Bacillus Calmette-Guérin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial

ABSTRACT

Objectives To test whether BCG vaccination would reduce the incidence of COVID-19 and other respiratory tract infections in older adults with one or more comorbidities. Methods Community-dwelling adults over 60 years old with one or more underlying comorbidities and no contra-indications for BCG vaccination were randomized 11 to BCG or placebo vaccination and followed for six months. The primary endpoint was self-reported test-confirmed COVID-19 incidence. Secondary endpoints included COVID-19 hospital admissions and clinically relevant RTI (i.e. RTI including but not limited to COVID-19 requiring medical intervention). COVID-19 and clinically relevant RTI episodes were adjudicated. Incidences were compared using Fine and Gray regression, accounting for competing events. Results A total of 6,112 participants with a median age of 69 years (inter-quartile range 65-74) and median of 2 (inter-quartile range 1-3) comorbidities were randomized to BCG (n=3,058) or placebo (n=3,054) vaccination. COVID-19 infections were reported by 129 BCG recipients compared to 115 placebo recipients (hazard ratio (HR) 1.12;95% confidence interval (CI) 0.87-1.44). COVID-19-related hospitalization occurred in 18 BCG and 21 placebo recipients (HR 0.86;95% CI 0.46-1.61). During the study period 13 BCG recipients compared to 18 placebo recipients died (HR 0.71;95% CI 0.35 - 1.43) of which 11 deaths (35%) were COVID-19 related six in the placebo group and five in the BCG group. Clinically relevant RTI was reported by 66 BCG and 72 placebo recipients (HR 0.92;95% CI 0.66-1.28). Conclusion BCG vaccination does not protect older adults with comorbidities against COVID-19, COVID-19 hospitalization or clinically relevant RTI.