ACTIVATE-2: A Double-Blind Randomized Trial of BCG Vaccination Against COVID-19 in Individuals at Risk
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
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.
Article activity feed
-
-
SciScore for 10.1101/2021.05.20.21257520: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:The present study also has limitations. The most important limitation is the small size of the study. Although the strong impact of BCG vaccination allowed to reach important conclusions regarding the effect on COVID-19, larger studies that are currently …
SciScore for 10.1101/2021.05.20.21257520: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:The present study also has limitations. The most important limitation is the small size of the study. Although the strong impact of BCG vaccination allowed to reach important conclusions regarding the effect on COVID-19, larger studies that are currently under way in different countries need to confirm the data of ACTIVATE-2. Another limitation is represented by the lack of microbiological testing in all patients with a clinical diagnosis of possible or probable COVID-19. Although we cannot exclude an alternative diagnosis is some of these patients, the context of the pandemic during tight societal restrictions makes COVID-19 diagnosis the most likely. Because of the small size of the study, no conclusions can be drawn regarding the effect of BCG vaccination on the severe forms of COVID-19, although the difference of hospitalizations between placebo and BCG groups suggests potential protection of the vaccination. A fourth limitation of the study is the lack of information regarding the SARS-CoV-2 strains that caused the infections in this study, and future studies need to investigate this aspect as well. Finally, we have limited information regarding the impact of BCG on the specific immunological host defense pathways against SARS-CoV-2 (specific antibodies and T-cell responses), and additional investigations should investigate these effects in more detail. When considering the availability of the novel specific anti-SARS-CoV-2 vaccines, one could ask why do we need trials i...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04414267 Completed Bacillus Calmette-guérin Vaccination to Prevent COVID-19 Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
-
