J Korean Med Sci.  2023 Oct;38(42):e343. 10.3346/jkms.2023.38.e343.

Excluding Participants With Mycobacteria Infections From Clinical Trials: A Critical Consideration in Evaluating the Efficacy of BCG Against COVID-19

• Gong W
• Du J

• KMID: 2547560
• DOI: http://doi.org/10.3346/jkms.2023.38.e343

Abstract

In the context of the coronavirus disease 2019 (COVID-19) pandemic, Bacillus CalmetteGuérin (BCG), a tuberculosis (TB) vaccine, has been investigated for its potential to prevent COVID-19 with conflicting outcomes. Currently, over 50 clinical trials have been conducted to assess the effectiveness of BCG in preventing COVID-19, but the results have shown considerable variations. After scrutinizing the data, it was discovered that some trials had enrolled individuals with active TB, latent TB infection, or a history of TB. This finding raises concerns about the reliability and validity of the trial outcomes. In this study, we explore the potential consequences of including these participants in clinical trials, including impaired host immunity, immune exhaustion, and the potential masking of the BCG vaccine’s protective efficacy against COVID-19 by persistent mycobacterial infections. We also put forth several suggestions for future clinical trials. Our study underscores the criticality of excluding individuals with active or latent TB from clinical trials evaluating the efficacy of BCG in preventing COVID-19.

Keyword

Bacillus Calmette-Guérin (BCG); Coronavirus Disease 2019 (COVID-19); Active Tuberculosis (ATB); Latent Tuberculosis Infection (LTBI); Protection Efficacy

Figure

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  Fig. 1 BCG-induced trained immunity and the impact of acute and chronic MTB infection on its efficacy. The BCG-induced trained immunity relies on intercellular communication between various immune cells. The BCG vaccination stimulates innate immune cells to release inflammatory cytokines such as IL-1β, TNF-α, and IL-6, which in turn activate T cells and B cells for a more synchronized and effective response to subsequent infections, resulting in improved protection. However, acute and chronic MTB infections may impair immunity and exhaustion of T cells and mask the potential protective effects of the BCG vaccine.BCG = Bacillus Calmette-Guérin, DC = dendritic cells, SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2, TNF-α = tumor necrosis factor-α, IL = interleukin, PD-1 = programmed death 1, CTLA-4 = lymphocyte activation gene 3, and cytotoxic T lymphocyte antigen 4, Tim-3 = T-cell immunoglobulin and mucin structural domain protein 3, MTB = M. tuberculosis, ATB = active tuberculosis, LTBI = latent tuberculosis infection.

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