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.

The microbiology, epidemiology, diagnostics, and treatment of infective endocarditis (IE) have changed significantly since the Duke Criteria were published in 1994 and modified in 2000. The International Society for Cardiovascular Infectious Diseases (ISCVID) convened a multidisciplinary Working Group to update the diagnostic criteria for IE. The resulting 2023 Duke-ISCVID IE Criteria propose significant changes, including new microbiology diagnostics (enzyme immunoassay for Bartonella species, PCR, amplicon/metagenomic sequencing, in situ hybridization), imaging ([18F]FDG PET/CT, Cardiac Computed Tomography), and inclusion of intraoperative inspection as a new Major Clinical Criterion. The list of “typical” microorganisms causing IE was expanded and includes pathogens to be considered as typical only in the presence of intracardiac prostheses. The requirements for timing and separate venipunctures for blood cultures were removed. Last, additional predisposing conditions (transcatheter valve implants, endovascular cardiac implantable electronic devices, prior IE) were clarified. These diagnostic criteria should be updated periodically by making the ISCVID-Duke Criteria available online as a “Living Document”.

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