Does BCG provide long-term protection against SARS-CoV-2 infection? A case-control study in Quebec, Canada

Jacques Pépin; Annie-Claude Labbé; Alex Carignan; Marie-Elise Parent; Jennifer Yu; Cynthia Grenier; Stéphanie Beauchemin; Philippe De Wals; Louis Valiquette; Marie-Claude Rousseau

doi:10.1016/j.vaccine.2021.08.019

Does BCG provide long-term protection against SARS-CoV-2 infection? A case-control study in Quebec, Canada

Vaccine. 2021 Dec 8;39(50):7300-7307. doi: 10.1016/j.vaccine.2021.08.019. Epub 2021 Aug 11.

Affiliations

¹ Department of Microbiology and Infectious Diseases, Université de Sherbrooke, 3001, 12ième Avenue Nord, Sherbrooke, Quebec J1H 5N4, Canada.
² Hôpital Maisonneuve-Rosemont - CIUSSS de l'Est-de-l'Ile-de-Montréal, 5415 Boulevard de l'Assomption, Montreal, Quebec H1T 2M4, Canada; Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Pavillon Roger-Gaudry, 2900 Boulevard Edouard Montpetit, Montreal, Quebec H3T 1J4, Canada.
³ Centre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, 531, boul. des Prairies, Laval, Quebec H7V 1B7, Canada.
⁴ Hôpital Maisonneuve-Rosemont - CIUSSS de l'Est-de-l'Ile-de-Montréal, 5415 Boulevard de l'Assomption, Montreal, Quebec H1T 2M4, Canada.
⁵ Department of Social and Preventive Medicine, Université Laval, 2725 Ch Ste-Foy, Quebec, Quebec G1V 4G5, Canada.
⁶ Centre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, 531, boul. des Prairies, Laval, Quebec H7V 1B7, Canada. Electronic address: marie-claude.rousseau@inrs.ca.

Abstract

Background: Early in the coronavirus disease 2019 (COVID-19) pandemic, before severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines became available, it was hypothesized that BCG (Bacillus Calmette-Guérin), which stimulates innate immunity, could provide protection against SARS-CoV-2. Numerous ecological studies, plagued by methodological deficiencies, revealed a country-level association between BCG use and lower COVID-19 incidence and mortality. We aimed to determine whether BCG administered in early life decreased the risk of SARS-CoV-2 infection in adulthood and the severity of COVID-19.

Methods: This case-control study was conducted in Quebec, Canada. Cases were patients with a positive SARS-CoV-2 nucleic acid amplification test performed at two hospitals between March-October 2020. Controls were identified among patients with non-COVID-19 samples processed by the same microbiology laboratories during the same period. Enrolment was limited to individuals born in Quebec between 1956 and 1976, whose vaccine status was accessible in a computerized registry of 4.2 million BCG vaccinations.

Results: We recruited 920 cases and 2123 controls. Fifty-four percent of cases (n = 424) and 53% of controls (n = 1127) had received BCG during childhood (OR: 1.03; 95% CI: 0.89-1.21), while 12% of cases (n = 114) and 11% of controls (n = 235) had received two or more BCG doses (OR: 1.14; 95% CI: 0.88-1.46). After adjusting for age, sex, material deprivation, recruiting hospital and occupation there was no evidence of protection conferred by BCG against SARS-CoV-2 (AOR: 1.01; 95% CI: 0.84-1.21). Among cases, 77 (8.4%) needed hospitalization and 18 (2.0%) died. The vaccinated were as likely as the unvaccinated to require hospitalization (AOR: 1.01, 95% CI: 0.62-1.67) or to die (AOR: 0.85, 95% CI: 0.32-2.39).

Conclusions: BCG does not provide long-term protection against symptomatic COVID-19 or severe forms of the disease.

Keywords: BCG; COVID-19; SARS-CoV-2; Vaccine effectiveness.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
BCG Vaccine
COVID-19*
Case-Control Studies
Humans
Quebec / epidemiology
SARS-CoV-2

Substances

BCG Vaccine