100 years of Bacillus Calmette-Guérin immunotherapy: from cattle to COVID-19.

Bacillus Calmette-Guérin (BCG) is the most widely used vaccine worldwide and has been used to prevent tuberculosis for a century. BCG also stimulates an anti-tumour immune response, which urologists have harnessed for the treatment of non-muscle-invasive bladder cancer. A growing body of evidence indicates that BCG offers protection against various non-mycobacterial and viral infections. The non-specific effects of BCG occur via the induction of trained immunity and form the basis for the hypothesis that BCG vaccination could be used to protect against the severity of coronavirus disease 2019 (COVID-19). This Perspective article highlights key milestones in the 100-year history of BCG and projects its potential role in the COVID-19 pandemic.

The association of Coronavirus Disease-19 mortality and prior bacille Calmette-Guerin vaccination: a robust ecological analysis using unsupervised machine learning.

Population-level data have suggested that bacille Calmette-Guerin (BCG) vaccination may lessen the severity of Coronavirus Disease-19 (COVID-19) prompting clinical trials in this area. Some reports have demonstrated conflicting results. We performed a robust, ecologic analysis comparing COVID-19 related mortality (CRM) between strictly selected countries based on BCG vaccination program status utilizing publicly available databases and machine learning methods to define the association between active BCG vaccination programs and CRM. Validation was performed using linear regression and country-specific modeling. CRM was lower for the majority of countries with a BCG vaccination policy for at least the preceding 15 years (BCG15). CRM increased significantly for each increase in the percent population over age 65. A higher total population of a country and BCG15 were significantly associated with improved CRM. There was a consistent association between countries with a BCG vaccination for the preceding 15 years, but not other vaccination programs, and CRM. BCG vaccination programs continued to be associated with decreased CRM even for populations < 40 years old where CRM events are less frequent.

The role of the urologist, BCG vaccine administration, and SARS-CoV-2: An overview.

OBJECTIVES: To summarize the available literature regarding bacillus Calmette-Guerin (BCG) administration, severe acute respiratory syndrome conoravirus-2 (SARS-CoV-2), and the resulting clinical condition coronavirus disease (COVID-19) in light of recent epidemiologic work suggesting decreased infection severity in BCG immunized populations while highlighting the potential role of the urologist in clinical trials and ongoing research efforts. MATERIALS AND METHODS: We reviewed the available literature regarding COVID-19 and BCG vaccination. Specifically, the epidemiologic evidence for decreased COVID-19 morbidity in countries with BCG vaccination programs, current clinical trials for BCG vaccination to protect against COVID-19, potential mechanisms and rationale for this protection, and the role of the urologist and urology clinic in providing support and/or leading ongoing efforts. RESULTS: Epidemiologic evidence suggests that the crude case fatality rates are lower for countries with BCG vaccination compared to those without such programs. Four prospective, randomized clinical trials for BCG vaccination were identified including NCT04348370 (BADAS), NCT04327206 (BRACE), NCT04328441 (BCG-CORONA), and NCT04350931. BCG administration may contribute to innate and adaptive immune priming with several opportunities for translational research. CONCLUSIONS: The urologist's expertise with BCG and the infrastructure of urologic clinics may afford several opportunities for collaboration and leadership to evaluate and understand the potential role of BCG in the current COVID-19 pandemic.