The effect of BCG vaccination on infection and antibody levels against SARS-CoV-2—The results of ProBCG: a multicenter randomized clinical trial in Brazil
Ana Paula Santos, Guilherme Loureiro Werneck, Ana Paula Razal Dalvi, Carla Conceição dos Santos, Paulo Fernando Guimarães Morando Marzocchi Tierno, Hanna Silva Condelo, Bruna Macedo, Janaina Aparecida de Medeiros Leung, Jeane de Souza Nogueira, Ludmila Malvão, Rafael Mello Galliez, Roberta Aguiar, Roberto Stefan, Sabrina Modena Knackfuss, Elisângela Silva, Terezinha Marta Pereira Pinto Castiñeiras, Roberto de Andrade Medronho, José Roberto Lapa e Silva, Rogério Rufino, Luís Cristóvão Pôrto, Luciana Silva Rodrigues, Afrânio Lineu Kritski, Fernanda Carvalho de Queiroz Mello
Abstract
OBJECTIVES: Evatuate if Bacillus Calmette-Guérin (BCG) vaccine could be used as a tool against SARS-CoV-2 based on the concept of trained immunity. METHODS: A multicenter, double-blinded, randomized clinical trial recruited health care workers (HCWs) in Brazil. The incidence rates of COVID-19, clinical manifestations, absenteeism, and adverse events among HCWs receiving BCG vaccine (Moreau or Moscow strains) or placebo were compared. BCG vaccine-mediated immune response before and after implementing specific vaccines for COVID-19 (CoronaVac or COVISHIELD) was analyzed. Cox proportional hazard and linear mixed effect modeling were used. RESULTS: A total of 264 volunteers were included for analysis (BCG = 134 and placebo = 130). The placebo group presented a COVID-19 cumulative incidence of 0.75% vs 0.52% of BCG. The Moreau strain also presented a higher incidence rate (1.60% × 0.22%). BCG did not show a protective hazard ratio against COVID-19. In addition, the log (immunoglobulin G) level against SARS-CoV-2 presented a higher increase in the BCG group, whether or not participants had COVID-19, but also without statistical significance. CONCLUSION: Our results suggest that BCG has a tendency of protection against SARS-CoV-2 and higher immunoglobulin G levels than placebo. The clinical trial was registered at https://clinicaltrials.gov/ (NCT04659941).