Bauru School of Dentistry of University of São Paulo, Al. Dr. Octavio Pinheiro Brisolla, 9-75, Vila Universitária, Bauru, São Paulo, 17012-901, Brazil.
Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil.
Sci Rep. 2021 Oct 7;11(1):19937. doi: 10.1038/s41598-021-99013-5.
The risk of contamination and dissemination by SARS-CoV-2 has a strong link with nasal, oral and pharyngeal cavities. Recently, our research group observed the promising performance of an anionic phthalocyanine derivative (APD) used in a mouthwash protocol without photoexcitation; this protocol improved the general clinical condition of patients infected with SARS-CoV-2. The present two-arm study evaluated in vitro the antiviral activity and cytotoxicity of APD. Additionally, a triple-blind randomized controlled trial was conducted with 41 hospitalized patients who tested positive for COVID-19. All the included patients received World Health Organization standard care hospital treatment (non-intensive care) plus active mouthwash (experimental group AM/n = 20) or nonactive mouthwash (control group NAM/n = 21). The adjunct mouthwash intervention protocol used in both groups consisted one-minute gargling/rinsing / 5 times/day until hospital discharge. Groups were compared considering age, number of comorbidities, duration of symptoms prior admission and length of hospital stay (LOS). The associations between group and sex, age range, presence of comorbidities, admission to Intensive care unit (ICU) and death were also evaluated. The in vitro evaluation demonstrated that APD compound was highly effective for reduction of SARS-CoV-2 viral load in the 1.0 mg/mL (99.96%) to 0.125 mg/mL (92.65%) range without causing cytotoxicity. Regarding the clinical trial, the median LOS of the AM group was significantly shortened (4 days) compared with that of the NAM group (7 days) (p = 0.0314). Additionally, gargling/rinsing with APD was very helpful in reducing the severity of symptoms (no ICU care was needed) compared to not gargling/rinsing with APD (28.6% of the patients in the NAM group needed ICU care, and 50% of this ICU subgroup passed way, p = 0.0207). This study indicated that the mechanical action of the protocol involving mouthwash containing a compound with antiviral effects against SARS-CoV-2 may reduce the symptoms of the patients and the spread of infection. The use of APD in a mouthwash as an adjuvant the hospital COVID-19 treatment presented no contraindication and reduced the hospital stay period.Trial registration: The clinical study was registered at REBEC-Brazilian Clinical Trial Register (RBR-58ftdj).
SARS-CoV-2 的污染和传播风险与鼻腔、口腔和咽腔密切相关。最近，我们的研究小组观察到一种阴离子酞菁衍生物（APD）在未经光激发的漱口方案中的表现有很大的前景，该方案改善了 SARS-CoV-2 感染患者的一般临床状况。本项双盲随机对照试验评估了 APD 的抗病毒活性和细胞毒性。此外，我们还对 41 名 COVID-19 检测呈阳性的住院患者进行了一项三盲随机对照试验。所有纳入的患者均接受了世界卫生组织（WHO）标准的医院治疗（非重症监护），加用活性漱口水（实验组 AM/n=20）或非活性漱口水（对照组 NAM/n=21）。两组均采用一分钟漱口/冲洗/每天 5 次的辅助漱口干预方案，直至出院。比较两组患者的年龄、合并症数量、入院前症状持续时间和住院时间（LOS）。还评估了组间与性别、年龄范围、合并症存在、入住重症监护病房（ICU）和死亡之间的关系。体外评估表明，APD 化合物在 1.0mg/mL（99.96%）至 0.125mg/mL（92.65%）范围内对 SARS-CoV-2 病毒载量的减少非常有效，且无细胞毒性。关于临床试验，AM 组的中位 LOS 明显缩短（4 天），与 NAM 组（7 天）相比（p=0.0314）。此外，与不使用 APD 漱口相比，使用 APD 漱口（APD）非常有助于减轻症状的严重程度（无需 ICU 护理）（NAM 组中有 28.6%的患者需要 ICU 护理，其中 50%的 ICU 亚组死亡，p=0.0207）。这项研究表明，含有抗 SARS-CoV-2 病毒作用的化合物的漱口方案的机械作用可能会减轻患者的症状和感染的传播。在 COVID-19 医院治疗中使用 APD 漱口水作为辅助手段没有禁忌症，并缩短了住院时间。试验注册：该临床研究在巴西临床试验注册中心（REBEC-RBR-58ftdj）进行了注册。
