MONTREAL -- Childhood vaccination against tuberculosis does not appear to provide long-term protection against COVID-19, according to work by Quebec researchers.

Several studies conducted since the beginning of the pandemic suggested that the BCG (Bacille Calmette-Guérin) vaccine against tuberculosis could offer some protection against SARS-CoV-2, the virus that causes COVID-19.

Researchers from the Institut national de la recherche scientifique (INRS), Université de Sherbrooke, Université de Montréal and Université Laval conducted the first-ever study in the Quebec population comparing childhood vaccination status in individuals with COVID-19 and a control group.

"We showed that there was no protective effect of having received the BCG vaccine during childhood compared to the risks of COVID-19 today," wrote Marie-Claude Rousseau, a professor and epidemiologist at INRS who is the lead author of the new study published by the medical journal Vaccine.

Most studies published to date have shown a correlation between BCG vaccination in the population and a lower rate of mortality from COVID-19.

However, according to the Quebec researchers, the design of these studies did not allow for the determination of whether those who received the BCG vaccine had better survival, nor did it allow for the consideration of certain factors that might have biased the analyses.

"The difficulty with the earlier studies is that there was no individual information known," said Rousseau. "The correlations that were observed were at the population level, but we didn't know whether it was actually people who had received the BCG vaccine who had lower mortality or who had a lower risk of contracting COVID-19."

NO PROTECTIVE EFFECT

The cohort consisted of 920 individuals born in Quebec between 1956 and 1976 who tested positive for COVID-19 by PCR screening at Hôpital Maisonneuve-Rosemont and Centre Hospitalier Universitaire de Sherbrooke between March and October 2020. The control group consisted of 2,123 individuals who tested negative for COVID-19.

The subjects' vaccination status was verified in the Quebec BCG vaccination registry using the information they provided. Fifty-four per cent of the participants who tested positive for COVID-19 had received the BCG vaccine during childhood, compared with 53% in the control group.

Thus, the scientists could not observe any long-term protective effect of BCG. Their analyses controlled for other factors such as the type of job the person had, biological sex, age, index of material deprivation, and whether they lived in a rural or urban area.

However, Rousseau said their results only address the protection that would be enjoyed today by individuals who were vaccinated 40 or 50 years ago.

"We can't rule out the possibility that there may be protection in the shorter term," she said. There are some studies, which are not randomized clinical trials ... that suggest some short-term protective effect."

Clinical trials are reportedly underway in more than 15 countries to determine whether BCG may offer short-term protection against infection or severity of COVID-19.

Researchers at the University Health Network in Toronto announced a new study of BCG earlier this month. They hope to recruit 3,600 early respondents to see if the vaccine can reduce the incidence and severity of COVID-19 infection. They will use an improved version of the vaccine, hoping to elicit a more robust immune response.

Based on a new analysis of data compiled by the Johns Hopkins University Coronavirus Resource Center, a letter published in late September by the Proceedings of the National Academy of Sciences pointed out that deaths from the pandemic have skyrocketed this summer in Bolivia, Panama, Colombia, Peru, Brazil, Mexico, and South Africa, even though their populations are heavily protected by BCG.

TRAINED IMMUNITY

The BCG vaccine has been around for decades. Over time, scientists have found that it appears to generate protection beyond tuberculosis alone.

This is the phenomenon of "trained immunity," which was discovered a few years ago. The immune cells that represent the body's first line of defence seem to undergo changes that make them more effective when they encounter an infectious agent, even if it is not the TB agent.

Studies in developing countries, for example, have found a lower mortality rate in children who were vaccinated with BCG.

Two World Health Organization reports in recent years have concluded that BCG has a protective effect, especially since mortality in developing countries is primarily related to infectious diseases.

A study published last month by the medical journal Cell also showed a reduced incidence of severe respiratory viral infections among Greek seniors who received BCG.

Professor Rousseau's future work will focus on the non-specific effects of the BCG vaccine, which she has been studying for the past 15 years.

Routine vaccination against tuberculosis in Canada and Quebec ceased in the mid-1970s.

-- This report by The Canadian Press was first published in French on Oct. 25, 2021.