A preliminary study finds a potential ally against COVID-19: the TB vaccine.

COVID-19 has spread to most of the world and continues to spread farther and farther. However, the impact of the disease can vary significantly from area to area. Much of this can be attributed to societal factors (such as average age, smoking rates, rate of underlying health issues) or to the performance of national health systems. But another factor, some researchers propose, has to do with vaccination — TB vaccination, to be exact.

The study published on medRxiv (a site for preliminary medical research) finds an intriguing correlation between countries that require people to get the Bacillus Calmette-Guerin (BCG) vaccine and those showing fewer numbers of confirmed cases and deaths from COVID-19.

Lead author Gonzalo Otazu, assistant professor at the New York Institute of Technology, says he was surprised by the relatively low number of cases in Japan — a country with an older population and which has not taken the strict quarantine measures imposed in many other parts of the world.

Japan has had a policy of universal BCG vaccination of infants against tuberculosis (TB) since 1951. Otazu and colleagues then inspected several other countries, assessing how the presence of a BCG vaccination correlates with COVID-19 severity.

According to their analysis, if a population is vaccinated against TB, it has better odds of faring better against the coronavirus.

“We found that countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies,” the study authors explain.

‘It’s like the BCG vaccine creates bookmarks for the immune system to use later’, Otazy commented. The correlation was also observed in countries that introduced the vaccine later on (and in which the elderly population is unvaccinated and therefore more vulnerable).

“Countries that have a late start of universal BCG policy (Iran, 1984) had high mortality, consistent with the idea that BCG protects the vaccinated elderly population.”

A “weird” vaccine

It’s not entirely surprising that a vaccine against one pathogen would offer partial protection against others. The BCG vaccine, in particular, interacts with the human body in a complex way which is not fully understood.

As far as approved vaccines go (and the BCG has been approved for almost a century), it’s one of the weirder ones. A 1994 systematic review found that BCG reduces the risk of getting TB by about 50%, with its efficacy varying significantly based on genetic factors. The BCG vaccine is also used against leprosy and some ulcerations. Remarkably, the vaccine has also become a key treatment against bladder cancer. According to one study, BCG is “the standard of care for patients with bladder cancer (NMIBC)” since 1977.

Notably, it’s not currently in use in many countries (notably the US and developed countries in Europe). It is, however, still mandatory in developed countries such as Japan and South Korea — both of which have had a remarkable track record against COVID-19.

Reactions from researchers on this preliminary study have been mixed. Some have criticized the correlation as speculative, which Otazu says he will address in a revised version of the study. The authors also emphasize that most data on confirmed cases from low-income countries were considered not reliable enough to make a strong judgment, and only reliable data was used.

However, it’s quite possible that the researchers are onto something here. It is probably not coincidental that several clinical trials are already investigating this avenue in the US, UK, Germany, and Denmark.

Perhaps the most intriguing of these clinical trials is carried out by Mihai Netea, an infectious-disease expert at Radboud University Medical Center in the Netherlands. Netea and his team enrolled 400 health workers in the trial, 200 of whom were administered the BCG vaccine, while the other 200 got a placebo. It will be 2 months or even more before the first results start coming in, but Netea is already working on a separate trial to study the effectiveness of the vaccine on people over 60.

It’s hard to say that exactly in what way the vaccine can protect against the coronavirus, particularly as TB is caused by bacteria, not a virus. It could be that the TB bacteria and the coronavirus use a similar attack strategy on the human body, which the vaccine offers some protection against.

For now, it’s hard to say just how effective the BCG vaccine is against COVID-19 — or even if it is effective at all. But it’s an interesting avenue worth researching.