Like it or not we are in the midst of a pandemic and I can’t shy away from writing or reading about it. The deadly corona virus has spread to over 213 countries and has caused over 2.7 million infections with over 373,000 deaths and counting. The global race is on to find the magic drug to treat the disease and/or a vaccine to eradicate it.

While pondering about the pandemic, one staggering statistic caught my attention. India with a population of over 1.38 billion, has 180,000 confirmed cases of the corona virus with over 5000 deaths till date. This statistic, if accurate, is quite fascinating given the density of the Indian population, with majority of the people living below the poverty line with poor healthcare system and often unhygienic sanitary conditions. While developed countries like the UK and the US are struggling to control the devastation caused by the COVID-19, the low death toll due to the virus in India, begs the question is it true? And if yes, why? and how?

In a country where new viruses like Dengue, Chikunguyna and the likes surface every year and affects millions, it could potentially seem logical that the innate immune system of the Indian population is better adapted to fight a virus like COVID-19. Another plausible explanation is that most of the population in India have been vaccinated against tuberculosis (TB) with the Bacillus Calmette–Guérin vaccine. Yep I have been vaccinated too with a characteristic scar on the arm.

There is tantalizing evidence suggesting that being vaccinated against TB with BCG could lead to better prognosis against COVID-19. Is there any truth to this? Lets investigate.

A modelled mortality and morbidity study in two dozen countries reported that those countries without universal BCG vaccination, such as Italy, the US, and the Netherlands, were more severely affected by the pandemic than those with universal vaccination.  Although this study is not peer reviewed and is based mainly on statistics and not on cause and effect, we still have can’t turn a blind eye to the positives if any of the BCG vaccine.

What is BCG?

Bacillus Calmette–Guérin (BCG) vaccine is a century old vaccine primarily used against tuberculosis. The vaccine was invented by two French bacteriologists Albert Calmette and Camille Guérin, who named the product Bacillus Calmette-Guérin, or BCG. The BCG vaccine consists of a live weakened strain of Mycobacterium bovis, a cousin of M. tuberculosis, the bacterium that causes TB.

BCG has been given to more than 4 billion individuals, making it the most widely administered vaccine globally. In countries where TB is prevalent, one dose is recommended in healthy babies as close to the time of birth as possible. In areas where TB is not prevalent, only children at high risk are typically immunized, and suspected infected individuals are tested for and treated.

How does BCG affect COVID-19?

The BCG vaccine has a specific effect against TB. Unlike most known drugs or treatment options, BCG seems to also have beneficial nonspecific (off-target) effects on the immune system that protect against a wide range of other infections. In fact BCG is used routinely to treat bladder cancer. Randomised controlled trials have provided evidence that the BCG vaccine’s immunomodulatory properties can protect against respiratory infections.

The BCG vaccine and some other live vaccines are purported to induce metabolic and epigenetic changes which leads to augmentation of the innate immune response to subsequent infections, a process called trained immunity. Hypothetically, BCG vaccine might be able reduce viraemia (the presence of viruses in the blood) after SARS-COV-2 exposure, with consequent less severe COVID-19 and more rapid recovery.

Randomised controlled trials are underway in the Netherlands and Australia to assess whether BCG reduces the incidence and severity of COVID-19 in health-care workers, and the effect this has on time away from work (NCT04327206, NCT04328441).

While time will only tell if the results from these clinical trials seem to prove the theory that BCG protects/ reduces the severity of COVID-19, we need to adhere to the WHO guidelines. WHO’s recommendation is that the BCG vaccine is used for COVID-19 only in randomised controlled trials at this time. Among other reasons a) if it turns out that the BCG vaccine is not effective against COVID-19, BCG vaccination could leave individuals with a false sense of security, b) results from these clinical trials is very vital before we head off to vaccinate ourselves with BCG (if not already), mainly due to the remote possibility that the enhancement of immunity by BCG could exacerbate COVID-19 in a minority of patients with severe disease.

Take Home: Statistics from India seems to provide favourable support to the fact that the BCG vaccine might be beneficial to the population to decrease the severity of the COVID-19. Randomised controlled Phase 3 and Phase 4 clinical trials are underway to investigate if BCG has a positive effect on the severity of the disease. BCG seems to show some promise. Time will tell.