Introduction: The bacille Calmette-Guerin (BCG) vaccine is used for the prevention of tuberculosis (TB) worldwide. Evidence reports a much lower incidence of COVID-19 in TB-endemic areas implying a possible protective mechanism of BCG in countries with mandated BCG policies. The objective of the study is to synthesize and critically evaluate the effectiveness of national BCG vaccination policies in reducing infection and severity of COVID-19 in their native population.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive search using pre-identified keywords will be done in PubMed, Cochrane, HERDIN Plus, WPRIM, Web of Science and EBSCO databases. After the initial selection of studies based on eligibility criteria, methodological appraisal will be conducted using the Joanna Briggs Institute appraisal instruments and an adapted quality assessment checklist for ecologic studies. Relevant data will be extracted and synthesized including reporting descriptive and inferential statistics to interpret results.

Results: The study will generate a systematic review synthesizing evidence regarding the effects of BCG in curtailing the spread of the COVID-19 pandemic.

Discussion: The battle against the COVID-19 pandemic is far from over, and as such, further studies must be undertaken to verify the evidence behind initial strategies in battling it. This includes the use of BCG in decreasing COVID-19 incidence and mortality. The results of the review can ultimately guide health authorities and policy makers create evidence-based decisions regarding BCG vaccination policies and clinical trials related to COVID-19 control and prevention.

Systematic Review Registration: PROSPERO, CRD42021244060