The effect of BCG vaccination in the elderly on infectious and non-infectious immune-mediated diseases

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES Journal of Infection Pub Date : 2024-11-06 DOI:10.1016/j.jinf.2024.106344

Elisabeth A. Dulfer , Konstantin Föhse , Esther J.M. Taks , Simone J.C.F.M. Moorlag , Eva L. Koekenbier , Josephine S. van de Maat , Jaap ten Oever , Jacobien J. Hoogerwerf , Cornelis H. van Werkhoven , Marc J.M. Bonten , Astrid van Hylckama Vlieg , Frits R. Rosendaal , Mihai G. Netea

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Abstract

Objectives

Previous research has suggested beneficial heterologous effects of the Bacillus Calmette-Guérin (BCG) vaccine on non-mycobacterial infections and other immune-mediated diseases. During the COVID-19 pandemic, randomized controlled trials BCG-PRIME (n = 5349) and BCG-CORONA-ELDERLY (n = 1907) investigated the impact of BCG on SARS-CoV-2 infections in older individuals. We extended the follow-up in these studies by one year (BCG-Long Term study), to assess the overall effects of BCG vaccination on infectious and immune-mediated diseases in individuals aged over 60.

Methods

Prior participants were invited to complete a one-year follow-up survey after their completion of the original trial. Data on vaccinations, hospital admissions, infectious episodes, and new medical diagnoses were collected and compared between BCG- and placebo-vaccinated participants. Variables of interest were combined with the previous trial databases and analyzed using relative risks (RR) and an adjusted Cox regression model accounting for participation probability.

Results

The response in the follow-up survey was 60%, including 4238 individuals in the final analysis (2317 had received BCG and 1921 placebo). Incidence and severity of infectious diseases and other diagnoses, including cardiovascular diseases and cancer, did not differ between the groups. The proportion of individuals hospitalized for cardiac arrhythmias after BCG was two-fold higher than reported after placebo (1.6% versus 0.8%, RR 2.0 (95% confidence interval 1.1–3.6)). Cardiac arrhythmia-related hospitalizations were primarily due to exacerbation of pre-existing arrhythmias.

Conclusion

The results of the present study confirm that BCG has no relevant effect on non-mycobacterial infectious diseases and other immune-mediated diseases in a population of generally mycobacteria-naïve older Dutch individuals in the two years following vaccination. However, our study suggests that BCG may aggravate pre-existing cardiac arrhythmia, which warrants further investigation.

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老年人接种卡介苗对传染性和非传染性免疫介导疾病的影响。

目的：以往的研究表明，卡介苗（BCG）对非霉菌感染和其他免疫介导疾病具有有益的异源效应。在 COVID-19 大流行期间，随机对照试验 BCG-PRIME（n = 5349）和 BCG-CORONA-ELDERLY（n = 1907）调查了卡介苗对老年人 SARS-CoV-2 感染的影响。我们将这些研究的随访时间延长了一年（卡介苗长期研究），以评估卡介苗接种对 60 岁以上人群感染性疾病和免疫介导性疾病的总体影响：方法：邀请先前的参与者在完成原始试验后完成为期一年的跟踪调查。我们收集了接种疫苗、入院、传染病发作和新诊断的数据，并对接种卡介苗和接种安慰剂的参与者进行了比较。相关变量与之前的试验数据库相结合，使用相对风险系数（RR）和调整后的考克斯回归模型（考虑参与概率）进行分析：后续调查的回复率为 60%，最终分析包括 4238 人（2317 人接受过卡介苗，1921 人接受过安慰剂）。两组间传染病和其他诊断（包括心血管疾病和癌症）的发病率和严重程度没有差异。卡介苗治疗后因心律失常住院的比例是安慰剂治疗后的两倍（1.6% 对 0.8%，RR 2.0（95% 置信区间 1.1-3.6））。与心律失常相关的住院治疗主要是由于原有心律失常的加重：本研究结果证实，在接种卡介苗后的两年内，卡介苗对非分枝杆菌感染性疾病和其他免疫介导性疾病没有相关影响。不过，我们的研究表明，卡介苗可能会加重原有的心律失常，这值得进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Infection 医学-传染病学

CiteScore

45.90

自引率

3.20%

发文量

475

审稿时长

16 days

期刊介绍： The Journal of Infection publishes original papers on all aspects of infection - clinical, microbiological and epidemiological. The Journal seeks to bring together knowledge from all specialties involved in infection research and clinical practice, and present the best work in the ever-changing field of infection. Each issue brings you Editorials that describe current or controversial topics of interest, high quality Reviews to keep you in touch with the latest developments in specific fields of interest, an Epidemiology section reporting studies in the hospital and the general community, and a lively correspondence section.