Evaluating the effect of BCG vaccination for non-specific protection from infection in senior citizens during the COVID-19 pandemic:A randomised clinical trial
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. 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.</p
