背景:最近的随机临床试验表明,使用氯化十六烷基吡啶(CPC)漱口水对COVID-19患者的严重急性呼吸道综合征冠状病毒2(SARS-CoV-2)病毒载量的影响不一致。此外,尚无临床研究调查按需水性二氧化氯漱口水对COVID-19的有效性。
方法:我们进行了随机,安慰剂对照,开放标签临床试验,以评估在无症状至轻度症状的成年COVID-19阳性患者中使用漱口水对唾液SARS-CoV-2病毒载量的任何影响。患者随机接受20mL的0.05%CPC,10毫升0.01%的按需二氧化氯水溶液,或20毫升安慰剂漱口水(纯净水),比例为1:1:1。主要终点是用于SARS-CoV-2唾液病毒载量估计的周期阈值(Ct)值。我们使用线性混合效应模型来评估漱口水对SARS-CoV-2唾液病毒载量的任何影响。
结果:从2022年11月7日至2023年1月19日,共有96名符合条件的参与者被纳入主要分析。在30分钟时,使用0.05%CPC漱口水与基线唾液Ct值的变化未显示出优于安慰剂(差异与安慰剂,0.640;95%置信区间[CI],-1.425至2.706;P=0.543);2h(差异与安慰剂,1.158;95%CI,-0.797至3.112;P=0.246);4h(差异与安慰剂,1.283;95%CI,-0.719至3.285;P=0.209);10h(差异与安慰剂,0.304;95%CI,-1.777至2.385;P=0.775);或24h(差异与安慰剂,0.782;95%CI,-1.195至2.759;P=0.438)。在30分钟时基线唾液Ct值的变化方面,按需使用0.01%的二氧化氯漱口水也未显示优于安慰剂(差异与安慰剂,0.905;95%CI,-1.079至2.888;P=0.371);2h(差异与安慰剂,0.709;95%CI,-1.275至2.693;P=0.483);4h(差异与安慰剂,0.220;95%CI,-1.787至2.226;P=0.830);10h(差异与安慰剂,0.198;95%CI,-1.901至2.296;P=0.854);或24h(差异与安慰剂,0.784;95%CI,-1.236至2.804;P=0.447)。
结论:与安慰剂相比,在无症状至轻度症状的COVID-19成人中,使用0.05%CPC和0.01%按需水性二氧化氯漱口水并未导致SARS-CoV-2唾液病毒载量显著降低.未来的CPC和按需水性二氧化氯漱口水对SARS-CoV-2的病毒生存力的功效研究应使用不同的样本类型并在多个人群和环境中进行。
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).
CONCLUSIONS: 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.