The inexpensive and widely-used Bacillus Calmette–Guerin (BCG) vaccine that protects against childhood tuberculosis also prevents severe infection and death from coronavirus disease (Covid-19), concluded two peer-reviewed studies released last week, including one led by Indian researchers from the Jawaharlal Nehru University (JNU) Delhi.

The JNU study from India found that the quality of protection depends on the BCG strain used to make the vaccine, with Mixed, Pasteur and Japan strains being superior to the three other strains which together account for more than 90% of the BCG vaccines being used in the world. The peer-reviewed study was published in Cell Death and Disease, which part of the Nature group of journals. The second study from the US, published in the Proceedings of the National Academy of Sciences, also linked BCG vaccination with reduced Covid-19 deaths.

“Those who got BCG vaccination, not just in India but in other countries, are more protected than those who were not, shows this analysis of data for countries with over 1,000 reported cases. We think BCG-mediated immune response would help in lowering both incidence and severity of infection,” said study author Gobardhan Das, chairperson, Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi. Around 100 million children around the world get the BCG vaccine every year.

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The six major BCG strains that now account for at least 90% of the BCG vaccines employed worldwide are Pasteur, Danish, Glaxo 1077 (derived from the Danish strain), Tokyo, Russia, and Moreau. “The data shows that BCG offers some degree of protection against Covid-19, but all the countries (that give BCG vaccines to their children) do not do equally well, so we looked at which strain offered better protection. We analysed all the strains being used and found that some of the strains, such as BCG Mix, BCG Pastuer, and BCG Tokyo do better compared to others, such as BCG Russia and BCG Danish. India uses BCG Mix vaccine,” said Das.

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BCG vaccination of children began in India in 1949; in 2019, at least 97% of the 26 million Indian children born that years received it. The vaccine protects against disseminated TB and meningitis in childhood, but doesn’t offer protection from adult pulmonary TB, which has led to several countries discontinuing its use.

“BCG is a potent immune-modulator, especially of the cell-mediated immunity. BCG has protective effects against leprosy, buruli ulcer, bladder cancer, type-1 diabetes and several other diseases, including those not associated with mycobacteria. Macaques immunised with BCG have incidence of pulmonary infections, which led to a proposal for BCG immunisation for the prevention against various respiratory infections. Since Covid-19 is also a respiratory infection, it gives another basis for the study,” said Das, who did the study with researchers from the JNU School of Computer and System Sciences, and School of Computational and Integrative Sciences.

Many clinicians and epidemiologists are unconvinced about the findings. “I don’t think there’s convincing evidence, which we can only get from randomised controlled trials that enroll a large number of people. It is highly unlikely that the protection will last till adulthood, we have convincing evidence from India that it does not protect against adult TB, even in children, it just prevents simple TB from becoming systemic and affecting the brain and other organ,” paediatric pulmonologist Dr Krishnan Chhugh, director of paediatrics at Fortis Memorial Research Institute, Gurugram.

Epidemiologists are concerned that most countries with high BCG vaccination rates are not testing enough and those that are registering a sharp increase in numbers. “Several countries now have rapidly escalating Covid-19 outbreaks, including Brazil, India, Russia, Mexico, Peru, Chile. And they all routinely give BCG at birth. So, it is dangerous to make conclusions in such a dynamic situation. We simply cannot act on these correlations and must wait for randomised trials on BCG and Covid-19,” tweeted Prof Madhukar Pai, director, McGill Global Health Programmes, McGill University, Montreal, Canada.

“We can’t say `We have been vaccinated, we are safe’. If it works to some extent, it will be great, but even then, it will not be a game changer,” said Dr Chugh.