The Effect of BCG Vaccination in the Elderly on Infectious and Non-Infectious Immune-Mediated Diseases

Elisabeth A. Dulfer; Konstantin Föhse; Esther Taks; Simone J.C.F.M. Moorlag; Eva L. Koekenbier; Josephine 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

doi:10.1016/j.jinf.2024.106344

Abstract

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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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