COVID-19 pandemic: SARS-CoV-2 specific vaccines and challenges, protection via BCG trained immunity, and clinical trials

ABSTRACT

Introduction: The coronavirus disease 2019 (COVID-19) pandemic continues to spread worldwide and vaccination remains the most effective approach to control COVID-19. Currently, at least ten COVID-19 vaccines have been authorized under emergency authorization. However, these vaccines still face many challenges.

Areas covered: This study reviews the concept and mechanisms of trained immunity induced by the Bacille Calmette Guérin (BCG) vaccine and identifies questions that should be answered before the BCG vaccine could be used to combat COVID-19 pandemic. Moreover, we present for the first time the details of current BCG vaccine clinical trials, which are underway in various countries, to assess its effectiveness in combating the COVID-19 pandemic. Finally, we discuss the challenges of COVID-19 vaccines and opportunities for the BCG vaccine. The literature was found by searching the PubMed (https://pubmed.ncbi.nlm.nih.gov/), Web of Science (www.webofknowledge.com), Embase (https://www.embase.com), and CNKI (https://www.cnki.net/) databases. The date was set as the default parameter for each database.

Expert opinion: The advantages of the BCG vaccine can compensate for the shortcomings of other COVID-19 vaccines. If the efficacy of the BCG vaccine against COVID-19 is confirmed by these clinical trials, the BCG vaccine may be essential to resolve the challenges faced by COVID-19 vaccines.

KEYWORDS:

• Bacille Calmette-Guérin (BCG) vaccine
• SARS-COV-2
• COVID-19 pandemic
• trained immunity
• clinical trials

Article highlights

• At least ten COVID-19 vaccines have been authorized under an emergency use authorization (EUA) to prevent COVID-19 in more than 40 countries.

• These vaccines still face many challenges, such as the emergence of variant strains, public hesitation, poor cold chain logistics, and low production capacity.

• It is hypothesized that the BCG vaccine may stimulate a non-specific protective effect against COVID-19.

• The BCG vaccine has several advantages, including safety, accessibility, affordability, production capacity, transportation, storage, and distribution.

• To confirm this hypothesis, more than 51 clinical trials investigating the effectiveness of the BCG vaccine against COVID-19 have been conducted in various countries.

• Once this hypothesis is confirmed, the BCG vaccine may help solve the problems faced by the approved COVID-19 vaccines.

Acknowledgments

We would like to thank Editage (www.editage.cn) for English language editing.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was funded by the National Natural Science Foundation of China (Grant No: 81801643); Beijing Municipal Science & Technology Commission (Grant No: 19L2152); Chinese PLA General Hospital (Grant No: QNC19047); Finnish Cultural Foundation; Tampere Tuberculosis Foundation; Jane & Aatos Erkko Foundation; Finnish Foundation for Cardiovascular Research; and the Academy of Finland.