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

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

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 polymerase chain reaction assay 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.