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

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.