The Bacille Calmette-Guérin (BCG) tuberculosis vaccine was not effective for preventing SARS-CoV-2 and other respiratory tract infections in older adults, according to results of a study published in Clinical Infectious Diseases.
Due to older individuals’ risk for increased severity and mortality from respiratory infections, researchers sought to assess the BCG vaccine’s protective effects in an older population. Researchers performed a multicenter, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT04417335) in 2014 adults aged 60 years and older to determine if the BCG vaccine could prevent COVID-19 infection or provide heterologous protection against nontuberculosis infections. Study participants were randomly assigned to receive either intracutaneous vaccination with BCG (n=1008) or placebo (n=1006). The cumulative incidence of respiratory tract infections requiring medical intervention during 12 months of follow-up was the primary endpoint. The incidence of COVID-19 and the vaccine effects on cellular and humoral immune responses were secondary endpoints.
The median patient age was 67 (IQR, 64-72) years, 47.5% were women, none of the patients had a medical history of SARS-CoV-2, and 29.2% of patients who received the BCG vaccine vs 25.4% who did not receive the BCG vaccine had a history of BCG vaccination before the study.
The cumulative incidence of infections satisfying the primary endpoint definition was 0.029 and 0.024 for the BCG-vaccinated and placebo groups, respectively (subdistribution hazard ratio [SHR], 1.26; 98.2% CI, 0.65-2.44). In the BCG-vaccinated vs placebo group, 51 and 48 patients tested positive for SARS-CoV-2, respectively (SHR, 1.053; 95% CI, 0.71-1.56).
There were no differences in the frequencies of adverse events. Researchers also observed an association between BCG vaccination and enhanced cytokines responses after influenza as well as a partial association after SARS-CoV-2 stimulation. Significantly stronger antibody responses were observed after infection in patients with a COVID-19 diagnosis and BCG vaccination.
Study limitations included the inability to completely blind the trial due to the local scar from BCG vaccination and an inability to perform baseline immune measurements and serology. Testing for COVID-19 was only available for health care workers and hospitalized patients at the beginning of the trial, suggesting that reported cases may be an underestimate. During the last 4 months of follow-up, most participants received at least 1 COVID-19 specific vaccine.
Researchers concluded, “While BCG vaccination was safe, only subtle (albeit statistically significant) effects on improvement of ex-vivo cytokine responses to influenza and SARS-CoV-2 were observed. However, BCG-vaccination improved IL-6 and humoral responses against SARS-CoV-2 after Covid-19, as compared to placebo.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Moorlag SJCFM, Taks E, ten Doesschate T, et al. Efficacy of Bacillus Calmette-Guérin vaccination against respiratory tract infections in the elderly during the Covid-19 pandemic. Clin Infect Dis. Published online March 5, 2022. doi:10.1093/cid/ciac182