Several months ago, an interesting correlation emerged: countries that had a mandatory BCG vaccine for tuberculosis seemed to have lower mortality rates from the coronavirus.

Some researchers interpreted this as a potential protective effect offered by the vaccine, while others only saw it only as a “shred of evidence.” Now, a peer-reviewed study adds more evidence to the idea that the tuberculosis vaccine could help protect against COVID-19.

It’s already been over half a year since mankind started battling the dreaded novel coronavirus — and the fight is far from over. But, as time passes, we are at least learning more and more about the virus and how we can become more resistant against it.

We’re dealing with a very unusual pathogen and in many ways, it’s not behaving as we anticipated. For instance, it’s puzzling why some developing countries seem to have lower mortality rates than some developed countries, which presumably have better health systems.

There are several differences that could help explain that discrepancy (such as lower average age or simply that developing countries are doing a poorer job at data gathering), but one theory suggests something else might also be at play: the BCG vaccine, used against tuberculosis.

The BCG vaccine was first introduced in 1921, and it is now on the World Health Organization’s List of Essential Medicines, a list of the ‘safest and most effective medicines’ needed in a society. The BCG vaccine is no longer prevalent in the developed world, however, because tuberculosis itself is not that prevalent in the developed world. That may play a role in the COVID-19 pandemic, a group of researchers says.

“In our initial research, we found that countries with high rates of BCG vaccinations had lower rates of mortality,” explained Escobar, an affiliate of the Global Change Center housed in the Fralin Life Sciences Institute. “But all countries are different: Guatemala has a younger population than, say, Italy, so we had to make adjustments to the data to accommodate those differences.”

Working with NIH researchers, Escobar collected coronavirus mortality data from around the world. The team then adjusted that data for relevant variables such as population density, age, income, and access to health services. Even after they controlled for all these variables, the correlation still stands: countries with higher rates of BCG vaccinations have lower peak mortality rates from COVID-19.

Strikingly, Germany seems to offer good support for this theory, a separate study finds. Prior to the country’s unification in 1990, West Germany and East Germany had different BCG vaccinations. West Germany provided BCG vaccines from 1961 to 1998, while East Germany started earlier, but stopped in 1975. This implies that older Germans in former East Germany would have more protection than their western peers — and this is exactly what recent data has shown: western German states have mortality rates that are 2.9 times higher than those in eastern Germany.

It’s also not entirely surprising that the BCG vaccine would offer such protection. There is systematic review evidence showing that BCG vaccination prevents respiratory infections (pneumonia and influenza) in children and the elderly. BCG has also been shown to provide broad cross-protection from a number of viral respiratory illnesses in addition to tuberculosis, so it’s reasonable that it could do the same for COVID-19.

“The purpose of using the BCG vaccine to protect from severe COVID-19 would be to stimulate a broad, innate, rapid-response immunity,” said Escobar.

However, Escobar stresses that this is still preliminary research, and more work is still needed to validate the results. If confirmed, it would also be necessary to assess just how strong this protective effect is, and how this could (perhaps) be used to our advantage.

“We’re not looking to advise policy with this paper,” Escobar said. “This is, instead, a call for more research. We need to see if we can replicate this in experiments and, potentially, in clinical trials. We also need to come back to the data as we get more information, so we can reevaluate our understanding of the coronavirus pandemic.”

Researchers also caution against stockpiling BCG vaccines, which we’ve already seen happening in the case of hydroxychloroquine.

For now, this remains a noteworthy idea that warrants further investigation. There are already clinical trials underway to assess if and how BCG vaccination in adults can also confer protection from severe COVID-19.

The study is set for publication in PNAS.