Why Tuberculosis May Protect Against COVID-19

Courtesy Harvard HSPH
Courtesy Harvard HSPH

Though the worst of the COVID-19 pandemic (possibly? hopefully?) may be behind us, so too might be our immunity to the virus, whether it’s through vaccination or through natural infection. In February, the CDC announced that while vaccine boosters were 91 percent effective in preventing hospitalization after two months, that number slipped to 78 percent after four months. The jury is still out on whether a fourth booster is necessary.

As this plays out, a bizarre yet interesting wrinkle has emerged: tuberculosis infection somehow prevents coronavirus infection. In a new study published Thursday in the journal PLOS Pathogens, researchers at the Ohio State University found that mice infected with the bacteria that causes tuberculosis were resistant to falling sick after exposure to the alpha variant of COVID.

“This research might explain why some [people] have never gotten COVID,” Dr. Shira Doron, a hospital epidemiologist at Tufts Medical Center who was not part of the study, told The Daily Beast. “[And whether] there are any treatments or preventative measures we could leverage.”

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During the pandemic, scientists have noticed an interesting trend: Countries in the developing world with endemic infections like tuberculosis seem to experience fewer COVID-related deaths, Dr. William Bishai, an infectious disease specialist at Johns Hopkins University School of Medicine who was not a part of the study, told The Daily Beast. “Perhaps it’s due to a pre-existing exposure to tuberculosis that confers some degree of immunity against COVID-19.”

The Ohio State University researchers sought to understand whether this was truly the case. They took one ordinary mouse commonly used in lab experiments and another that’s been genetically altered to carry the human version of ACE2, the receptor used by the coronavirus to enter our cells. These mice were both infected with an active form of tuberculosis that can very quickly lead to illness. A month after tuberculosis infection, the researchers then exposed the mice to COVID.

“We initially predicted we would give the animals [COVID] and they would go downhill,” Richard Robinson, a microbiologist at the Ohio State University who led the new study, told The Daily Beast. But the mice didn’t show any signs of weight loss—which scientists use as an indicator of infection in mice—and their health did not significantly differ from other TB-infected mice not exposed to COVID.

It’s not entirely clear why tuberculosis acts as some sort of COVID firewall. Robinson said one theory is that tuberculosis causes so much inflammation in the lung, the virus might have a hard time finding a way in. “Your lungs are like ‘Whoa, whoa, whoa,’ there’s already enough of a toxic environment for a virus that it inhibits it,” he said.

But another theory is that somehow, tuberculosis primes our immune system against the coronavirus. The COVID-exposed mice were chock full of T-cells (which are important in fighting bacterial infections) as well as B cells (which make antibodies). Though tuberculosis and COVID don’t really share any similarities when it comes to their infectious proteins, what might be happening is a phenomenon called trained immunity.

“Tuberculosis is a human disease, it’s co-evolved with us over thousands of years,” said Bishai, whose lab at Johns Hopkins studies tuberculosis. “Why hasn’t it killed off humanity or been overcome? One idea is that by getting exposed to tuberculosis, the immune system gets trained and that makes humans more resistant to dangerous viral infections.”

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If that’s the case with COVID, Bishai and Doron suggested we might want to consider vaccinating ourselves with the BCG vaccine, the only shot that targets tuberculosis by using a milder, weaker strain of the bacteria.

“This is a vaccine that we don’t use in the U.S. but in many parts of the world, it’s used to prevent tuberculosis,” Doron said. “There’s recent epidemiologic studies suggesting that the BCG vaccine could protect against COVID.”

While this new study comes right at a crucial time as we’re figuring out long-term ways to keep COVID at bay, these findings are only based on mice. We would need to see the science hold up in different animal models and for different variants of the virus (only the alpha variant was tested in this study) before getting to even just a preliminary investigation in humans.

“This study may explain why there’s such great variation in COVID infection and maybe why tuberculosis infection confers some resistance to COVID,” Robinson said. “But this study is not a reason to think you won’t get COVID or should not get vaccinated against COVID.”

Exactly, dear reader. Please don’t try to get tuberculosis—it’s much safer to just get vaccinated.

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