COVID-19: Is century-old TB vaccine turning out to be a saviour for India?

A century-old vaccine against tuberculosis may well be coming in handy to help the immune system fight the COVID-19 disease. This could be the plausible reason for low mortality rate in India in the raging coronavirus pandemic.

An international team of researchers from India, China, Italy and the United States has found links between populations who had high levels of bacillus Calmette–Guérin (BCG) vaccinations, a common tuberculosis vaccine, and lower levels of COVID-19 mortality.

The link provides some definite evidence that the universal BCG vaccination may protect against COVID-19 deaths, according to a peer-reviewed study published in the journal Nature.

Countries like India which had adopted universal BCG vaccination programme have reported a remarkably low death rate compared to those who had either discontinued the vaccination or did not take it up at all.

“The differences in the death toll between countries with or without a national BCG program suggest that the vaccine has a role in lowering the COVID-19 casualty by manifold,” said Gobardhan Das, co-author of the study and a researcher from Special Centre for Molecular Medicine, Jawaharlal Nehru University (JNU).

Along with him, Abhibhav Sharma and Saurabh Kumar Sharma from JNU’s School of Computer and System Sciences, Arnab Bhattacherjee from JNU’s School of Computational and Integrative Sciences, Yufang Shi from China’s Soochow University Medical College, researchers from Italy — Gerry Melino and Ernesto Carafoli, and Enrico Bucci from Temple University, Philadelphia, USA, conducted the study.

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“We have presented the data, suggesting that the BCG immunization correlates with lower incidence and gravity of the COVID-19 disease across different countries, even when the BCG immunization was performed in childhood,” the study said.

The researchers have found that BCG vaccination rates may explain, at least partly, why death rates in countries like the United States, Italy, France, and Spain are much higher than in countries like India, Greece, Hungary, and Poland.

The findings pose a challenge to the position taken by the World Health Organisation (WHO), which said in April last that there was “no evidence” that the BCG vaccine protects against COVID-19.

What is a BCG vaccine?

The BCG vaccine was first used on humans in 1921 and became widely used around the world through the 1970s. Many countries in Europe, however, stopped routine inoculation of newborns in the 1970s amid falling levels of tuberculosis infections.

The Mycobacterium Bovis BCG strain was first developed at the Pasteur Institute. This strain was subsequently distributed to several laboratories in the world and a number of additional strains were then developed. Six major BCG strains now account for more than 90 per cent of the BCG vaccines employed worldwide. Currently, 100 million children are vaccinated globally every year.

Subsequently, BCG was shown to exhibit protective effects against leprosy and several other diseases, including those not associated with mycobacteria. Recently, BCG was shown to exhibit efficacy against type-I diabetes.

If more research adds evidence to the theory that the BCG vaccine may help protect against the most severe cases of COVID-19, the world may have to ramp up BCG vaccine production rather than diverting the existing supplies from areas vulnerable to tuberculosis outbreaks.

The production will have to increase to meet the sudden spike in vaccine demand in order to prevent a delay in distribution to countries that very much need it to fight tuberculosis.

How was the study done?

In order to investigate the impact of BCG vaccination on the spread of COVID-19, the countries were classified into three groups following the data obtained from the “BCG World Atlas” till May 29 this year.

These three groups represented 1) countries that never adopted a national BCG vaccination program, 2) countries that had a mass BCG vaccination program but discontinued it, and 3) countries with an active national BCG immunization policy.

The team collected coronavirus mortality data from around the world. From that data, it adjusted for variables, such as income, access to education and health services, population size and densities, and age distribution. Through all of the variables, a correlation held showing that countries with higher rates of BCG vaccinations had lower peak mortality rates from COVID-19.

The aim of the study was to probe the number of deaths due to COVID-19 in these three types of countries among different age groups. For this purpose, five age intervals were defined as the population below the age of 15, 15–44, 45–64, 65–79, and above 80 years.

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“Two types of comparative cross-sectional studies were performed: 1) to compare the number of respective COVID-19 cases per million in the defined age groups of three defined classes of countries based on BCG policy, and 2) to compare the number of respective COVID-19 deaths per million in the defined age groups of three defined classes of countries based on BCG policy. To obtain sufficient statistical power for data analysis, we only included countries with at least 1000 confirmed COVID-19 cases,” the researchers explained.

As the number of cases reported in lower-income countries is very low and likely due to underreporting, the researchers included only the higher-income and middle-income countries as per the World Bank classification.

Further analysis of age-related susceptibility towards COVID-19 disease has revealed that countries with universal vaccination exhibit reduced disease incidence across all age groups. Countries that discontinued vaccination appear to exhibit disease incidence at levels intermediate between vaccinated and unvaccinated countries.

“There were significant differences in mortality in all age groups between the vaccinated and unvaccinated countries, although there were no differences between the unvaccinated countries and those that have discontinued vaccination,” the study said.

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While a direct correlation between BCG vaccinations and a reduction in coronavirus mortalities still needs to be understood fully, the researchers hope that the BCG vaccine might be able to provide at least short-term protections against severe COVID-19, particularly for front-line medical workers or high-risk patients.

Meanwhile, Prof Madhukar Pai, a noted epidemiologist and director of Montreal-based McGill International TB Centre and Canada Research Chair in Epidemiology and Global Health, said it would be dangerous to make conclusions on the BCG-COVID-19 link in such a dynamic situation.

“We simply cannot act on these ecologic correlations and must wait for randomised trials on BCG and COVID-19,” he told The Federal in response to an email query.

“Several countries now have rapidly escalating COVID-19 outbreaks, including Brazil, India, Russia, Mexico, Peru and Chile. And they all routinely give BCG at birth. So, it is dangerous to make conclusions in such a dynamic situation,” Prof Pai said.eaths: Is the century-old TB vaccine turning out to be a saviour for India?