomized control trials (RCTs)] done on the efficacy of existing mouth rinses which have been used in reducing the viral loads. METHODS: The electronic database which includes PubMed-MEDLINE, Google scholar, Scopus, Web of Science, EMBASE, ProQuest and CINAHL was searched from December 2019 to June 2021 with appropriate Medical Subject Headings (MeSH) terms and Boolean operators. Two reviewers independently reviewed the abstracts. RESULTS: Of the 2438 retrieved titles, 905 remained after removing duplicates. Twelve articles were eligible to be included in this review of which seven were randomized with adequate sample size. CONCLUSIONS: Mouth washes containing povidone iodine and chlorhexidine decrease the viral load transiently. Large amount of in vivo studies are of paramount importance, especially RCTs, to prove the efficacy of these mouth rinses.

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.

OBJECTIVES: To determine if commercially available mouthwash with ß-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.

Salivary and Nasal Detection of the SARS-CoV-2 Virus After Antiviral Mouthrinses (BBCovid): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: - To describe the evolution of the SARS-CoV-2 salivary viral load of patients infected with Covid-19, performing 7 days of tri-daily mouthwashes with and without antivirals. - To compare the evolution of the SARS-CoV-2 nasal and salivary viral load according to the presence or absence of antivirals in the mouthwash. TRIAL DESIGN: This is a multi-center, randomised controlled trial (RCT) with two parallel arms (1:1 ratio). PARTICIPANTS: Inclusion criteria - Age: 18-85 years old - Clinical diagnosis of Covid-19 infection - Clinical signs have been present for less than 8 days - Virological confirmation - Understanding and acceptance of the trial - Written agreement to participate in the trial Exclusion criteria - Pregnancy, breastfeeding, inability to comply with protocol, lack of written agreement - Patients using mouthwash on a regular basis (more than once a week) - Patient at risk of infectious endocarditis - Patients unable to answer questions - Uncooperative patient The clinical trial is being conducted with the collaboration of three French hospital centers: Hospital Center Emile Roux (Le Puy en Velay, France), Clinic of the Protestant Infirmary (Lyon, France) and Intercommunal Hospital Center (Mont de Marsan, France). INTERVENTION AND COMPARATOR: Eligible participants will be allocated to one of the two study groups. Intervention group: patients perform a tri-daily mouthwash with mouthwash containing antivirals (ß-cyclodextrin and Citrox®) for a period of 7 days. CONTROL GROUP: patients perform a tri-daily mouthwash with a placebo mouthwash for a period of 7 days. MAIN OUTCOMES: Primary Outcome Measures: Change from Baseline amount of SARS-CoV-2 in salivary samples at 4 and 9 hours, 1, 2, 3, 4, 5 and 6 days. Real-time PCR assays are performed to assess salivary SARS-CoV 2 viral load. SECONDARY OUTCOME MEASURES: Change from Baseline amount of SARS-CoV-2 virus in nasal samples at 6 days. Real-time PCR assays are performed to assess nasal SARS-CoV-2 viral load. RANDOMISATION: Participants meeting all eligibility requirements are allocated to one of the two study arms (mouthwash with ß-cyclodextrin and Citrox® or mouthwash without ß-cyclodextrin and Citrox®) in a 1:1 ratio using simple randomisation with computer generated random numbers. BLINDING (MASKING): Participants, doctors and nurses caring for participants, laboratory technicians and investigators assessing the outcomes will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Both the intervention and control groups will be composed of 103 participants, so the study will include a total of 206 participants. TRIAL STATUS: The current protocol version is 6, August 4th, 2020. Recruitment began on April 6, 2020 and is anticipated to be complete by April 5, 2021. As of October 2, 2020, forty-two participants have been included. TRIAL REGISTRATION: This trial was registered on 20 April 2020 at www.clinicaltrials.gov with the number NCT04352959 . FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol." The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2)."

COVID-19: A Recommendation to Examine the Effect of Mouthrinses with ß-Cyclodextrin Combined with Citrox in Preventing Infection and Progression.

Considered to be a major portal of entry for infectious agents, the oral cavity is directly associated with the evolutionary process of SARS-CoV-2 in its inhalation of ambient particles in the air and in expectorations. Some new generations of mouth rinses currently on the market have ingredients that could contribute to lower the SARS-CoV-2 viral load, and thus facilitate the fight against oral transmission. If chlorhexidine, a usual component of mouth rinse, is not efficient to kill SARS-CoV-2, the use of a mouth rinses and/or with local nasal applications that contain ß-cyclodextrins combined with flavonoids agents, such as Citrox, could provide valuable adjunctive treatment to reduce the viral load of saliva and nasopharyngeal microbiota, including potential SARS-CoV-2 carriage. We urge national agencies and authorities to start clinical trials to evaluate the preventive effects of ßCD-Citrox therapeutic oral biofilm rinses in reducing the viral load of the infection and possibly disease progression.