Amid the debate over the protection offered by BCG vaccination—or revaccination in the case or countries such as India where it is given after birth—against COVID-19, the Indian government is planning trials with BCG vaccine.
“The ICMR is planning a study on BCG revaccination, and it is likely to start in a week,” said Dr Raman R. Gangakhedkar, head, epidemiology and communicable diseases, at the daily press briefing on Friday.
Weighing in on the issue, Gangakhedkar said there isn’t enough evidence to take an official position on the subject of BCG. “But I will try to offer an explanation on personal level,” he added.
The vaccine, he said, couldn’t even protect people against TB. “It only offers partial protection against severe TB or TB meningitis. Some studies, though, have found that it works as an immunomodulator in cancer, helping natural killer cells to work against cancer cells. But will we see this effect on it in this case (COVID-19) also? I think it is unlikely,” he said, sounding a note of caution. “This is because the effect only lasts until 15 years. Some studies suggest that revaccination should be done in adolescents; but for those above 15 years, there is not enough evidence to suggest that it will work in protecting against COVID-19,” he added.
On April 12, the WHO also said enough evidence was not available on the subject. “There is no evidence that the Bacille Calmette-Guérin (BCG) vaccine protects people against infection with COVID-19 virus. Two clinical trials addressing this question are underway, and WHO will evaluate the evidence when it is available. In the absence of evidence, WHO does not recommend BCG vaccination for the prevention of COVID-19. WHO continues to recommend neonatal BCG vaccination in countries or settings with a high incidence of tuberculosis,” the organisation said in a statement.
There is experimental evidence from both animal and human studies that the BCG vaccine has “non-specific” effects on the immune system. “These effects have not been well characterised and their clinical relevance is unknown,” it said.
According to a review by the WHO, there are three preprints (manuscripts posted online before peer-review), in which the authors have 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.”
The review also yielded two registered protocols for clinical trials, both of which aim to study the effects of BCG vaccination given to health care workers directly involved in the care of patients with COVID-19.
“BCG vaccination prevents severe forms of tuberculosis in children and diversion of local supplies may result in neonates not being vaccinated, resulting in an increase of disease and deaths from tuberculosis. In the absence of evidence, WHO does not recommend BCG vaccination for the prevention of COVID-19. WHO continues to recommend neonatal BCG vaccination in countries or settings with a high incidence of tuberculosis,” it added.
In a detailed of the ecological study, PhD students in epidemiology at the McGill International TB Centre, Montreal, Canada, wrote that since the study was done, the pandemic has escalated in many countries, including low and middle income countries (LMICs) where BCG is given at birth. “For example, COVID-19 cases in India have increased from 195 on March 21 to 1,071 on March 31. In South Africa, cases have increased from 205 on March 21 to 1,326 on March 31. Therefore, the paper’s findings could look very different as countries progress in their epidemic timelines (and expand diagnostic capacity).” The critique also pointed out that testing rates in countries were low.
The authors also said a critical flaw in the methodology of the study is the fact that a perceived relationship between an exposure and an outcome does not mean one causes the other. “Specifically, in the case of the relationship between universal BCG vaccination and the apparent lower COVID-19 case numbers and COVID-19-associated deaths, a multitude of underlying factors are at play. The crucial takeaway here is that if these factors could be appropriately accounted for, we would very likely not see the association between BCG vaccination and protection against COVID-19 as suggested by this paper,” they said.