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

Frontiers in immunology

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

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-2 study was launched to assess the efficacy of BCG vaccination against coronavirus disease 2019 (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 the presence of anti-severe acute respiratory syndrome coronavirus 2 (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-month 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 confers some protection against possible COVID-19 among patients older than 50 years with comorbidities. BCG vaccination may be a promising approach against the COVID-19 pandemic.

Copyright © 2022 Tsilika, Taks, Dolianitis, Kotsaki, Leventogiannis, Damoulari, Kostoula, Paneta, Adamis, Papanikolaou, Stamatelopoulos, Bolanou, Katsaros, Delavinia, Perdios, Pandi, Tsiakos, Proios, Kalogianni, Delis, Skliros, Akinosoglou, Perdikouli, Poulakou, Milionis, Athanassopoulou, Kalpaki, Efstratiou, Perraki, Papadopoulos, Netea and Giamarellos-Bourboulis.

PMID: 35865520

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