ACTIVATE-2: A DOUBLE-BLIND RANDOMIZED TRIAL OF BCG VACCINATION AGAINST COVID19 IN INDIVIDUALS AT RISK

Tsilika, M.; Taks, E.; Dolianitis, K.; Kotsaki, A.; Leventogiannis, K.; Damoulari, C.; Kostoula, M.; Paneta, M.; Adamis, G.; Papanikolaou, I. C.; Stamatelopoulos, K.; Bolanou, A.; Katsaros, K.; Delavinia, C.; Perdios, I.; Pandi, A.; Tsiakos, K.; Proios, N.; Kalogianni, E.; Delis, I.; Skliros, E.; Akinosoglou, K.; Perdikouli, A.; Poulakou, G.; Milionis, H.; Athanasopoulou, E.; Kalpaki, E.; Efstratiou, L.; Perraki, V.; Papadopoulos, A.; Netea, M. G.; Giamarellos-Bourboulis, E.

BCG vaccination induces heterologous protection against respiratory tract infections, and in children improves survival independently of tuberculosis prevention. The phase III ACTIVATE-2 study assessed whether BCG could also protect against COVID19 in the elderly. In this double-blind, randomized trial, elderly Greek patients were randomized (1:1) to receive either BCG revaccination or placebo at hospital discharge, followed by 6 months observation for incidence of COVID19 infection. BCG revaccination resulted in 68% risk reduction for total COVID19 clinical and microbiological diagnoses (OR 0.32, 95% CI 0.13-0.79). Five patients in the placebo group and one in the BCG-vaccinated group had severe COVID19 that necessitated hospitalization. 3 months after BCG vaccination 1.3% of placebo and 4.7% of BCG-vaccinated volunteers had anti-SARS-CoV-2 antibodies. These data argue that BCG revaccination is safe and protects the elderly against COVID19. BCG revaccination may represent a viable preventive measure against COVID19.