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2019冠状病毒病大流行期间病毒呼吸道感染的长期预防:一项随机、开放、对照、探索性临床研究

For the Long-Term Prevention of Viral Respiratory Tract Infections During Covid-19 Pandemic: A Randomized, Open, Controlled, Exploratory Clinical Study.

作者信息

Kolev Emil, Mircheva Lilyana, Edwards Michael R, Johnston Sebastian L, Kalinov Krassimir, Stange Rainer, Gancitano Giuseppe, Berghe Wim Vanden, Kreft Samo

机构信息

Clinical Research Center DCC Convex Ltd., Sofia, Bulgaria.

Virtus Respiratory Research Limited, London Bioscience Innovation Centre, London, United Kingdom.

出版信息

Front Pharmacol. 2022 Apr 26;13:856410. doi: 10.3389/fphar.2022.856410. eCollection 2022.

Abstract

SARS-CoV-2 vaccination is effective in preventing severe Covid-19, but efficacy in reducing viral load and transmission wanes over time. In addition, the emergence of novel SARS-CoV-2 variants increases the threat of uncontrolled dissemination and additional antiviral therapies are urgently needed for effective containment. In previous studies demonstrated strong antiviral activity against enveloped viruses, including SARS-CoV-2. In this study, we examined the potential of in preventing and treating respiratory tract infections (RTIs) and in particular, SARS-CoV-2 infections. 120 healthy volunteers (m,f, 18-75 years) were randomly assigned to prevention or control group without any intervention. After a run-in week, participants went through 3 prevention cycles of 2, 2 and 1 month with daily 2,400 mg extract (Echinaforce, EF). The prevention cycles were interrupted by breaks of 1 week. Acute respiratory symptoms were treated with 4,000 mg EF for up to 10 days, and their severity assessed a diary. Naso/oropharyngeal swabs and venous blood samples were routinely collected every month and during acute illnesses for detection and identification of respiratory viruses, including SARS-CoV-2 RT-qPCR and serology. Summarized over all phases of prevention, 21 and 29 samples tested positive for any virus in the EF and control group, of which 5 and 14 samples tested SARS-CoV-2 positive (RR = 0.37, Chi-square test, = 0.03). Overall, 10 and 14 symptomatic episodes occurred, of which 5 and 8 were Covid-19 (RR = 0.70, Chi-square test, > 0.05). EF treatment when applied during acute episodes significantly reduced the overall virus load by at least 2.12 log or approx. 99% (-test, < 0.05), the time to virus clearance by 8.0 days for all viruses (Wilcoxon test, = 0.02) and by 4.8 days for SARS-CoV-2 ( > 0.05) in comparison to control. Finally, EF treatment significantly reduced fever days (1 day vs 11 days, Chi-square test, = 0.003) but not the overall symptom severity. There were fewer Covid-19 related hospitalizations in the EF treatment group ( = 0 vs = 2). EF exhibited antiviral effects and reduced the risk of viral RTIs, including SARS-CoV-2. By substantially reducing virus loads in infected subjects, EF offers a supportive addition to existing mandated treatments like vaccinations. Future confirmatory studies are warranted.

摘要

接种严重急性呼吸综合征冠状病毒2(SARS-CoV-2)疫苗可有效预防重症冠状病毒病(Covid-19),但随着时间推移,其降低病毒载量和传播的效力会减弱。此外,新型SARS-CoV-2变体的出现增加了不受控制传播的威胁,迫切需要额外的抗病毒疗法来有效遏制疫情。此前的研究表明,(该物质)对包括SARS-CoV-2在内的包膜病毒具有强大的抗病毒活性。在本研究中,我们考察了(该物质)在预防和治疗呼吸道感染(RTIs),特别是SARS-CoV-2感染方面的潜力。120名健康志愿者(年龄18 - 75岁,男女不限)被随机分配至预防组或对照组,预防组每日服用2400毫克提取物(紫锥菊制剂,EF),为期2、2和1个月,共3个预防周期,期间无任何干预措施。预防周期被1周的休息时间打断。急性呼吸道症状采用4000毫克EF治疗,最长持续10天,并通过日记评估其严重程度。每月以及在急性疾病期间常规采集鼻咽拭子和静脉血样本,用于通过逆转录-定量聚合酶链反应(RT-qPCR)和血清学检测及鉴定包括SARS-CoV-2在内的呼吸道病毒。汇总预防各阶段的数据,EF组和对照组分别有21份和29份样本检测出任何病毒呈阳性,其中5份和14份样本检测出SARS-CoV-2呈阳性(相对危险度 = 0.37,卡方检验,P = 0.03)。总体而言,两组分别出现10次和14次有症状发作,其中5次和8次为Covid-19(相对危险度 = 0.70,卡方检验,P > 0.05)。在急性发作期间应用EF治疗可使总体病毒载量显著降低至少2.12对数或约99%(t检验,P < 0.05),所有病毒的病毒清除时间缩短8.0天(Wilcoxon检验,P = 0.02),SARS-CoV-2的病毒清除时间缩短4.8天(P > 0.05)。与对照组相比,EF治疗显著减少了发热天数(1天对11天,卡方检验,P = 0.003),但未降低总体症状严重程度。EF治疗组中与Covid-有关的住院人数较少(分别为0例和2例)。EF具有抗病毒作用,可降低包括SARS-CoV-2在内的病毒性呼吸道感染的风险。通过大幅降低感染个体的病毒载量,EF为如疫苗接种等现有的法定治疗提供了辅助支持。未来需要进行确证性研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7db0/9087554/99430a693b07/fphar-13-856410-g001.jpg

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