Efficacy of BCG Vaccination Against Respiratory Tract Infections in Older Adults During the Coronavirus Disease 2019 Pandemic

Abstract

Background Older age is associated with increased severity and death from respiratory infections, including coronavirus disease 2019 (Covid-19). The tuberculosis vaccine Bacille Calmette-Guérin (BCG) may provide heterologous protection against non-tuberculous infections, and has been proposed as a potential preventive strategy against Covid-19. Methods In this multicenter, placebo-controlled trial, we randomly assigned elderly individuals (60 years or older, n=2014) to intracutaneous vaccination with BCG (n=1008) or placebo (n=1006). The primary endpoint was the cumulative incidence of respiratory tract infections that required medical intervention, during 12 months of follow-up. Secondary endpoints included the incidence of Covid-19, and the effect of BCG vaccination on the cellular and humoral immune responses. Results The cumulative incidence of respiratory tract infection requiring medical intervention was 0.029 in the BCG-vaccinated group and 0.024 in the control group (subdistribution hazard ratio [SHR], 1.26; 98.2% confidence interval [CI], 0.65 to 2.44). 51 and 48 individuals tested positive for SARS-CoV-2 by PCR in the BCG and placebo group, respectively (SHR, 1.053; 95% CI, 0.71 to 1.56). No difference was observed in the frequency of adverse events. BCG vaccination was associated with enhanced cytokines responses after influenza, and partially also after SARS-CoV-2 stimulation. In patients diagnosed with Covid-19, antibody responses after infection were significantly stronger if the volunteers had previously received BCG. Conclusions BCG-vaccination had no effect on the incidence of respiratory tract infections, including SARS-CoV-2 infection, in elderly volunteers. However, BCG vaccination improved cytokine responses stimulated by influenza and SARS-CoV-2, and induced stronger antibody titers after Covid-19 infection.

Bacillus Calmette-Guérin vaccine to reduce healthcare worker absenteeism in COVID-19 pandemic, a randomized controlled trial

“…The ACTIVATE-2 randomized trial found a significantly reduced incidence of COVID-19 after BCG in frail elderly. 14 Parallel to the BCG-CORONA trial, we conducted two additional trials in elderly, the BCG-CORONA-ELDERLY trial, 15 and the BCG-PRIME trial (NCT04537663). Several additional BCG trials with COVID-19 endpoints are ongoing around the world, including the BRACE study (NCT04327206), and a real-time individual data meta-analysis is being conducted to monitor the effect of BCG on severe endpoints (PROSPERO ID: CRD42021213069).…”

Multiple BCG vaccinations for the prevention of COVID-19 and other infectious diseases in type 1 diabetes

“…With the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, some epidemiology studies began to uncover an association between neonatal BCG vaccination and reduced morbidity and mortality from COVID-19, even in older adults decades after the typical neonatal vaccinations, on a country-by-country basis. [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] In some other global populations with varying neonatal exposures, different BCG strains, and other populations, benefits were not observed. 24,[41][42][43][44][45][46][47] Because the United States has never vaccinated newborns or adults with BCG, a randomized trial of BCG for possible protection from SARS-CoV-2 infection offers a clean comparison in a vaccinenaive adult United States population.…”

Prospects on Repurposing a Live Attenuated Vaccine for the Control of Unrelated Infections

“…One randomized clinical trial showed that BCG vaccination in the elderly was correlated with lower incidence of SARS-CoV-2 infection ( 46 ). Yet other studies found no significant protective effect with BCG vaccination ( 121 – 123 ). Similarly, studies of COVID-19 in animal models also produced contradictory results.…”