Frontiers in Immunology (Jul 2022)
ACTIVATE-2: A Double-Blind Randomized Trial of BCG Vaccination Against COVID-19 in Individuals at Risk
- 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,
- Mihai G. Netea,
- Evangelos J. Giamarellos-Bourboulis,
- Evangelos J. Giamarellos-Bourboulis
Affiliations
- Maria Tsilika
- 4thDepartment of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece
- Esther Taks
- Department of Internal Medicine and Center for Infectious Diseases, Radboud University, Nijmegen, Netherlands
- Konstantinos Dolianitis
- Department of Internal Medicine, “Bodosakeio” General Hospital of Ptolemaida, Ptolemaida, Greece
- Antigone Kotsaki
- 4thDepartment of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece
- Konstantinos Leventogiannis
- 4thDepartment of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece
- Christina Damoulari
- 4thDepartment of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece
- Maria Kostoula
- 4thDepartment of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece
- Maria Paneta
- 4thDepartment of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece
- Georgios Adamis
- 1stDepartment of Internal Medicine, “G.Gennimatas” Athens General Hospital, Athens, Greece
- Ilias Papanikolaou
- Department of Pulmonary Medicine, Aghia Eirini General Hospital of Kerkyra, Kontokali, Greece
- Kimon Stamatelopoulos
- Department of Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
- Amalia Bolanou
- 4thDepartment of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece
- Konstantinos Katsaros
- Department of Surgery, General Hospital of Argos-Unit of Nafplion, Nafplion, Greece
- Christina Delavinia
- Department of Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
- Ioannis Perdios
- 1stDepartment of Internal Medicine, “G.Gennimatas” Athens General Hospital, Athens, Greece
- Aggeliki Pandi
- Department of Pulmonary Medicine, Aghia Eirini General Hospital of Kerkyra, Kontokali, Greece
- Konstantinos Tsiakos
- 3rdDepartment of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Nektarios Proios
- 4thDepartment of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece
- Emmanouela Kalogianni
- Department of Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
- Ioannis Delis
- Department of Internal Medicine, General Hospital of Karditsa, Karditsa, Greece
- Efstathios Skliros
- 0Nemea Health Center, Nemea, Greece
- Karolina Akinosoglou
- 1Department of Internal Medicine, Patras University Hospital, Rio, Greece
- Aggeliki Perdikouli
- 4thDepartment of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece
- Garyfallia Poulakou
- 3rdDepartment of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Haralampos Milionis
- 21stDepartment of Internal Medicine, University Hospital of Ioannina, Ioannina, Greece
- Eva Athanassopoulou
- 4thDepartment of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece
- Eleftheria Kalpaki
- 4thDepartment of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece
- Leda Efstratiou
- 3Hellenic Institute for the Study of Sepsis, Athens, Greece
- Varvara Perraki
- 3Hellenic Institute for the Study of Sepsis, Athens, Greece
- Antonios Papadopoulos
- 4thDepartment of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece
- Mihai G. Netea
- Department of Internal Medicine and Center for Infectious Diseases, Radboud University, Nijmegen, Netherlands
- Mihai G. Netea
- 4Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
- Evangelos J. Giamarellos-Bourboulis
- 4thDepartment of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece
- Evangelos J. Giamarellos-Bourboulis
- 3Hellenic Institute for the Study of Sepsis, Athens, Greece
- DOI
- https://doi.org/10.3389/fimmu.2022.873067
- Journal volume & issue
-
Vol. 13
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-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. The ACTIVATE II trial did not meet the primary endpoint of the reduction of the risk for COVID-19 3 months after BCG vaccination; however, the secondary endpoint of the reduction of the risk for COVID-19 6 months after BCG vaccination was met. BCG vaccination may be a promising approach against the COVID-19 pandemic.
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