Could a Century-Old TB Shot Protect Against Other Respiratory Diseases?

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Three years ago, doctors in Greece began recruiting 198 older people for a unique experiment. They injected half of them with a century-old tuberculosis vaccine typically given to newborns in the developing world. They gave the other half a placebo. They wanted to find out if the vaccine, called Bacillus Calmette–Guérin, or BCG, would protect older people—not against TB, but more broadly against viral infections.

Results are now in: During the year after receiving the shot, the BCG group had 80 percent fewer serious respiratory viral infections than the unvaccinated group. The results were published in Cell at the end of August by doctors at the University of Athens Medical School in Greece, and Radboud University Medical Centre in Nijmegen, Netherlands.

That’s a big deal for a few reasons. People 65 years and older are more likely than any other age group to be hospitalized due to respiratory infections such as influenza, and this study is a preliminary signal that some vaccines could have broad beneficial effects beyond protection from a particular disease. And Covid-19, too, is a respiratory viral illness that disproportionately leads to the hospitalization of older people.

“The chances are increased that BCG would have the same effect on Covid-19 as on other viral respiratory infections like the flu,” says Mihai Netea, the senior author of the study and experimental internal medicine chair at Radboud University. Tests of whether BCG specifically protects against Covid-19 are ongoing; there are now at least 20 randomized clinical trials around the world to see whether it can indeed protect health workers and the elderly.

Many scientists now believe that BCG and some vaccines like it that contain a live, weakened virus may act against non-target diseases. A 2016 review commissioned by the World Health Organization found that BCG and the measles vaccines reduce overall mortality by “more than would be expected through their effects on the diseases they prevent.”

“I think that we have to acknowledge that vaccines have effects much broader than the target disease and the effects can be used,” Netea says.

The research that became the Cell study began in 2017, when Netea’s team recruited patients who were visiting the hospital at the University of Athens Medical School. Most were around 80 years old. They were assigned randomly by computer to either the BCG vaccine or placebo group—the scientists were not aware of the assignments as a nurse injected each patient just before their discharge. This process, called “double-blinding,” is meant to reduce bias. The researchers then rang the patients up every month for a year to check on their health. If a doctor had diagnosed them with an illness, the scientists noted this down.

Netea was nervous about patients having an adverse reaction to the vaccination, itself. In aging patients, there’s always a risk that an immune response can overfire, and BCG has traditionally been given to newborns, not the aged.

Then, Covid-19 hit, and observational studies done by scientists such as Luis Escobar, a disease ecologist at Virginia Tech in Blacksburg, Virginia, hinted that nations where newborns get BCG shots are associated with lower Covid-19 mortality. Netea and his colleagues decided to fast track their analysis. In mid-May, they learned that the vaccinated patients had 80 percent fewer moderate-to-severe respiratory infections.

“That is pretty damn good,” says Kim Mulholland, a vaccinologist at the Murdoch Children’s Research Institute in Melbourne, who was more skeptical of broad beneficial effects of vaccines before this study. “This study left me with the feeling that I should go out and get a BCG vaccine.”

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