How a century-old tuberculosis vaccine may help fight severe COVID-19

In the search for weapons against COVID-19, scientists have been repurposing existing drugs as a rapid way to lower the chances of hospitalization and death. Now, a research group in India has found that a century-old tuberculosis vaccine may have potential for fighting the disease.

The Bacillus Calmette-Guérin (BCG) vaccine, which has been widely used to fight tuberculosis, has a broad effect on reducing the blood levels of inflammatory molecules in elderly people, scientists at the Indian Council of Medical Research’s (ICMR’s) National Institute for Research in Tuberculosis reported in a new study published in Science Advances.

Because uncontrolled inflammation is a key factor in severe COVID-19, the finding suggests that the BCG vaccine could be administered to high-risk adults who are unable to access vaccines as a way to fend off dangerous inflammatory responses should they contract the virus, the researchers said.

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BCG, first used in humans in 1921, is a live-attenuated vaccine. While it’s mainly used to fight tuberculosis, the shot is thought to confer broad protection against other respiratory diseases by preparing the body with a strong, nonspecific innate immune response.

But the possibility that BCG could induce a highly proinflammatory response raised concern that it might worsen infection in otherwise mild COVID cases. So, the ICMR team set out to examine the effect of BCG in the context of COVID.

The researchers vaccinated 82 people aged between 60 and 80 with BCG and compared their blood samples one month after vaccination.

Surprisingly, the study participants showed a significant decrease in blood levels of several proinflammatory cytokines, including TNF-alpha, interleukin-2 (IL-2), IL-6, GM-CSF, type 1 interferons, among others. The levels were also lower compared with those from a group of unvaccinated individuals.

What’s more, the BCG vaccination also led to reduced levels of chemokines, acute phase proteins and matrix metalloproteinases, which are associated with inflammation, the team found.

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BCG’s ability to change certain aspects of the immune system has attracted interest from other research groups targeting different diseases. Scientists at Massachusetts General Hospital found that BCG could correct regulatory T cells, or Tregs, which rein in an immune response to prevent the autoimmune destruction of insulin-producing pancreatic cells. The team recently reported positive phase 2 results showing the vaccine may help patients with Type 1 diabetes.

Many of the proinflammatory cytokines that BCG dampened in the COVID study are known to drive COVID-19 disease severity. So the ICMR researchers suggested that BCG could be used to prevent severe COVID by dialing down damaging inflammatory responses.

“We think BCG could be administered as a bridge vaccine when COVID vaccines are in short supply or as an adjunct to COVID vaccines in order to protect against morbidity and mortality in the elderly,” Subash Babu, corresponding author of the study, said in a statement.

In an accompanying editorial, Valerie Koeken at the Radboud University Medical Center noted that it will be important to determine how durable the decrease in inflammatory proteins is in patients receiving BCG. And a more extensive clinical trial would be required to determine whether the decrease is of any clinical significance in reducing severe COVID or other immune-related diseases.