Efficacy of mouthwash on reducing salivary SARS-CoV-2 viral load and clinical symptoms: a systematic review and meta-analysis
Authors: Zhang Mingrui , Meng Nan , Duo Hong , Yang Yuanbo , Dong Qing , Gu Jianqi 
Published: October 2023

Abstract
Background
COVID-19 has been a public health emergency of international concern (PHEIC) for a lengthy period of time. The novel coronavirus is primarily spread via aerosols at a short distance, with infected individuals releasing large amounts of aerosols when speaking and coughing. However, there is an open question regarding whether mouthwash could effectively reduce virus transmission during the COVID-19 pandemic and support the prevention of infection among medical workers.

Methods
Cochrane Library, PubMed, Web of Science, and Embase databases were systematically searched from the inception of each database to January 12, 2023 for currently available randomized clinical trials (RCTs) on the effect of mouthwash on novel coronavirus load in the oral cavity in COVID-19 patients. The treatment group received mouthwash for rinsing the mouth, while the control group received a placebo or distilled water for COVID-19 patients. The primary outcomes were CT value and viral load. Odds ratios (ORs) were estimated using a random-effects model. Subgroup and sensitivity analyses were performed to minimize the bias and the impact of heterogeneity.

Results
Thirteen RCTs were included. Seven studies reported the intervention effect of mouthwash on the CT value of novel coronavirus. The analysis results showed that the mouthwash group had a positive impact on the CT value of novel coronavirus [ SMD = 0.35, 95% CI (0.21, 0.50)] compared with the control group. In addition, subgroup analysis showed a significant positive effect of mouthwash on CT values in the treatment group compared with the control group, with chlorhexidine (CHX) [SMD = 0.33, 95% CI (0.10, 0.56)], povidone-iodine (PVP-I) [SMD = 0.61, 95% CI (0.23, 0.99)], or hydrogen peroxide (HP) [SMD = 1.04, 95% CI (0.30, 1.78)] as an ingredient of the mouthwash. Six studies reported the intervention effect of mouthwash on the viral load, 263 cases in the treatment group and 164 cases in the control group. The analysis results showed that there was no statistical difference between the mouthwash group and the control group in the viral load of novel coronavirus [SMD = -0.06, 95% CI (-0.18, 0.05)]. In the subgroup analysis by measurement time, there were statistically significant differences between the mouthwash and control groups for CT values [SMD = 0.52, 95% CI (0.31, 0.72)] and viral load [SMD =  − 0.32, 95% CI (− 0.56, − 0.07)] within 30 min of gargling.

Conclusions
In summary, mouthwash has some efficacy in reducing the viral load of novel coronavirus, especially within 30 min after rinsing the mouth. Mouthwash containing CHX, PVP-I and HP all had significant positive effects on CT values, and PVP-I-containing mouthwash may be a promising option to control novel coronavirus infections and relieve virus-related symptoms. However, studies on the dose and frequency of use of mouthwash for infection control are still lacking, which may limit the clinical application of mouthwash.

Trial registration
Protocol registration: The protocol was registered at PROSPERO (CRD42023401961).