Ninety years ago, following Robert Koch discovery of Mycobacterium tuberculosis, scientists across the world set out to invent a vaccine to fight the disease. In 1908, bacteriologist Leon Calmette and veterinarian Camille Guerin, who worked at the Pasteur Institute in France, began an experiment to devise a vaccine by attenuating a Mycobacterium bovis strain until it lost its virulence.
Thirteen years and 230 trials later, an infant was given the first dose of this live attenuated vaccine, Bacille Calmette-Guerin (BCG). Now, with over three billion doses already administered, BCG is the most widely used vaccine worldwide against Pulmonary TB.
As scientists around the world are burning the midnight oil to find new drugs and antidotes for the COVID-19 virus, a vaccine that is more than a century old has piqued researchers’ interests. The BCG vaccine is currently being studied in clinical trials around the world as a way to fight COVID-19.
Tuberculosis and COVID-19 are very different diseases. For starters, TB is caused by a type of bacteria while COVID-19 is caused by a virus, But the BCG vaccine might help people build immune responses to things other than TB, causing ‘off-target effects,’ reducing viral illnesses, respiratory infections and sepsis, and could bolster the body’s immune system.
The BCG vaccine’s immune boosting effects against severe respiratory infections caught researchers’ interest in 2011 when a study from West Africa claimed that infectious disease mortality rates in low-birth-weight babies who were vaccinated were cut by more than 40 percent.
A larger sample of over 150,000 children across 33 countries was observed in an epidemiological study and it reported a 40 percent lower risk of acute lower respiratory tract infections in children who received the BCG vaccine.
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BCG vaccine is the answer?
A new scientific study has discovered a possible correlation between countries where it is mandatory to be vaccinated against TB with BCG, and the impact of the new coronavirus.
“We found that countries without universal policies of BCG vaccination (Italy, Netherlands, USA) have been more severely affected compared to countries with universal and longstanding BCG policies,” the authors of the study wrote.
We all are looking for answers to how to combat the COVID-19 disease, but the results of this study are too soon to tell and too early to conclude. One of the main limitations of the study is that it compares data from different countries, which have different timelines for COVID-19 and different abilities to test. The countries that have been taken as standard — where the BCG vaccine is compulsorily provided as a part of national immunisation programme, such as India — are grossly undertesting for COVID-19. This implies that the number of cases are seriously under-reported, since COVID-19 symptoms overlap with many other respiratory infections and fevers.
The demographic distribution may be a factor too. According to recent population data, while the US, UK and Italy have an ageing population that are susceptible to the coronavirus infection, countries like India have a relatively younger population. This factor has not been taken into consideration while undertaking the study.
The coronavirus itself is not what kills people. What kills people with the infection is an excessive, overly robust inflammatory response by the immune system that creates a cytokine storm. A cytokine is a large group of proteins, peptides or glycoproteins that are secreted by specific cells of the immune system. A cytokine storm is an overreaction of the body’s immune system. A COVID-19 patient dies because their immune systems respond too robustly to the virus, in an overly inflammatory way.
The very reason that the BCG vaccine helps infants has the potential to push the immune system to respond non-specifically and excessively. This could be detrimental and cause people to have more severe illness from the virus. Recent reports from China that low-level TB infections are associated with severe COVID-19 cases is concerning, because the BCG vaccine is a live attenuated bacterium that is closely related to the TB bacteria and could have a similar effect on exacerbating severe COVID-19 infections.
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Wait and see
Randomised trials are the only answer. The initial euphoria around the BCG vaccine as an antidote to COVID-19 is quite like the one around hydroxychloroquine. We hope that both pass the test, but until then, testing, contact tracing and social distancing are our only answers. We need to take a break from ‘real-time updates’ on the COVID-19 vaccine trials. We can’t afford to hoard the BCG vaccines for potential COVID-19 use — as it happened with hydroxychloroquine — since the BCG supply chain is weak, and it is crucial to protect children from childhood TB, the risk of which is very high in developing countries.
On 12 April, the WHO updated its ongoing evidence review of the clinical trial repositories and in a scientific brief said: “The review yielded three preprints (manuscripts posted online before peer-review), in which the authors compared the incidence of COVID-19 cases in countries where the BCG vaccine is used with countries where it is not used and observed that countries that routinely used the vaccine in neonates had less reported cases of COVID-19 to date. Such ecological studies are prone to significant bias from many confounders, including differences in national demographics and disease burden, testing rates for COVID-19 virus infections, and the stage of the pandemic in each country.”
Immunising against the COVID-19 disease by using the 100-year-old BCG vaccine would thus seem to have much in common with life itself, as surmised by Soren Kierkegaard, “Life can only be understood backwards, but it must be lived forwards.”
Dr Pooja Tripathi is a public health professional. She has previously worked with Gates Foundation & World Bank’s Global HIV/AIDS Program. Views are personal.
The article was first published on the Observer Research Foundation website.