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

Abstract

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.

Keywords: BCG revaccination; BCG vaccine; COVID-19 pandemic; Heterologous effects; Infectious diseases; Non-specific effects of vaccines; Randomised controlled trial; Senior citizens.