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By studying population-level epidemiological trends, researchers have noticed that an old vaccine for tuberculosis may provide some protection against COVID-19.

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As we wait with bated breath for news of progress in developing vaccines for COVID-19, some scientists are turning their attention to vaccines we already have. Only a totally new vaccine, developed to target this tricky new virus, will actually serve to stop it.

But limited evidence is emerging that at least one existing vaccine may play a role in helping to protect us, even though it targets a totally different disease-causing organism. So here's how that might work. The vaccine is BCG, which protects against tuberculosis.

It contains a live, weakened strain of Mycobacterium bovis, a relative of the bacterium that causes most tuberculosis cases in humans. BCG has been around for nearly a century and it's routinely administered to children in parts of the world where tuberculosis poses a significant threat. But it has also been shown to protect against other illnesses, thanks to a phenomenon called trained immunity.

Before the scientific community recognized trained immunity in 2011, they categorized the human immune system in two neat categories — innate and adaptive immunity. In the classical view, the adaptive immune system is the part that remembers specific invaders by creating antibodies against them. Whereas the innate immune system is the nonspecific part that gears up every time an invader shows up in your body, using pretty much the same tools every time to fend them off.

Trained immunity, however, blends those categories. It doesn't help the immune system remember specific pathogens the way the adaptive immune system does. Instead, exposure to some pathogens or vaccines seems to rev up our bodies' bouncers and trigger a state of heightened vigilance that lasts for a while after it deals with that initial challenge.

Scientists have observed a reduction in deaths from maladies like malaria, respiratory illnesses, and even some cancers in people who get BCG as kids, which they think is thanks to that immune training. So… perhaps it could be the case with COVID-19. Some epidemiological research suggests a correlation between certain BCG vaccination programs and lower rates of severe COVID-19 cases.

This kind of research looks at population-level trends; these aren't the results of controlled experiments. However, some scientists have found the potential for trained immunity worthy of a closer look. For example, a study published in July of 2020 in the journal PNAS compared global data on COVID-19 mortality rates.

It found that countries with the highest rates of BCG vaccination had the lowest rate of. COVID-19 deaths for every million people. What's more, average coronavirus death rates in western Europe, where BCG isn't routinely administered, were almost ten times higher than in eastern Europe, where BCG vaccination is still prevalent.

However, they only looked at the first 25 days after a death was reported in a given country. Some countries' death rates have unfortunately caught up since then, which throws off the observed pattern. Another July 2020 study published in Science Advances compared day-by-day increases in confirmed COVID-19 cases and mortality in the first 30 days of outbreaks in over 100 countries.

And it found that countries that mandated BCG vaccination until at least the year 2000 had significantly slower COVID-19 spread compared with those that didn't, at least in the first 30 days of each country's outbreak. Other researchers have pointed out exceptions, though. Australia, for example, ceased mandatory BCG vaccination in the 80s, but has still had a low overall death rate.

Furthermore, there are actually multiple strains of BCG, not all of which may be equally effective in inducing trained immunity. Some of the data seems to indicate that BCG strains that were created earlier are more strongly associated with lower COVID-19 death rates. Just… not all of the data, since Finland and Australia used to use later strains before they stopped giving out BCG, and have lower death rates too.

As does Iceland, which never had a mandatory BCG program. Again, these are strictly observations on a population level. These studies don't indicate whether a given person who got BCG is safe from COVID-19.

Neither do they eliminate other factors that could explain the correlation. But trained immunity provides the mechanism for how BCG could be protective -- and we've seen the effect with other diseases. But do not run out and request a BCG vaccination because you saw this video.

For one thing, it seems to work best when given to infants -- not adults or even older children. Like, the authors of the PNAS study observed that there doesn't seem to be a protective effect in places like the United Kingdom, where BCG was given to older children rather than infants. And this isn't actually that surprising because we already know that BCG is iffy at best when it comes to protecting adults from tuberculosis...the thing it was designed to protect against.

But the researchers think the lack of protection could potentially be due to trained immunity waning in the years after the initial boost from BCG -- though other explanations are possible as well. Like, it might really only work if you get it really young. And, as we mentioned, different strains might have different effects.

So that's a lot of ifs and maybes. But it's enough that researchers are willing to take a chance on clinical trials of BCG. We know it's safe to give to people, and only controlled experiments will help us sort through all these maybes.

Several clinical trials are now looking for recruits to help determine whether BCG is a tool that we should be adding to the kit. So while the race to develop a new vaccine continues, it's interesting to know that an old one might come in handy. Thanks for watching this episode of SciShow News, which was brought to you with the help of our President of Space, SR Foxley.

What we do wouldn't be possible without you, so thank you for your continued support. If you'd like to help support SciShow, and maybe even run for cosmic office yourself, check out [♪outro].