BCG vaccine does not reduce risk of COVID-19 in healthcare workers

A recent study published in New England Journal of Medicine We evaluated whether the Bacillus Calmette-Guérin (BCG) vaccine can protect health care workers (HCW) from coronavirus disease 2019 (COVID-19).

the study: A randomized trial of the BCG vaccine to protect healthcare workers from Covid-19. Image Credit: ChompooSuriyo/Shutterstock.com

Background

The BCG vaccine has off-target immunomodulatory effects that may further protect against other infections. Vaccines are associated with a reduced risk of death from all causes in infants and a reduced risk of respiratory infections in adults/adolescents.

During the early COVID-19 pandemic, the repurposing of the BCG vaccine was proposed to protect against COVID-19. The hypothesis was that a vaccine might provide increased protection against SARS-CoV-2 until a vaccine against the pathogen became available.

About research

In the current study, researchers evaluated whether BCG vaccination reduces the incidence and severity of COVID-19 in healthcare workers in a randomized controlled trial. This study was conducted in his two stages.

Phase 1 recruited only Australian healthcare workers between March and May 2020. In the second phase, between May 2020 and April 2021, healthcare workers were recruited from Brazil, Spain, the Netherlands, and the United Kingdom.

If you have been previously positive for SARS-CoV-2, if you have been vaccinated with the BCG vaccine in the past year or any other live-attenuated vaccine in the past month, if you have participated in any other COVID-19 trial, or subjects were excluded if there were any contraindications to the BCG vaccine.

Double-blind Phase 2 participants were randomized to receive the BCG vaccine or saline placebo and were followed for 1 year.

The current analysis focused on the second stage, as community transmission of SARS-CoV-2 was negligible in the first stage. Blood samples were taken at baseline and every 3 months after randomization for serology.

Respiratory swab samples were also obtained from Brazilian healthcare workers for SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) assays.

Randomization was stratified by age group, geographic region, and presence or absence of comorbidities.

0.1 ml of BCG Denmark vaccine or placebo was injected intradermally. The primary outcome was the incidence of symptomatic COVID-19 and severe illness at 6 months after randomization.

Critical illness is a severely ill COVID-19 episode without hospitalization or death. Secondary endpoints were asymptomatic infection, time to COVID-19 onset, symptomatic days, days bedridden or absent from work, number of COVID-19 episodes, and complications.

findings

In Phase 2, 3,988 HCWs were randomized to receive the BCG vaccine or placebo. Baseline characteristics were similar between vaccine and placebo recipients, except for a slightly higher proportion of women in placebo recipients.

Most participants (64%) were recruited in Brazil. At baseline, 14% of his participants were positive for SARS-CoV-2 antibodies, and 2.7% of his swabs from Brazilian participants were positive for SARS-CoV-2.

Therefore, the revised intention-to-treat population included 1,703 subjects in the BCG group and 1,683 subjects in the placebo group. His symptomatic COVID-19 was documented in 132 of his BCG recipients and 106 of his placebo recipients. Severe COVID-19 occurred in 75 and her 61 subjects in the BCG and placebo groups, respectively.

Most of the severely ill were unable to work for at least three days. The probability of an episode of COVID-19 was higher in BCG recipients than in placebo participants, who experienced 5 hospitalizations in each group. Her BCG recipients aged 60 and older had fewer symptom days than the placebo group.

In the subgroup of HCWs without comorbidities, BCG recipients had fewer symptom days than placebo recipients. In the subset with comorbidities, the placebo recipient had fewer symptom days than her BCG recipient.

Twenty BCG participants and nine placebo recipients reported a total of 30 adverse events. Investigators considered all serious adverse events to be unrelated to the intervention.

Conclusion

Researchers found that the BCG vaccine did not reduce the risk of COVID-19 within 6 months after vaccination compared to placebo. Notably, the risk of a COVID-19 episode was higher in his BCG recipient than in placebo subjects.

More than one-third of participants had been previously vaccinated against BCG, suggesting that off-target effects may be higher in previously vaccinated subjects.

Moreover, (BCG) revaccination may not increase off-target benefits beyond those provided by previous vaccinations.

Interestingly, there was weak evidence of increased severe COVID-19 incidence in the BCG group, but not in previously unvaccinated but BCG revaccinated people. It did not reduce the risk of COVID-19 among healthcare workers and could not rule out a possible increased risk.