Oral mouthwashes for asymptomatic to mildly symptomatic adults with COVID-19 and salivary viral load: a randomized, placebo-controlled, open-label clinical trial
Daisuke Onozuka, Satoko Takatera, Hiroo Matsuo, Hisao Yoshida, Shigeto Hamaguchi, Shungo Yamamoto, Ryuichi Minoda Sada, Koichiro Suzuki, Keiji Konishi, Satoshi Kutsuna
BMC Oral Health, doi:10.1186/s12903-024-04246-1
Background Recent randomized clinical trials suggest that the effect of using cetylpyridinium chloride (CPC) mouthwashes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in COVID-19 patients has been inconsistent. Additionally, no clinical study has investigated the effectiveness of on-demand aqueous chlorine dioxide mouthwash against COVID-19.
Methods We performed a randomized, placebo-controlled, open-label clinical trial to assess for any effects of using mouthwash on the salivary SARS-CoV-2 viral load among asymptomatic to mildly symptomatic adult COVID-19-positive patients. Patients were randomized to receive either 20 mL of 0.05% CPC, 10 mL of 0.01% on-demand aqueous chlorine dioxide, or 20 mL of placebo mouthwash (purified water) in a 1:1:1 ratio. The primary endpoint was the cycle threshold (Ct) values employed for SARS-CoV-2 salivary viral load estimation. We used linear mixed-effects models to assess for any effect of the mouthwashes on SARS-CoV-2 salivary viral load.
Results Of a total of 96 eligible participants enrolled from November 7, 2022, to January 19, 2023, 90 were accepted for the primary analysis. The use of 0.05% CPC mouthwash was not shown to be superior to placebo in change from baseline salivary Ct value at 30 min (difference vs. placebo, 0.640; 95% confidence interval [CI], -1.425 to 2.706; P = 0.543); 2 h (difference vs. placebo, 1.158; 95% CI, -0.797 to 3.112; P = 0.246); 4 h (difference vs. placebo, 1.283; 95% CI, -0.719 to 3.285; P = 0.209); 10 h (difference vs. placebo, 0.304; 95% CI, -1.777 to 2.385; P = 0.775); or 24 h (difference vs. placebo, 0.782; 95% CI, -1.195 to 2.759; P = 0.438). The use of 0.01% on-demand aqueous chlorine dioxide mouthwash was also not shown to be superior to placebo in change from baseline salivary Ct value at 30 min (difference vs. placebo, 0.905; 95% CI, -1.079 to 2.888; P = 0.371); 2 h (difference vs. placebo, 0.709; 95% CI, -1.275 to 2.693; P = 0.483); 4 h (difference vs. placebo, 0.220; 95% CI, -1.787 to 2.226; P = 0.830); 10 h (difference vs. placebo, 0.198; 95% CI, -1.901 to 2.296; P = 0.854); or 24 h (difference vs. placebo, 0.784; 95% CI, -1.236 to 2.804; P = 0.447).
Supplementary Information The online version contains supplementary material available at https://doi. org/10.1186/s12903-024-04246-1.
Supplementary Material 1 Author contributions S.K supervised the project. D.O., S.T., and S.K. made substantial contributions to conception and design. D.O., S.T., H.M., H.Y., S.H., S.Y., R.M.S., and K.K. collected data. K.S. conducted laboratory test. D.O. analyzed the data, wrote the first draft of the manuscript, and interpreted the results. D.O., S.T., H.M., H.Y., S.H., S.Y., R.M.S., K.S., K.K., and S.K. contributed to critical revision of the manuscript. All authors were involved in data interpretation and made meaningful contributions to the final submitted manuscript.
Data availability The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
Declarations Ethics approval and consent to participate This open-label, randomized, placebo-controlled clinical trial was approved by the Ethical Committee of Osaka University (No. S22003) on 6/10/2022, and was registered with the Japan Registry of Clinical Trials (jRCT) (No. jRCTs051220107) on 18/10/2022. This trial was conducted in compliance with the provisions of the Declaration of Helsinki, Good Clinical Practice Guidelines, and local regulatory requirements. Patient registration was conducted from 7/11/2022 to 19/1/2023 in Osaka, Japan, and all of the participants provided written informed consent.
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