BCG Vaccination May Help Protect Older Adults From COVID-19

By Marilynn Larkin

August 20, 2021

NEW YORK (Reuters Health) - Bacillus Calmette-Guerin (BCG) vaccination could be useful against COVID-19 in older adults in India, a study of inflammatory biomarkers before and after BCG vaccination suggests.

"We examined whether administering BCG, which is a live attenuated vaccine, to elderly individuals living in COVID-19 hotspots in India would lead to enhanced systemic inflammatory responses," Dr. Subash Babu of the ICMR-National Institute for Research in Tuberculosis in Chennai, India told Reuters Health by email. "Such a response could have potentially detrimental effects on the host response to COVID-19, as exaggerated cytokine, chemokine and acute-phase responses are harmful in the setting of acute COVID-19."

"The findings were a surprise and of major novelty and interest," he said, "since dampening or ameliorating inflammatory responses by a single dose of BCG vaccine could potentially have many benefits in many conditions, including infectious diseases, autoimmune disease and other inflammatory pathologies."

"We need to wait for efficacy studies to be completed (ours is not the only clinical trial on BCG against COVID) and then utilize the data to take a call on using BCG as an adjunct or host-directed vaccine for COVID," he added.

As reported in Science Advances, the team investigated effects of BCG vaccination on unstimulated plasma levels of a wide panel of cytokines, chemokines, acute-phase proteins (APPs), matrix metalloproteinases (MMPs), and growth factors in healthy older adults living in COVID-19 hot spots between June 2020-October 2020.

Eighty-two participants (61%) received a single dose of BCG vaccine, and 55 unvaccinated individuals served as controls. Overall, the median age was 66 and about 61% were men.

Plasma levels of proinflammatory biomarkers were measured at baseline (before vaccination) and 1 month after vaccination.

Vaccination resulted in diminished plasma levels of types 1, 2, and 17 and other proinflammatory cytokines, and type 1 interferons. It also led to decreased plasma levels of CC, CXC chemokines, APPs, MMPs, and growth factors.

Further, plasma levels of these proinflammatory markers were significantly lower in vaccinated compared to control individuals.

The authors conclude, "Our study demonstrates the immunomodulatory properties of BCG vaccination and suggests its potential utility in nonspecific vaccination of COVID-19 by down-modulating pathogenic inflammatory responses."

Dr. Valerie Koeken of Radboud University Medical Center in Nijmegen, Netherlands, author of a related editorial, commented in an email to Reuters Health, "From previous studies, we have learnt that the BCG vaccine provides protection against unrelated infectious diseases. For this reason, BCG is currently being studied in multiple randomized-controlled trials all around the world, to test if it is also able to provide protection against COVID-19."

"In addition to effects on the innate immune system, we have recently observed that BCG leads to a reduction in circulating inflammatory markers 2 weeks as well as 3 months after vaccination," she said. "While this study cohort mainly consisted of young adults, (the current study) now reports that BCG also leads to a reduction in inflammatory markers in the elderly one month after vaccination."

"Together with previous studies," she said, "they reveal that BCG induces an interesting combination of non-specific effects: it enhances the innate immune response upon infection, while also reducing the concentration of inflammatory markers in the circulation."

"Especially for the elderly, this could be very relevant in the context of inflammaging," she noted. "Inflammaging is a chronic, low-grade systemic inflammation that develops with age, and is linked to inflammation-related diseases such as cardiovascular disease, cancer and diabetes. As BCG is able to reduce the level of circulating inflammatory markers, it might be possible to use it in the future to prevent or revert inflammaging."

"At this moment, however, there are still a number of knowledge gaps we need to fill before we can think about deploying BCG in this manner," she said. "First of all, we still don't understand how BCG is able to cause this reduction in inflammatory markers. Secondly, we need to know how long these effects on systemic inflammation persist - is it only for a few months, or maybe for a year or longer? And finally, this reduction in inflammatory markers has as of yet not been linked to any clinical endpoints."

"We first need to study if these effects on circulating inflammatory proteins are of any clinical relevance, and if they prevent or reduce the impact of inflammation-related or infectious diseases," Dr. Koeken concluded.

SOURCE: Science Advances, online August 4, 2021