Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Jul 17;86(9):5439-5446.
doi: 10.1097/MS9.0000000000002370. eCollection 2024 Sep.

Efficacy and outcomes of BCG re-vaccination in COVID-19: a systematic review, meta-analysis, and meta-regression of randomized controlled trials

Hritvik Jain  1 , Ramez M Odat  2 , Ayham Mohammad Hussein  3 , Debankur Dey  4 , Mushood Ahmed  5 , Jyoti Jain  1 , Aman Goyal  6 , Tanya Ratnani  7 , Muhammad Idrees  8 , Priyadarshi Prajjwal  9 , Siddhant Passey  10 , Rukesh Yadav  11
Affiliations
Review

Efficacy and outcomes of BCG re-vaccination in COVID-19: a systematic review, meta-analysis, and meta-regression of randomized controlled trials

Hritvik Jain et al. Ann Med Surg (Lond). .

Abstract

Introduction: The Bacillus Calmette-Guerin (BCG) vaccine has a beneficial "off-target" effect that offers heterologous protection against respiratory tract infections by inducing trained immunity. The need for producing antigen-specific COVID-19 vaccines leads to delays in vaccine administration. Current randomized controlled trials (RCTs) report conflicting data on BCG's efficacy in COVID-19 infection.

Methods: A comprehensive literature search was conducted using major bibliographic databases to identify RCTs evaluating the outcomes of BCG re-vaccination in COVID-19. For dichotomous outcomes, odds ratios (ORs) with 95% CIs were pooled using the DerSimonian-Laird random-effects model. Statistical significance was set at P less than 0.05.

Results: Thirteen RCTs with 13 939 participants (7004 in the BCG re-vaccination group and 6935 in the placebo group) were included. BCG re-vaccination did not lead to a statistically significant difference in the incidence of COVID-19 infection [OR: 1.04; 95% CI: 0.91, 1.19; P=0.56], COVID-19-related hospitalizations [OR: 0.81; 95% CI: 0.38, 1.72; P=0.58), ICU admissions [OR: 0.43; 95% CI: 0.13, 1.46; P=0.18], or mortality [OR: 0.67; 95% CI 0.15, 3.04; P=0.60]. For safety outcomes, BCG re-vaccination led to a significant increase in the local injection site complications [OR: 99.79; 95% CI: 31.04, 320.80; P<0.00001], however, the risk of serious adverse events was similar [OR: 1.19; 95% CI: 0.84, 1.67; P=0.33].

Conclusions: BCG re-vaccination does not decrease the incidence of COVID-19 infection, COVID-19-related hospitalizations, ICU admissions, COVID-19-related mortality, and serious adverse events; however, it leads to a rise in local injection site complications. Caution should be exercised when overstating BCG's efficacy in COVID-19 prevention.

Keywords: BCG vaccine; COVID-19; SARS-CoV-2; coronavirus; vaccine.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Figures

None
Graphical abstract
Figure 1
Figure 1
Forest plots for pooled analyses comparing BCG re-vaccination to placebo. The odds ratios (ORs) with their 95% CIs are depicted on a logarithmic scale. The diamond symbolizes the combined or overall effect. (A) Incidence of COVID-19 infection; (B) COVID-19-related hospitalization; (C) COVID-19-related ICU admission; (D) COVID-19-related mortality; (E) Local injection site complications; (F) Serious adverse events. BCG, Bacillus Calmette-Guerin.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. COVID-19 Excess Mortality Collaborators . Estimating excess mortality due to the COVID-19 pandemic: a systematic analysis of COVID-19-related mortality, 2020-21. Lancet 2022;399:1513–1536. - PMC - PubMed
    1. Okafor CN, Rewane A, Momodu II. Bacillus Calmette Guerin. StatPearls. StatPearls Publishing; 2024. - PubMed
    1. Dos Santos PCP, Messina NL, de Oliveira RD, et al. . Effect of BCG vaccination against Mycobacterium tuberculosis infection in adult Brazilian health-care workers: a nested clinical trial. Lancet Infect Dis 2024;24:594–601. - PMC - PubMed
    1. Biering-Sørensen S, Aaby P, Lund N, et al. . Early BCG-denmark and neonatal mortality among infants weighing <2500 g: a randomized controlled trial. Clin Infect Dis 2017;65:1183–1190. - PMC - PubMed
    1. Arts RJW, Moorlag SJCFM, Novakovic B, et al. . BCG vaccination protects against experimental viral infection in humans through the induction of cytokines associated with trained immunity. Cell Host Microbe 2018;23:89–100.e5. - PubMed

LinkOut - more resources