The 144 diabetes study participants were enrolled in the parallel trial, which ran from January 2020 to April 2021, before any 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 prior infection during the 15-month study. Of those treated with placebo, six tested positive for COVID antibodies.
Andrew DiNardo, assistant professor of infectious diseases 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 into whether BCG can protect healthcare workers from the virus.
Although the nation has specific COVID vaccines readily available, DiNardo said those vaccines have not been as durable or as protective against the breakthrough infections as scientists had initially hoped. The MGH study raises the possibility that BCG could be used alongside COVID vaccines to boost immunity, he said.
“You might not need a boost that often,” he said. “I think it will be interesting now to see if there are additional clinical trials on how the specific COVID vaccine works alongside the BCG vaccines.”
Denise Faustman, an 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. 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. An earlier small 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 protect against tuberculosis, with 100 million doses of the vaccine given to newborns in 84 percent of the world’s countries. Because tuberculosis is uncommon in the United States, children here have never received the vaccine.
The shots are controversial. They do not fully protect against tuberculosis in adults. However, researchers have shown that the vaccine is protective against other related and unrelated diseases, such as leprosy and early-stage bladder cancer, where it primes the immune system to fight cancer cells.
Scientists are also studying how the vaccine works in autoimmune diseases and allergies, such as multiple sclerosis, Alzheimer’s and diabetes.
Studies suggest that live vaccines like BCG change which genes are turned on and off in different parts of the immune system, ultimately offering broader protection against a host of germs and other invaders. It can also reprogram the immune system in cases where people’s defenses are overactive.
Previous studies looking at BCG and COVID found no benefit from the vaccine.
A February 2022 study published in Cell Reports suggested that BCG did not protect against COVID-19 in mice and hamsters.
Preliminary results of a larger study published in January 2021 by researchers in the Netherlands showed that elderly patients vaccinated with BCG developed symptomatic COVID infections as often as those who received a placebo six months after receiving the vaccinations.
Additionally, a study published in eClinicalMedicine in May 2022 found that BCG did not protect healthcare workers in South Africa from COVID infection or severe COVID-19 and hospitalization.
Faustman said the difference in the studies is likely due to researchers using weaker strains of the vaccine. Also, other studies had populations where people taking the placebo may already have had some benefit from BCG: they may have been vaccinated with BCG at birth or may have previously had a TB infection (which confers similar immunity). The placebo group in other studies may have previously had COVID or were receiving BCG with a COVID vaccine, which would limit their exposure to new infections.
He added that BCG takes time to confer immunity for diseases other than tuberculosis. Because his lab was already in a five-year clinical trial of BCG in patients with diabetes, the trial participants had received two of three doses of the strongest strain of the vaccine in the previous two years. Participants received the third dose in 2020.
Dr. Madhukar Pai, a leading tuberculosis researcher at the McGill International TB Centre, is 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.
He also said the study was not designed to look at the impact on COVID from the outset, and therefore was not as strong as clinical trials looking 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 any signs, and that’s what I tend to judge.”