Abstract

Despite the implementation of mitigation measures, Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still spreading worldwide, and has caused more than 1 million deaths so far. Although recent reports indicate that three vaccine candidates are effective against SARS-CoV-2, more time is needed to generate enough doses for the general population. Meanwhile, frontline healthcare workers are at high risk of SARS-CoV-2 exposure. To avoid collapse of the medical care system, there is a need to develop novel approaches to limit SARS-CoV-2 spread. Through a process called trained immunity, the Bacillus Calmette-Guerin (BCG) vaccine boosts the action of innate immune cells, resulting in a nonspecific reduction in the incidence of viral infections. Due to this immunomodulatory action, the BCG vaccine is currently used as a therapeutic in bladder cancer. Data collected from epidemiological and observational studies indicate that BCG vaccination might provide protection against COVID-19. While these observations do not provide evidence of causality and are limited by cofounding and intrinsic biases, it is crucial to explore the hypothesis that BCG vaccination may provide a nonspecific innate immune boost and therefore protect against COVID-19 in randomized controlled clinical trials, particularly for people at higher risk of developing COVID-19, such as frontline healthcare workers.

中文翻译：

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调查卡介苗预防潜在COVID-19感染的随机临床试验的基本原理

摘要

尽管已采取缓解措施，但由严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）引起的冠状病毒病2019（COVID-19）仍在全球范围内传播，迄今已造成100万人死亡。尽管最近的报告表明三种候选疫苗可有效抵抗SARS-CoV-2，但仍需要更多时间为普通人群产生足够的剂量。同时，一线医护人员面临SARS-CoV-2暴露的高风险。为了避免医疗保健系统崩溃，需要开发新的方法来限制SARS-CoV-2传播。通过称为“免疫训练”的过程，卡介苗芽孢杆菌（BCG）疫苗可增强先天免疫细胞的作用，从而非特异性地减少了病毒感染的发生率。由于这种免疫调节作用，BCG疫苗目前被用作膀胱癌的治疗剂。从流行病学和观察性研究中收集的数据表明，接种卡介苗可能会预防COVID-19。尽管这些观察结果没有提供因果关系的证据，并且受到共同创立和内在偏见的限制，但至关重要的是要探索以下假设：卡介苗接种可能会提供非特异性的先天免疫增强作用，从而在随机对照临床试验中针对COVID-19提供保护，尤其是对于一线医护人员等罹患COVID-19的风险较高的人。