Another giant randomized trial of a bacillus Calmette-Guérin (BCG) vaccine as a way to thwart COVID-19 showed no benefit, the researchers reported.
In the multinational BRACE study, healthcare workers were also more likely to contract symptomatic COVID-19 for 6 months, regardless of whether they received a BCG-Denmark vaccine or placebo (14. 7% vs. 12. 3%, P = 0. 13), according to Nigel Curtis, MBBS, PhD, of the University of Melbourne in Australia, and colleagues.
In terms of severe disease, 7. 6% of patients in the vaccinated organization met the trial definition compared with 6. 5% of those in the placebo organization (P = . 34), the vast majority did not require hospitalization, the organization wrote in the New Journal of Medicine England.
The effects of the nearly 4,000-participant trial, which was conducted primarily before the widespread availability of COVID vaccines, “did not rule out the higher-risk option” with the BCG vaccine, the researchers said, but cautioned that they objected to extrapolating effects beyond trial parameters given the vaccine’s known benefits.
Why the BCG vaccine in the first place?
“In addition to opposing its target disease, tuberculosis, the [BCG] vaccine has ‘off-target’ immunomodulatory effects that would possibly oppose unrelated infections,” Curtis and colleagues explained.
Since previous studies showed a relief in all-cause deaths in infants and a lower risk of respiratory infections in older children and adults who received the BCG vaccine, at the beginning of the pandemic it was thought that it could be repurposed in place of the novel coronavirus.
“It has been hypothesized that the immunomodulatory properties of this vaccine would possibly oppose SARS-CoV-2, thus closing the gap until pathogen-specific vaccines are available,” the authors wrote.
Their findings mirror those of another large negative trial in older adults with comorbidities, but point to a number of conflicting studies involving BCG vaccination for COVID-19.
BRACE (BCG vaccination to reduce the impact of COVID-19 on health workers) was a double-blind trial conducted at 36 sites in five countries (Brazil, Australia, the Netherlands, the United Kingdom and Spain). A total of 3988 participants were randomized 1:1 to obtain either BCG-Denmark vaccine or saline placebo. The trial was first introduced in March 2020 and continued until April 2021, but recruitment was eventually halted following the availability of COVID vaccines.
A modified intent-to-treat (mITT) population limited to SARS-CoV-2 prestige negative participants at baseline used for the number one analyses, leaving 1703 in the vaccine arm and 1683 in the placebo arm. The number one results were symptomatic COVID disease or severe illness, the latter explained as any COVID-related hospitalization or death, as well as cases where patients were in poor enough health that they could not work for 3 or more consecutive days.
Participants in the mITT population had an average age of 43 years, approximately three-quarters were women, 20% had comorbidities (diabetes, central disease/hypertension, or chronic respiratory disease), and 21% were obese. The majority (74%) had earned a BCG vaccine at some point in their lives.
During the 6 months, 132 cases of symptomatic COVID-19 occurred in the BCG vaccine organization compared to 106 in the placebo organization, with severe cases in 75 and 61, respectively. Most participants who met the definition of severe disease did not require hospitalization. ; However, 71% were too ill to move on to paintings and 22% were too ill to get out of bed.
No significant differences were observed for a multitude of secondary outcomes, adding COVID-19 pneumonia (seven cases in the arm) and COVID hospitalization (five in the arm), among others. One player in the placebo arm died of COVID-19.
The differences between the teams were small, but the maximum effects showed a slight trend in favor of placebo, and the only indication of benefit with the BCG vaccine gave the impression in the post-hoc analyses: a faster recovery time in other people over 60. and where co-existing conditions do not.
Curtis and co-authors recommended several conceivable points that would possibly have affected the side effects of the BCG vaccine, adding “the predominance of female participants (in whom it is proposed that side effects differ from those of men) and the underrepresentation of participants who had not in the past won BCG vaccine. “
There were no known protection considerations in the trial, with serious adverse events reported in 20 participants in the BCG organisation and in the placebo organisation.
The main limitations cited by the researchers were the inability to fully enroll in the intended trial size, the definition used for severe COVID-19 (which now sometimes refers to COVID-related hospitalization or death), and the fact that blinding is complicated with BCG. . vaccine due to injection site reactions, although they tried to mitigate the latter by telling participants that vaccination does not cause a reaction.
Ian Ingram is editor-in-chief of MedPage Today and is helping to cover the site’s oncology.
The trial was funded through the Bill and Melinda Gates Foundation, among others.
Curtis revealed something. Co-authors reported relationships with Aravax, DBV Technologies, Merck, Novartis, the National Institute of Allergy and Infectious Diseases, the National Board of Health and Medical Research, the Sabin Vaccine Institute, Sanofi Pasteur, Siolta, and Valneva Austria GmbH.