On Sept. 29, 2020, In a new Letter, published in PNAS, researchers at La Jolla Institute for Immunology (LJI) re-examined the correlation between BCG vaccination and COVID-19 case severity. Their updated analysis, based on data from the Johns Hopkins University Coronavirus Resource Center, compared mortality data in 51 countries.

The BCG vaccine is given to babies in countries where tuberculosis is common—to protect them from this bacterial infection. One theory, published in the Proceedings of the National Academy of Sciences (PNAS), was that BCG vaccination might train the innate immune system—the body’s first line of defense—to also better respond to the SARS-CoV-2 virus. The study authors, researchers at Virginia Tech and the National Institute of Allergy and Infectious Diseases, emphasized that more research was needed.

The scientists, led by LJI Professor Bjoern Peters, Ph.D., point out that differences in case severity that could be attributed to BCG vaccination were no longer significant as the pandemic continued into August. The researchers show that Bolivia, Panama, Columbia, Peru, Brazil, Mexico and South Africa had the largest increases in COVID-19 deaths as of Aug. 1. These countries also have high BCG coverage.

For the BCG vaccine to provide protection, the immune response to the vaccine would also have needed to last for many years after infancy. The LJI scientists didn’t find evidence to support this idea.

The researchers also took a closer look at COVID-19 mortality in Germany. Older people in Germany’s Eastern states had a lower mortality rate than those in the Western states, and an early study suggested this difference could be because older Germans in the Eastern states were more likely to have received a BCG vaccine as children.

The LJI team suggests a different explanation. They found that tourism trends could account for the mortality differences. They note that the initial spread of infections in the early stage of the pandemic in Germany was fueled by tourists returning from skiing vacations. The percentage of alpine skiers in different German states correlates well with the reported mortality.

Researchers continue to track COVID-19 cases in relation to BCG vaccination rates, and the LJI researchers hope ongoing randomized controlled trials will provide answers to whether bacillus Calmette–Guérin reduces the incidence and severity of COVID-19.