Considering the therapeutic potential of honey and Nigella sativa (HNS) in coronavirus disease 2019 (COVID-19) patients, the objective of the study is defined to evaluate the prophylactic role of HNS. The study is a randomized, placebo-controlled, adaptive clinical trial with parallel group design, superiority framework with an allocation ratio of 1:1 among experimental (HNS) and placebo group. An interim analysis will be done when half of the patients have been recruited to evaluate the need to adapt sample size, efficacy, and futility of the trial. All asymptomatic patients with hospital or community based COVID-19 exposure will be screened if they have had 4 days exposure to a confirmed case. Non-pregnant adults with significant exposure level will be enrolled in the study Subjects with acute or chronic infection, COVID-19 vaccinated, and allergy to HNS will be excluded from the study. Recruitment will be done at Shaikh Zayed Post-Graduate Medical Institute, Ali Clinic and Doctors Lounge in Lahore (Pakistan). In this clinical study, patients will receive either raw natural honey (0.5 g) and encapsulated organic Nigella sativa seeds (40 mg) per kg body weight per day or empty capsule with and 30 ml of 5% dextrose water as a placebo for 14 days. Both the natural products will be certified for standardization by Government College University (Botany department). Furthermore, each patient will be given standard care therapy according to version 3.0 of the COVID-19 clinical management guidelines by the Ministry of National Health Services of Pakistan. Primary outcome will be Incidence of COVID-19 cases within 14 days of randomisation. Secondary endpoints include incidence of COVID-19-related symptoms, hospitalizations, and deaths along with the severity of COVID-19-related symptoms till 14th day of randomization. Participants will be randomized into experimental and control groups (1:1 allocation ratio) via the lottery method. There will be stratification based on high risk and moderate risk exposure. Quadruple blinding will be ensured for the participants, care providers and outcome accessors. Data analysts will also be blinded to avoid conflict of interest. Site principal investigator will be responsible for ensuring masking. 1000 participants will be enrolled in the study with 1:1 allocation. The final protocol version 1.4 was approved by institutional review board of Shaikh Zayed Post-Graduate Medical Complex on February 15, 2021. The trial recruitment was started on March 05, 2021, with a trial completion date of February 15, 2022. Clinical trial was registered on February 23, 2021, www.clinicaltrials.gov with registration ID NCT04767087 . The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). With the intention of expediting dissemination of this trial, the conventional formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.

中文翻译：

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蜂蜜和 Nigella sativa L. 对医院和社区 SARS-CoV-2 传播的预防潜力：随机对照试验研究方案的结构化摘要

考虑到蜂蜜和黑种草 (HNS) 在 2019 年冠状病毒病 (COVID-19) 患者中的治疗潜力，该研究的目标被定义为评估 HNS 的预防作用。该研究是一项随机、安慰剂对照、适应性临床试验，具有平行组设计、优越性框架，实验组（HNS）和安慰剂组之间的分配比为 1:1。当招募了一半的患者以评估调整样本量、疗效和试验无效性的需要时，将进行中期分析。所有在医院或社区接触过 COVID-19 的无症状患者，如果他们与确诊病例接触了 4 天，则将接受筛查。具有显着暴露水平的非怀孕成人将被纳入研究对象患有急性或慢性感染，接种过 COVID-19，并且对 HNS 过敏将被排除在研究之外。招聘将在拉合尔（巴基斯坦）的谢赫扎耶德研究生医学院、阿里诊所和医生休息室进行。在这项临床研究中，患者每天每公斤体重将接受生天然蜂蜜（0.5 克）和封装的有机黑种草种子（40 毫克）或空胶囊和 30 毫升 5% 葡萄糖水作为安慰剂，为期 14 天. 这两种天然产品都将通过政府学院大学（植物学系）的标准化认证。此外，将根据巴基斯坦国家卫生服务部的 COVID-19 临床管理指南 3.0 版为每位患者提供标准护理治疗。主要结果将是随机分组后 14 天内 COVID-19 病例的发生率。次要终点包括 COVID-19 相关症状的发生率、住院和死亡以及 COVID-19 相关症状的严重程度，直至随机分组的第 14 天。参与者将通过抽签方式随机分为实验组和对照组（1:1分配比例）。将根据高风险和中等风险暴露进行分层。将确保参与者、护理提供者和结果访问者采用四盲法。数据分析师也将被蒙蔽以避免利益冲突。现场首席调查员将负责确保掩蔽。1000 名参与者将以 1:1 的比例参加该研究。最终方案 1.4 版于 2021 年 2 月 15 日由谢赫扎耶德研究生医疗综合体的机构审查委员会批准。试验招募于2021年3月5日开始，试验完成日期为2022年2月15日。临床试验于2021年2月23日在www.clinicaltrials.gov注册，注册号为NCT04767087。完整协议作为附加文件附加，可从试验网站访问（附加文件 1）。为了加快该试验的传播，传统的格式已被取消；这封信是对完整协议关键要素的总结。研究方案已根据标准方案项目：临床干预试验建议 (SPIRIT) 指南进行报告。完整协议作为附加文件附加，可从试验网站访问（附加文件 1）。为了加快该试验的传播，传统的格式已被取消；这封信是对完整协议关键要素的总结。研究方案已根据标准方案项目：临床干预试验建议 (SPIRIT) 指南进行报告。完整协议作为附加文件附加，可从试验网站访问（附加文件 1）。为了加快该试验的传播，传统的格式已被取消；这封信是对完整协议关键要素的总结。研究方案已根据标准方案项目：临床干预试验建议 (SPIRIT) 指南进行报告。