100-Year-Old Tuberculosis Vaccine May Protect Against Covid


By Jessica Bartlett

A small study from researchers at Massachusetts General Hospital suggests that a widely used, 100-year-old vaccine for tuberculosis also may offer protection from COVID-19.

The findings, published on Monday and conducted in volunteers with type 1 diabetes, found that the BCG (Bacillus Calmette-Guerin) vaccine was 92 percent effective versus a placebo in protecting against infections.

Patients already had been enrolled in a study looking at BCG in type 1 diabetes when COVID began circulating in early 2020. Researchers quickly established a parallel trial with the same patients to see how effective BCG was in protecting against the new virus.

All 144 trial participants in the diabetes study enrolled in the parallel trial, which was conducted from January 2020 through April 2021, before any of the participants were vaccinated against COVID. Ninety-six patients received the vaccine, while 48 were treated with a placebo.

Of those who received the vaccine, only one tested positive for COVID-19 antibodies in their blood, indicating a previous infection over the 15-month study. Of those treated with a placebo, six tested positive for COVID antibodies.

Andrew DiNardo, assistant professor of infectious disease at Baylor College of Medicine in Houston, who was not involved in the new study, said the results showed that BCG was more effective against COVID than he would have expected. He is conducting his own research on whether BCG can protect health care workers from the virus.

Even though the nation has readily accessible COVID-specific vaccines, DiNardo said those vaccines haven’t been as durable or as protective against breakthrough infections as scientists had initially hoped. The MGH study raises the possibility that BCG could be used in conjunction with COVID vaccines to strengthen immunity, he said.

“Maybe you wouldn’t need a booster as frequently,” he said. “I think now it will be interesting to see if there are additional clinical trials on how the COVID-specific vaccine works in conjunction with BCG vaccines.”

Denise Faustman, associate professor at Harvard Medical School and director of immunobiology at Massachusetts General Hospital, who led the study, said she plans to seek emergency use authorization from the Food and Drug Administration to use BCG in people with type I diabetes to protect them from COVID.

The clinical trial looking at the benefits of BCG in people with diabetes is ongoing. A small, earlier trial showed that adults with type 1 diabetes who received a BCG vaccine had lower blood sugar levels and were able to use less insulin.

BCG, which contains live but weakened bacteria, has been used for more than 100 years to defend against tuberculosis, with 100 million doses of the vaccine given to newborns in 84 percent of the world’s countries. Because TB isn’t common in the United States, children here have never received the vaccine.

The shots are controversial. They don’t completely protect against TB in adults. However, researchers have shown that the vaccine is protective against other related and unrelated diseases, including leprosy and early-stage bladder cancer, where it primes the immune system to fight cancer cells.

Scientists also are looking at how the vaccine works in autoimmune diseases and allergies, including multiple sclerosis, Alzheimer’s, and diabetes.

Studies suggest that live vaccines like BCG change which genes get turned on and off in different parts of the immune system, ultimately offering broader protection against a host of germs and other invaders. It also may reprogram the immune system in cases where people’s defenses overact.

Previous studies that looked at BCG and COVID failed to find any benefit from the vaccine.

A February 2022 studysuggested that BCG failed to protect against COVID-19 in mice and hamsters.

Preliminary results from a larger study released In January 2021 by researchers in the Netherlands showed that elderly patients vaccinated with BCG developed symptomatic COVID infections just as often as those who had received a placebo six months after getting the shots.

Additionally, a study published in May 2022 found that BCG did not protect health care workers in South Africa from COVID infection or severe COVID and hospitalization.

Faustman said the difference in studies is likely due to researchers using weaker strains of the vaccine. Additionally, other studies had populations where people taking the placebo might already have had some benefits from BCG — they may have been vaccinated with BCG at birth or might have previously had a TB infection (which confers a similar immunity). The placebo group in other studies might have previously had COVID or were receiving BCG with a COVID vaccine, both of which would limit their exposure to new infections.

She added that BCG takes time to confer immunity for illnesses other than TB. Because her lab was already well into a five-year clinical trial of BCG in diabetes patients, trial participants had received two of three doses of the strongest strain of the vaccine over the previous two years. Participants received the third dose in 2020.

Dr. Madhukar Pai, a prominent tuberculosis researcher with McGill International TB Centre, was skeptical of the results. He said some countries that vaccinate against TB using BCG — such as India — had some of the highest COVID death rates in the world.

Additionally, he said the study had not been set up to look at the impact on COVID from the start, and therefore wasn’t as strong as clinical trials that looked directly at whether BCG confers immune protection against COVID.

“The direct evidence I was looking for came from direct animal and human trials,” he said. “None have shown a signal, and that’s what I would tend to judge.”


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