Oral mouthwashes for asymptomatic to mildly symptomatic adults with COVID-19 and salivary viral load: a randomized, placebo-controlled, open-label clinical trial

DOI record: { "DOI": "10.1186/s12903-024-04246-1", "ISSN": [ "1472-6831" ], "URL": "http://dx.doi.org/10.1186/s12903-024-04246-1", "abstract": "<jats:title>Abstract</jats:title><jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>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; <jats:italic>P</jats:italic> = 0.543); 2 h (difference vs. placebo, 1.158; 95% CI, -0.797 to 3.112; <jats:italic>P</jats:italic> = 0.246); 4 h (difference vs. placebo, 1.283; 95% CI, -0.719 to 3.285; <jats:italic>P</jats:italic> = 0.209); 10 h (difference vs. placebo, 0.304; 95% CI, -1.777 to 2.385; <jats:italic>P</jats:italic> = 0.775); or 24 h (difference vs. placebo, 0.782; 95% CI, -1.195 to 2.759; <jats:italic>P</jats:italic> = 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; <jats:italic>P</jats:italic> = 0.371); 2 h (difference vs. placebo, 0.709; 95% CI, -1.275 to 2.693; <jats:italic>P</jats:italic> = 0.483); 4 h (difference vs. placebo, 0.220; 95% CI, -1.787 to 2.226; <jats:italic>P</jats:italic> = 0.830); 10 h (difference vs. placebo, 0.198; 95% CI, -1.901 to 2.296; <jats:italic>P</jats:italic> = 0.854); or 24 h (difference vs. placebo, 0.784; 95% CI, -1.236 to 2.804; <jats:italic>P</jats:italic> = 0.447).</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>In asymptomatic to mildly symptomatic adults with COVID-19, compared to placebo, the use of 0.05% CPC and 0.01% on-demand aqueous chlorine dioxide mouthwash did not lead to a significant reduction in SARS-CoV-2 salivary viral load. Future studies of the efficacy of CPC and on-demand aqueous chlorine dioxide mouthwash on the viral viability of SARS-CoV-2 should be conducted using different specimen types and in multiple populations and settings.</jats:p>\n </jats:sec>", "alternative-id": [ "4246" ], "article-number": "491", "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "28 December 2023" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "10 April 2024" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "25 April 2024" }, { "group": { "label": "Declarations", "name": "EthicsHeading" }, "name": "Ethics", "order": 1 }, { "group": { "label": "Ethics approval and consent to participate", "name": "EthicsHeading" }, "name": "Ethics", "order": 2, "value": "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." }, { "group": { "label": "Consent for publication", "name": "EthicsHeading" }, "name": "Ethics", "order": 3, "value": "Not applicable." }, { "group": { "label": "Competing interests", "name": "EthicsHeading" }, "name": "Ethics", "order": 4, "value": "S.K., D.O., S.T., and K.K. have received research support from Earth Corporation, Tokyo, Japan. H.M., H.Y., S.H., S.Y., R.M.S., and K.S. declare no competing interests." } ], "author": [ { "affiliation": [], "family": "Onozuka", "given": "Daisuke", "sequence": "first" }, { "affiliation": [], "family": "Takatera", "given": "Satoko", "sequence": "additional" }, { "affiliation": [], "family": "Matsuo", "given": "Hiroo", "sequence": "additional" }, { "affiliation": [], "family": "Yoshida", "given": "Hisao", "sequence": "additional" }, { "affiliation": [], "family": "Hamaguchi", "given": "Shigeto", "sequence": "additional" }, { "affiliation": [], "family": "Yamamoto", "given": "Shungo", "sequence": "additional" }, { "affiliation": [], "family": "Sada", "given": "Ryuichi Minoda", "sequence": "additional" }, { "affiliation": [], "family": "Suzuki", "given": "Koichiro", "sequence": "additional" }, { "affiliation": [], "family": "Konishi", "given": "Keiji", "sequence": "additional" }, { "affiliation": [], "family": "Kutsuna", "given": "Satoshi", "sequence": "additional" } ], "container-title": "BMC Oral Health", "container-title-short": "BMC Oral Health", "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2024, 4, 25 ] ], "date-time": "2024-04-25T04:01:44Z", "timestamp": 1714017704000 }, "deposited": { "date-parts": [ [ 2024, 4, 25 ] ], "date-time": "2024-04-25T05:02:13Z", "timestamp": 1714021333000 }, "funder": [ { "name": "Earth Corporation, Tokyo, Japan" } ], "indexed": { "date-parts": [ [ 2024, 4, 26 ] ], "date-time": "2024-04-26T00:27:07Z", "timestamp": 1714091227258 }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2024, 4, 25 ] ] }, "journal-issue": { "issue": "1", "published-online": { "date-parts": [ [ 2024, 12 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 4, 25 ] ], "date-time": "2024-04-25T00:00:00Z", "timestamp": 1714003200000 } }, { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 4, 25 ] ], "date-time": "2024-04-25T00:00:00Z", "timestamp": 1714003200000 } } ], "link": [ { "URL": "https://link.springer.com/content/pdf/10.1186/s12903-024-04246-1.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/article/10.1186/s12903-024-04246-1/fulltext.html", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/content/pdf/10.1186/s12903-024-04246-1.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "prefix": "10.1186", "published": { "date-parts": [ [ 2024, 4, 25 ] ] }, "published-online": { "date-parts": [ [ 2024, 4, 25 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.1056/NEJMoa2002032", "author": "WJ Guan", "doi-asserted-by": "publisher", "first-page": "1708", "issue": "18", "journal-title": "N Engl J Med", "key": "4246_CR1", "unstructured": "Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. 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