Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers

Abstract

<div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="sc_a1"> <!-- named anchor --> </a> <h5 class="section-title" id="d741134e471">Background</h5> <p dir="auto" id="d741134e473">The bacille Calmette–Guérin (BCG) vaccine has immunomodulatory “off-target” effects that have been hypothesized to protect against coronavirus disease 2019 (Covid-19). </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="sc_a2"> <!-- named anchor --> </a> <h5 class="section-title" id="d741134e476">Methods</h5> <p dir="auto" id="d741134e478">In this international, double-blind, placebo-controlled trial, we randomly assigned health care workers to receive the BCG-Denmark vaccine or saline placebo and followed them for 12 months. Symptomatic Covid-19 and severe Covid-19, the primary outcomes, were assessed at 6 months; the primary analyses involved the modified intention-to-treat population, which was restricted to participants with a negative test for severe acute respiratory syndrome coronavirus 2 at baseline. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="sc_a3"> <!-- named anchor --> </a> <h5 class="section-title" id="d741134e481">Results</h5> <p dir="auto" id="d741134e483">A total of 3988 participants underwent randomization; recruitment ceased before the planned sample size was reached owing to the availability of Covid-19 vaccines. The modified intention-to-treat population included 84.9% of the participants who underwent randomization: 1703 in the BCG group and 1683 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. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="sc_a4"> <!-- named anchor --> </a> <h5 class="section-title" id="d741134e486">Conclusions</h5> <p dir="auto" id="d741134e488">Vaccination with BCG-Denmark did not result in a lower risk of Covid-19 among health care workers than placebo. (Funded by the Bill and Melinda Gates Foundation and others; BRACE ClinicalTrials.gov number, <a data-untrusted="" href="http://clinicaltrials.gov/show/NCT04327206" id="d741134e490" target="xrefwindow">NCT04327206</a>.) </p> </div>