Efficacy of a Mouthwash Containing CHX and CPC in SARS-CoV-2–Positive Patients: A Randomized Controlled Clinical Trial

Abstract

Soon after the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, preprocedural mouthwashes were recommended for temporarily reducing intraoral viral load and infectivity of individuals potentially infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in order to protect medical personnel. Particularly, the antiseptic cetylpyridinium chloride (CPC) has shown virucidal effects against SARS-CoV-2 in vitro. Therefore, the aim of this randomized controlled clinical trial was to investigate the efficacy of a commercially available mouthwash containing CPC and chlorhexidine digluconate (CHX) at 0.05% each in SARS-CoV-2–positive patients as compared to a placebo mouthwash. Sixty-one patients who tested positive for SARS-CoV-2 with onset of symptoms within the last 72 h were included in this study. Oropharyngeal specimens were taken at baseline, whereupon patients had to gargle mouth and throat with 20 mL test or placebo (0.9% NaCl) mouthwash for 60 s. After 30 min, further oropharyngeal specimens were collected. Viral load was analyzed by quantitative reverse transcriptase polymerase chain reaction, and infectivity of oropharyngeal specimens was analyzed by virus rescue in cell culture and quantified via determination of tissue culture infectious doses 50% (TCID50). Data were analyzed nonparametrically (α = 0.05). Viral load slightly but significantly decreased upon gargling in the test group ( P = 0.0435) but not in the placebo group. Viral infectivity as measured by TCID50 also significantly decreased in the test group ( P = 0.0313), whereas there was no significant effect but a trend in the placebo group. Furthermore, it was found that the specimens from patients with a vaccine booster exhibited significantly lower infectivity at baseline as compared to those without vaccine booster ( P = 0.0231). This study indicates that a preprocedural mouthwash containing CPC and CHX could slightly but significantly reduce the viral load and infectivity in SARS-CoV-2–positive patients. Further studies are needed to corroborate these results and investigate whether the observed reductions in viral load and infectivity could translate into clinically useful effects in reducing COVID-19 transmission (German Clinical Trials Register DRKS00027812).

Effectiveness of Preprocedural Mouthwashes: A Triple-Blind Randomised Controlled Clinical Trial

“…In our clinical trial the outcome measure was detectable presence of SARS-CoV-2 as assessed NxTAG ® Respiratory Pathogen Panel as determined by multiplexed polymerase chain reaction [40]. In contrast, others have focused on SARS-CoV-2 viral load using qRT-PCR and based on cyclic threshold levels (Ct) [41] or cytopathic effects of SARS-CoV-2 as determined by 50% tissue culture infectious dose assay (TCID50) as a marker of infectivitiy [42]. However, a high level of agreement in dectection of SARS-CoV-2 from NxTAG ® Respiratory Pathogen Panel and routine COVID-19 qRT-PCR protocol assesment methods was reported: Kappa 0.98 [40].…”

Preprocedural mouthwashes for infection control in dentistry—an update

“…of patients (No. of patients with successful assessment of viral infectivity) Sampling time points Results Viral load (RT-qPCR) Assessment of viral infectivity Results Viral infectivity Barrueco et al [ 85 ] - 2% PVP-I - 1% H 2 O 2 - 0.07% CPC - 0.12% CHX - Placebo 54 (29) - Baseline - 30 min - 60 min - No significant reduction in viral load for PVP-I, H 2 O 2 , CPC, or CHX at 30 or 60 min - Significant decrease of viral load for placebo 60 min after rinsing Virus rescue in cell culture Significant decrease of 1.5 log genome copies/mL in CPC group 60 min after gargling Alemany et al [ 83 ] - 0.07% CPC - Placebo 105 (80) - Baseline - 60 min - 180 min No significant reduction in viral load in both groups Quantification of SARS-CoV-2 nucleocapsid protein by modified ELISA Significantly increased level of SARS-CoV-2 nucleocapsid protein 60 and 180 min after gargling in test group Tarragó-Gil et al [ 89 ] - 0.07% CPC - Placebo 80 (79) - Baseline - 20 min No significant reduction in viral load in both groups Quantification of SARS-CoV-2 nucleocapsid protein by modified ELISA Significantly increased level of SARS-CoV-2 nucleocapsid protein 120 min after gargling in test group Meister et al [ 75 ] - 0.1% BAC - Placebo 24 (6) - Baseline - 15 min - 30 min No significant reduction of viral load for both groups at all time points Virus rescue in cell culture Mild non-significant decrease of viral infectivity in test group Bonn et al [ 90 ] …”

“…Bonn et al conducted a placebo-controlled RCT investigating a commercially available mouthwash containing the combination of 0.05% CPC and 0.05% CHX in SARS-CoV-2 positive patients [ 90 ]. Oropharyngeal specimens were obtained at baseline and 30 min after gargling and the viral infectivity was analyzed via by rescue in cell culture and determination of TCID 50 .…”

“…Oropharyngeal specimens were obtained at baseline and 30 min after gargling and the viral infectivity was analyzed via by rescue in cell culture and determination of TCID 50 . When comparing viral infectivity at baseline and 30 min after the test mouthwash, there was a significant decrease of TCID 50 by 1.4 log 10 PFU/mL after gargling with the test mouthwash containing CPC and CHX as opposed to no significant differences in the placebo group [ 90 ].…”

“…Based on the data from the above-mentioned RCTs, there is growing evidence that use of preprocedural mouthwashes containing CPC can decrease infectivity in the saliva of SARS-CoV-2 positive individuals [ 83 , 85 , 89 , 90 ]. Nevertheless, it is not clear yet to what extent this temporary decrease in viral infectivity found in clinical trials is associated with relevant reductions in the risk of transmission of SARS-CoV-2 [ 25 ].…”