In 1921, Dr Albert Calmette, a physician and Guerin, a veterinarian discovered the first vaccine against an old foe Mycobacterium Tuberculosis. Almost a century has passed, it remains the only answer to this notorious bacterium. The BCG(Bacillus-Calmette-Guerin) vaccine is included in national immunization schedule of many countries in the world.

Click for details on BCG vaccine

It is a live attenuated vaccine that is administered intradermally preferably at birth or in the first year of life. Also, it is the only vaccine which acts by stimulating the cell mediated immunity of our body. However, this vaccine isn’t considered a very effective preventive measure for Tuberculosis and many vaccines are under trial. As of now 16 vaccines are on trial.

Since the covid-19 pandemic several drugs are being touted as the possible therapeutic option. Vaccines development takes time.Researchers and health care personals have been searching for a therapeutic option which can rescue us from this pandemic. In recent days like many other drugs BCG vaccine has been making headlines for its effectiveness.




But why BCG?

Several systematic reviews, narrative reviews, RCTs have shown that individual vaccinated with BCG vaccine have lower incidence of respiratory tract infections.

BCG also have been shown to enhance the antibody response of other vaccines as well.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single stranded positive-sense RNA virus, and the BCG vaccine has been shown to reduce the severity of infections by other viruses with that structure in controlled trials. For example, the BCG vaccine reduced Yellow fever vaccine viraemia by 71% (95% CI 6–91) in volunteers in the Netherlands,and it markedly reduced the severity of Mengovirus (encephalomyocarditis virus) infection in two studies in mice.

Various studies and researches around the world have concluded that the covid-19 related deaths were higher in countries which no longer adminster BCG in their national immunization program. Countries like USA, UK, Italy and Spain do not routinely vaccinate with BCG and these countries faced high covid-19 death rates . However, Portugal a neighbouring country of Spain where BCG is a routine vaccine had relatively fewer deaths.

Above 2 pictures help in correlating the mortality rates among countries with BCG in routine vaccination and covid-19 deaths.

However, Brazil is an outlier, which might question this theory or it may be because different countries in the world use different BCG strain in their vaccine. Brazil uses BCG brasil strain.

What is the mechanism of such cross protection?

Many theories regarding this peculiarity of BCG have been put forward and it is an active area of investigation at present.

One of the theories implies that the molecular mimicry between BCG antigens and viral antigens could lead to a population of memory B and T cells that recognize both BCG and respiratory pathogens. However, this mechanism is unlikely to explain the diverse protection resulting from BCG vaccination.

Second, BCG could lead to antigen-independent activation of bystander B and T cells, a mechanism that has been termed heterologous immunity.

Finally, BCG could lead to long-term activation and reprogramming of innate immune cells. This last mechanism, which has been the subject of much interest in the past decade, has been called trained immunity.

What are the trials studying the benefit of BCG in covid-19?

BRACE =Phase III RCT, Australia, that will recruit up to 4170 Health care workers to determine if the BCG vaccine reduces incidence and severity of COVID-19

BCG-CORONA = Phase III RCT, Netherlands, that will enroll up to 1500 HCW  to reduce absenteeism among HCW with direct patient contacts during the COVID-19

BADAS study, a phase 4 randomized trial, is conducted in the US to determine if the BCG vaccine for healthcare workers acts as a defense against COVID-19, which will enroll 1800 participants.

A study in Germany is testing whether VPM1002, a recombinant vaccine strain derived from BCG, can protect either health-care workers or older patients from COVID-19.

ICMR the Indian research body have announced the trial evaluating the efficacy of BCG vaccine in patients above 65 years against covid-19.

Many other countries have started studies for evaluating BCG efficacy.

An article in Lancet co-written by Director general of WHO, Dr Tedros A Ghebreyesus , writes “Until these trials are complete, there are four main reasons why it is very important to adhere to WHO’s recommendation that the BCG vaccine is used for COVID-19 only in randomised controlled trials.

First, the BCG vaccine is already in short supply, and indiscriminate use could jeopardise the supply needed to protect children against tuberculosis in high-risk areas.

Second, whether BCG will be effective remains unknown: findings from the ecological studies suggesting less COVID-19 in countries with routine BCG immunisation are weak evidence because they are based on population rather than individual data and are prone to confounding. Also, it is unlikely that a BCG vaccine given decades ago in childhood will ameliorate COVID-19 now. One reason for this is that the beneficial off-target effects of the BCG vaccine might be altered by subsequent administration of a different vaccine.

Third, if the BCG vaccine is not effective against COVID-19, BCG vaccination could engender a false sense of security.

Fourth, careful safety monitoring in randomised trials is needed to guard against the remote possibility that up-regulation of immunity by BCG will exacerbate COVID-19 in a minority of patients with severe disease.”

Covid-19 pandemic has become one of the worst nightmares of the human civilisation. Till we find something that can really work wonders the best we can do now is take precaution. Maintaining social distancing, taking care of our personal hygiene and  leading a healthy lifestyle is the only option right now.


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