Objectives
The Bacillus Calmette-Guérin (BCG) vaccine may induce non-specific protection against unrelated infections. We tested the effect of BCG on the risk of infections among Danish senior citizens.
Methods
Single-blinded randomised controlled trial including 1676 volunteers >65 years. Participants were randomised 1:1 to BCG or placebo and followed for 12 months. The primary outcome was acute infection leading to medical contact. Secondary outcomes were verified SARS-CoV-2 infection, self-reported respiratory symptoms, and all-cause hospitalisation. Data was analysed using Cox regression models, estimating hazard ratios (HR) with 95% confidence intervals (CI).
Results
The incidence of acute infection was 52.1 and 58.2 per 100 person-years for BCG and placebo, respectively (HR=0.89, 95% CI=0.78–1.02). There was no effect of BCG on SARS-CoV-2 infections (0.97, 0.75–1.26) or all-cause hospitalisations (1.10, 0.80–1.50), but BCG was associated with more respiratory symptoms (1.21, 1.10–1.33). BCG reduced the incidence of acute infections among participants <75 years (0.82, 0.70–0.95) but not among those >75 years (1.14, 0.88–1.47). In participants, who were COVID-19 vaccinated before enrolment, BCG was associated with lower incidence of acute infections (0.65, 0.50–0.85).
Conclusion
BCG did not reduce risk of acute infections among Danish seniors overall, but the effect was modified by age group and COVID-19 vaccination.
Trial registration
ClinicalTrials.gov (NCT04542330) and EU Clinical Trials Register (EudraCT number 2020-003904-15). Full trial protocol is available at ClinicalTrials.gov.
Summary
In a randomised clinical trial among Danish senior citizens, BCG vaccination did not reduce the overall risk of acute infection, but BCG was associated with reduced risk in participants <75 years and participants who received COVID-19 vaccines prior to enrolment.