The immunomodulatory “off-target” effects of bacille Calmette–Guérin Denmark (BCG-Denmark) vaccine did not lower the risk of COVID-19 in health care workers in a placebo-controlled, international, double-blind trial. “Any effect on severe disease as defined by hospitalization or death could not be assessed,” the authors conclude. “It is important that our findings are not extrapolated beyond the effect of BCG-Denmark vaccine on Covid-19 in health care workers. Several studies show beneficial off-target effects of the BCG vaccine in other situations, particularly among infants in high-mortality geographic settings, and ongoing research is examining potential underlying immunologic mechanisms.”
Based on primary outcomes of symptomatic COVID-19 and severe COVID-19 at 6 months, this study showed: “The modified intention-to-treat population included 84.9% of the participants who underwent randomization: 1,703 in the BCG group and 1,683 in the placebo group. The estimated risk of symptomatic Covid-19 by 6 months was 14.7% in the BCG group and 12.3% in the placebo group (risk difference, 2.4 percentage points; 95% confidence interval [CI], −0.7 to 5.5; P = 0.13). The risk of severe Covid-19 by 6 months was 7.6% in the BCG group and 6.5% in the placebo group (risk difference, 1.1 percentage points; 95% CI, −1.2 to 3.5; P = 0.34); the majority of participants who met the trial definition of severe Covid-19 were not hospitalized but were unable to work for at least 3 consecutive days. In supplementary and sensitivity analyses that used less conservative censoring rules, the risk differences were similar but the confidence intervals were narrower. There were five hospitalizations due to Covid-19 in each group (including one death in the placebo group). The hazard ratio for any Covid-19 episode in the BCG group as compared with the placebo group was 1.23 (95% CI, 0.96 to 1.59). No safety concerns were identified.”