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Examining the Long-Term Protective Effects of Childhood Vaccination

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Being vaccinated during childhood with the BCG (Bacille Calmette-Guérin) vaccine against tuberculosis is not a long-term protective factor against COVID-19, despite what was thought at the beginning of the pandemic. Professor Marie-Claude Rousseau, a researcher in epidemiology at the Institut national de la recherche scientifique (INRS), along with researchers from the Université de Sherbrooke,  Université de Montréal, and Université Laval, has conducted the first-ever study in Quebec comparing childhood vaccination status in people with COVID-19 and a control group. Professor Marie-Élise Parent and research officer Jennifer Yu, both from INRS, were also part of the team.

The research, published in the Vaccine journal, brings new light on the possible link between the BCG vaccine and COVID-19.

An important public health message

Most published studies to date have shown a correlation between BCG vaccination in the population and a lower mortality rate from COVID-19. However, according to the team of Quebec scientists, the methodology of these studies did not determine whether those who received the BCG vaccine were also the ones with better survival, nor did it take into account certain factors that could have biased the analyses.  

“Even if our results turned out to be negative, it is important to communicate them to the public, since they contrast with those obtained in previous studies, which had important methodological weaknesses. Our results are therefore the most valid ones available on this subject to date.”  

The researcher recalls that a potential protective effect of the BCG vaccine against COVID-19 was the subject of a great deal of scientific and media interest very early in the pandemic. 

“In the past year, we have had 25 times more requests from the public to verify whether they had received the BCG vaccine as a child,” says professor Rousseau who is also the scientific manager of the Quebec BCG vaccination registry hosted by INRS, a unique computerized resource that lists 4.2 million vaccination certificates issued in the province between 1956 and 1992.

“Our study has shown convincingly that BCG, a strong stimulator of innate immunity, does not confer very long-term protection against COVID-19. This is not the result we were hoping for, but at least this matter, especially relevant for countries in the South, can be taken off the table,” says Dr. Jacques Pépin, first author of the study and associate professor at the Université de Sherbrooke and the CHUS Research Centre.

No long-term protection 

The research team recruited 920 individuals who tested positive on a PCR test for COVID-19 at Hôpital Maisonneuve-Rosemont (HMR) from the CIUSSS de l’Est-de-l’Île-de-Montréal, and the Centre hospitalier universitaire de Sherbrooke (CHUS) between March and October 2020. In parallel, the control group consisted of 2,123 people who did not have COVID-19, but had another sample analyzed at the microbiology laboratories during the same period. 

Only individuals born in Quebec between 1956 and 1976 were recruited. Their vaccination status was verified in the Quebec BCG vaccination registry using the information they provided to the research team. Among those who tested positive for COVID-19, 54% had received the BCG vaccine during childhood. This proportion was 53% in the control group.

The researchers found no long-term protective effect of BCG. Their analyses controlled for other factors such as the type of job the person had, biological sex, age, an index of material deprivation, and whether they lived in a rural or urban area. 

“Although we expected to observe a small protective effect, we were not surprised by the results. After all, participants had received the vaccine decades ago. Among those who had received the vaccine more recently, in the early 1970s, no protective effect was also observed. However, the number of people was limited, greatly reducing the possibility of detecting a small effect,” explains Professor Rousseau. 

A vaccine of great interest   

Professor Rousseau notes that some studies have suggested a short-term protective effect of BCG against COVID-19 and that clinical trials are underway internationally, which seems promising.

“It’s interesting to see the renewed interest in this century-old vaccine, particularly with respect to its effects that are unrelated to tuberculosis, in the last five to ten years.”

Professor Rousseau has been awarded a project grant of nearly $400,000 from the Canadian Institutes of Health Research (CIHR) allowing her, among other things, to test these results on a larger cohort of 400,000 people among the last generations to have received the BCG vaccine.

The main objective of this new project is to examine the overall non-specific effects of BCG vaccination over the long term and to see if people who have been vaccinated with BCG have a better survivability.

The researcher will also look at whether the vaccine provides a protective effect against other infectious agents such as pneumococcus, group A streptococcus and meningococcus.

Reference: Pépin J, Labbé A-C, Carignan A, et al. Does BCG provide long-term protection against SARS-CoV-2 infection? A case–control study in Quebec, Canada. Vaccine. 2021. doi: 10.1016/j.vaccine.2021.08.019

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