AUTHOR=Tsilika Maria , Taks Esther , Dolianitis Konstantinos , Kotsaki Antigone , Leventogiannis Konstantinos , Damoulari Christina , Kostoula Maria , Paneta Maria , Adamis Georgios , Papanikolaou Ilias , Stamatelopoulos Kimon , Bolanou Amalia , Katsaros Konstantinos , Delavinia Christina , Perdios Ioannis , Pandi Aggeliki , Tsiakos Konstantinos , Proios Nektarios , Kalogianni Emmanouela , Delis Ioannis , Skliros Efstathios , Akinosoglou Karolina , Perdikouli Aggeliki , Poulakou Garyfallia , Milionis Haralampos , Athanassopoulou Eva , Kalpaki Eleftheria , Efstratiou Leda , Perraki Varvara , Papadopoulos Antonios , Netea Mihai G. , Giamarellos-Bourboulis Evangelos J. 

TITLE=ACTIVATE-2: A Double-Blind Randomized Trial of BCG Vaccination Against COVID-19 in Individuals at Risk

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.873067

DOI=10.3389/fimmu.2022.873067

ISSN=1664-3224

ABSTRACT=In a recent study of our group with the acronym ACTIVATE, Bacillus Calmete- Guérin (BCG) vaccination reduced the occurrence of new infections compared to placebo vaccination in the elderly. Most benefit was found for respiratory infections. The ACTIVATE- II study was launched to assess the efficacy of BCG vaccination against COVID-19. In this multicenter, double- blind trial, 301 volunteers aged 50 years or older were randomized (1:1) to be vaccinated with BCG or placebo. The trial end points were the incidence of COVID-19 and presence of anti-SARS-CoV-2 antibodies, which were both evaluated through 6 months after study intervention. Results revealed 68% relative reduction of the risk to develop COVID-19, using clinical criteria or/and laboratory diagnosis, in the group of BCG-vaccine recipients compared with placebo-vaccinated controls, during a 6-months follow-up (OR 0.32, 95% CI 0.13-0.79). ). In total, eight patients were in need of hospitalization for COVID-19; six in the placebo group and two in the BCG group. Three months after study intervention, positive anti-SARS -CoV-2 antibodies were noted in 1.3% of volunteers in the placebo group and in 4.7% of participants in BCG-vaccinated group. These data indicate that BCG vaccination has a favorable safety profile and ensures protection against COVID-19 among elderly. BCG vaccination would be a promising approach against COVID-19 pandemic.