Effectiveness of Bacille Calmette-Guerin vaccination policies in reducing infection and mortality of COVID-19: a systematic review

Abstract Background COVID-19 vaccination has been advocated as the most effective way to curb the pandemic. But with its inequitable distribution and slow rollout, especially in low- to middle- income countries, it will still take a long time before herd immunity is achieved. Alternative measures must therefore be explored to bolster current COVID-19 vaccination efforts. In particular, the Bacille Calmette-Guerin vaccine has been studied extensively as to its proposed conferment of non-specific immunity against different infections, including COVID-19. The aim of this study, therefore, is to evaluate the current evidence on the effectiveness of national BCG vaccination policies in reducing infection and mortality of COVID-19. Methods A systematic review was conducted between April to August 2021 following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA-P) guidelines. Literature was retrieved from PubMed, Cochrane, HERDIN, Web of Science, EBSCO, and Western Pacific Region Index Medicus (WPRIM). Studies conducted from January 2020 to August 2021 that fell within Level 1A to 2C of the Oxford Center for Evidence-Based Medicine were included in the review. Quality assessment was performed using the appropriate Joanna Briggs Institute critical appraisal tool and a quality assessment checklist for ecological studies adapted from Betran et al. Results A total of 13 studies were included in this review. Nine studies reported significant association between BCG vaccination policies and COVID-19 outcomes, even when controlling for confounding variables. In addition, among other mandated vaccines, such as pneumococcal, influenza, diphtheria-tetanus-pertussis, and measles, only BCG vaccination showed significant association with decreased COVID-19 adverse outcomes. However, other factors also showed positive association with COVID-19 outcomes, particularly markers of high economic status of countries, higher median age, and greater population densities. Conclusion The lower incidence and mortality of COVID-19 in countries with mandated BCG vaccination may not solely be attributable to BCG vaccination policies, but there is still some evidence that demonstrates a possible protective effect. Clinical trials must be continued before recommendations of BCG vaccinations are to be used as an alternative or booster vaccine against COVID-19.