BCG 疫苗对 2019 冠状病毒病大流行期间老年人呼吸道感染的疗效。
Efficacy of BCG Vaccination Against Respiratory Tract Infections in Older Adults During the Coronavirus Disease 2019 Pandemic.
机构信息
Department of Internal Medicine Radboud University Medical Center, Nijmegen, the Netherlands.
Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
出版信息
Clin Infect Dis. 2022 Aug 24;75(1):e938-e946. doi: 10.1093/cid/ciac182.
BACKGROUND
Older age is associated with increased severity and death from respiratory infections, including coronavirus disease 2019 (COVID-19). The tuberculosis BCG vaccine may provide heterologous protection against nontuberculous infections and has been proposed as a potential preventive strategy against COVID-19.
METHODS
In this multicenter, placebo-controlled trial, we randomly assigned older adults (aged ≥60 years; n = 2014) to intracutaneous vaccination with BCG vaccine (n = 1008) or placebo (n = 1006). The primary end point was the cumulative incidence of respiratory tract infections (RTIs) that required medical intervention, during 12 months of follow-up. Secondary end points included the incidence of COVID-19, and the effect of BCG vaccination on the cellular and humoral immune responses.
RESULTS
The cumulative incidence of RTIs requiring medical intervention was 0.029 in the BCG-vaccinated group and 0.024 in the control group (subdistribution hazard ratio, 1.26 [98.2% confidence interval, .65-2.44]). In the BCG vaccine and placebo groups, 51 and 48 individuals, respectively tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with polymerase chain reaction (subdistribution hazard ratio, 1.053 [95% confidence interval, .71-1.56]). No difference was observed in the frequency of adverse events. BCG vaccination was associated with enhanced cytokine responses after influenza, and also partially associated after SARS-CoV-2 stimulation. In patients diagnosed with COVID-19, antibody responses after infection were significantly stronger if the volunteers had previously received BCG vaccine.
CONCLUSIONS
BCG vaccination had no effect on the incidence of RTIs, including SARS-CoV-2 infection, in older adult volunteers. However, it improved cytokine responses stimulated by influenza and SARS-CoV-2 and induced stronger antibody titers after COVID-19 infection.
CLINICAL TRIALS REGISTRATION
EU Clinical Trials Register 2020-001591-15 ClinicalTrials.gov NCT04417335.
背景
年龄增长与呼吸道感染（包括 2019 年冠状病毒病[COVID-19]）的严重程度和死亡率升高相关。结核分枝杆菌卡介苗（BCG）疫苗可能对非结核感染提供异源保护作用，并被提议作为预防 COVID-19 的一种潜在策略。
方法
在这项多中心、安慰剂对照试验中，我们将年龄≥60 岁的老年人（n=2014）随机分配至接受 BCG 疫苗（n=1008）或安慰剂（n=1006）皮内接种。主要终点是 12 个月随访期间需要医疗干预的呼吸道感染（RTI）的累积发生率。次要终点包括 COVID-19 的发生率，以及 BCG 疫苗接种对细胞和体液免疫反应的影响。
结果
BCG 疫苗接种组的 RTI 需要医疗干预的累积发生率为 0.029，对照组为 0.024（亚分布风险比，1.26[98.2%置信区间，0.65-2.44]）。在 BCG 疫苗组和安慰剂组中，分别有 51 人和 48 人经聚合酶链反应检测到严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）阳性（亚分布风险比，1.053[95%置信区间，0.71-1.56]）。未观察到不良事件的频率存在差异。BCG 疫苗接种与流感后细胞因子反应增强相关，与 SARS-CoV-2 刺激后也部分相关。在诊断为 COVID-19 的患者中，如果志愿者先前接受过 BCG 疫苗接种，感染后抗体反应明显更强。
结论
BCG 疫苗接种对老年志愿者的 RTI 发生率（包括 SARS-CoV-2 感染）没有影响。然而，它改善了流感和 SARS-CoV-2 刺激后的细胞因子反应，并在 COVID-19 感染后诱导了更强的抗体滴度。
临床试验注册
欧盟临床试验注册 2020-001591-15；ClinicalTrials.gov NCT04417335。
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