The effect of BCG vaccination on adult mortality during the COVID-19 pandemic: a meta-analysis of randomised controlled trials

ObjectivesBacillus Calmette-Guerin (BCG), similar to some other live vaccines, may offer partial protection against unrelated infections. During the COVID-19 pandemic, several trials tested whether BCG provides protection against COVID-19. DesignMeta-analysis of randomised placebo-controlled trials which provided mortality data. SettingHigh-income settings as well as low- and middle-income settings (LMICs). ParticipantsTrial populations were healthcare workers (HCW) or individuals of older age, followed for 6-12 months. InterventionsBCG vaccine versus placebo. Main outcome measureOverall mortality and COVID-19 mortality. ResultsNine of the 15 RCTs reported at least one death. Trial populations were healthcare workers (4 RCTs) or individuals of older age (5 RCTs), in Europe (5 RCTs) or LMICs (4 RCTs) with a total of 8,169 participants randomly allocated to BCG (18 deaths) and 8,176 to placebo (37 deaths). In a meta-analysis, receiving BCG vs placebo was associated with a 51% (95% CI: 15 to72%) reduction in all-cause mortality. The all-cause mortality RRR was 78% (-3 to 95%) in HCWs (Europe and LMICs) and 43% (95% CI: -6 to 69%) in the elderly. It was 37% (95 CI: -15 to 66%) in Europe and 90% (95% CI: 22 to 99%) in LMICs. The relative reduction of deaths (6 BCG; 12 placebo) from COVID-19 was 50% (95 CI: -33 to 81). ConclusionsBCG may have reduced all-cause mortality in the context of the COVID-19 pandemic.