{Reference Type}: Journal Article
{Title}: BCG vaccination of healthcare workers for protection against COVID-19: 12-month outcomes from an international randomised controlled trial.
{Author}: Messina NL;Pittet LF;McDonald E;Moore C;Barry S;Bonten M;Byrne A;Campbell J;Croda J;Croda MG;Dalcolmo M;de Almeida E Val FF;de Oliveira RD;Dos Santos G;Douglas MW;Gardiner K;Gwee A;Jardim BA;Kollmann T;Lacerda MV;Lucas M;Lynn DJ;Manning L;Marshall H;O'Connell A;Perrett KP;Post JJ;Prat-Aymerich C;Rocha JL;Rodriguez-Baño J;Wadia U;Warris A;Davidson A;Curtis N; ;
{Journal}: J Infect
{Volume}: 89
{Issue}: 4
{Year}: 2024 Aug 8
{Factor}: 38.637
{DOI}: 10.1016/j.jinf.2024.106245
{Abstract}: <B>OBJECTIVE: </B>Bacille Calmette-Guérin (BCG) vaccine has immunomodulatory effects that may provide protection against unrelated infectious diseases. We aimed to determine whether BCG vaccination protects adults against COVID-19.<BR><B>METHODS: </B>Phase III double-blind randomised controlled trial.<BR><B>METHODS: </B>Healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom during the COVID-19 pandemic.<BR><B>METHODS: </B>3988 healthcare workers with no prior COVID-19 and no contraindication to BCG.<BR><B>METHODS: </B>Randomised 1:1 using a web-based procedure to receive a single 0.1 mL intradermal dose of BCG-Denmark (BCG group, n = 1999) or saline (placebo group, n = 1989).<BR><B>METHODS: </B>Difference in incidence of (i) symptomatic and (ii) severe COVID-19 during the 12 months following randomisation in the modified intention to treat (mITT) population (confirmed SARS-CoV-2 naïve at inclusion).<BR><B>RESULTS: </B>Of the 3988 participants randomised, 3386 had a negative baseline SARS-CoV-2 test and were included in the mITT population. The 12-month adjusted estimated risk of symptomatic COVID-19 was higher in the BCG group (22.6%; 95% confidence interval [CI] 20.6 to 24.5%) compared with the placebo group (19.6%; 95% CI 17.6 to 21.5%); adjusted difference +3.0% points (95% CI 0.2 to 5.8%; p = 0.04). The 12-month adjusted estimated risk of severe COVID-19 (mainly comprising those reporting being unable to work for ≥3 consecutive days) was 11.0% in the BCG group (95% CI 9.5 to 12.4%) compared with 9.6% in the placebo group (95% CI 8.3 to 11.1%); adjusted difference +1.3% points (95% CI -0.7 to 3.3%, p = 0.2). Breakthrough COVID-19 (post COVID-19 vaccination) and asymptomatic SARS-CoV-2 infections were similar in the two groups. There were 18 hospitalisations due to COVID-19 (11 in BCG group, 7 in placebo group; adjusted hazard ratio 1.56, 95% CI 0.60 to 4.02, p = 0.4) and two deaths due to COVID-19, both in the placebo group.<BR><B>CONCLUSIONS: </B>Compared to placebo, vaccination with BCG-Denmark increased the risk of symptomatic COVID-19 over 12 months among healthcare workers and did not decrease the risk of severe COVID-19 or post-vaccination breakthrough COVID-19.<BR><B>BACKGROUND: </B>ClinicalTrials.gov NCT04327206.