BCG vaccine protects people with type 1 diabetes from severe COVID-19

A new study led by researchers at Massachusetts General Hospital (MGH) shows that the century-old BCG (Bacillus Calmette-Guerin) vaccine, originally developed to prevent tuberculosis, protects people with type 1 diabetes from severe illness from COVID-19 and others. Infectious diseases.

Two randomized, double-blind, placebo-controlled studies showed that the BCG vaccine provided continued protection throughout most of the COVID-19 pandemic in the United States, regardless of viral variant.

"People with type 1 diabetes are highly susceptible to infectious diseases and have worse outcomes when infected with the SARS-CoV-2 virus," said senior study author Dr. Denise Faustman, director of the Laboratory of Immunobiology at MGH and assistant professor of medicine at Harvard Medical School.

"Published data from other researchers show that mRNA COVID-19 vaccines are not very effective in this group of vulnerable patients. But we have shown that BCG can protect type 1 diabetics from COVID-19 and other infectious diseases." p>

The 18-month phase III study, published in iScience was conducted late in the pandemic in the US, when the highly contagious omicron variant was circulating. The 15-month phase II study was conducted early in the pandemic; the results of this study were published in Cell Reports Medicine.

During the COVID-19 pandemic, several international studies have tested whether BCG, as a single dose or booster given to previously vaccinated adults, can protect them from infection and COVID-19. These studies add to a large global clinical trial database showing that BCG administered to newborns works as a platform for all infectious diseases, possibly for decades. But the results of these studies of BCG boosters in previously vaccinated people were mixed: five randomized trials showed effectiveness and seven did not.

The phase II and III MGH clinical studies testing BCG differed from other BCG studies in important respects. Instead of receiving one dose of BCG, participants received five or six doses of a particularly powerful strain of BCG vaccine. US participants were followed for 36 months instead of weeks or months.

"We know that in people who have not previously received the BCG vaccine, off-target effects may take at least two years to achieve full protection," Faustman said. "Giving the vaccine multiple times may speed up this process."

Importantly, the US population has never received the BCG vaccine, so these clinical studies were not booster studies.

“The Phase II and III trials conducted at MGH were unique because they were the only COVID-19 trials in the world in which the population did not receive the BCG vaccine and was not exposed to tuberculosis,” Faustman said. "Trials conducted in countries where participants had previously received BCG vaccine as infants or had been exposed to tuberculosis may have masked any benefit from the BCG booster."

The MGH studies included 141 people with type 1 diabetes; 93 people in the treatment group received five or six doses of the BCG vaccine, and 48 people in the placebo group received the dummy vaccine and were followed for 36 months to track different genetic variants of COVID-19 and many infectious diseases.

During an early phase II study (January 2020 to April 2021), when the virus was more deadly but less contagious, the BCG vaccine was 92% effective, comparable to the effectiveness of the Pfizer and Moderna vaccines against COVID-19 in healthy adults.

During all 34 months of the COVID-19 pandemic in the United States, the BCG vaccine had a significant effectiveness of 54.3%. The researchers also found that participants who received BCG treatment had lower rates of viral, bacterial and fungal infections, as well as COVID-19 disease itself.

The BCG vaccine provides immunity that is likely to last for decades, a clear advantage over the COVID-19 vaccine and vaccines against other infectious diseases such as influenza, where the duration of effectiveness is only two or three months. p>

“The BCG vaccine offers the prospect of nearly lifelong protection against all variants of COVID-19, influenza, respiratory syncytial virus and other infectious diseases,” Faustman said.

Some of the participants who received BCG treatment also received commercially available COVID-19 vaccines during the phase III trial. The researchers noted that the Pfizer, Moderna and Johnson & Johnson did not protect people with type 1 diabetes from COVID-19.

"Our study showed that the BCG vaccine did not increase the effectiveness of the COVID-19 vaccine, and was not harmful to those who received the COVID-19 vaccine," Faustman said. "As the pandemic continues to evolve, it will be interesting to see if we can work with the FDA to provide access to the BCG vaccine for type 1 diabetics, who appear to be particularly at risk for all infectious diseases."