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Review
. 2025 Mar 4;13(3):267.
doi: 10.3390/vaccines13030267.

Efficacy of Bacille Calmette-Guérin Against COVID-19 Hospitalisation: A Meta-Analysis and Systematic Review of Randomised Control Trials

Joseph Inauen  1   2 , Sam LaBroome  1   2 , Antonietta Maldari  1 , Natalie E Stevens  3   4 , James B Geake  1 , David J Lynn  3   4 , Simone Barry  1   2   3
Affiliations
Review

Efficacy of Bacille Calmette-Guérin Against COVID-19 Hospitalisation: A Meta-Analysis and Systematic Review of Randomised Control Trials

Joseph Inauen et al. Vaccines (Basel). .

Abstract

Background: The BCG vaccine has long been hypothesised to have non-specific protective effects, and early epidemiological studies on COVID-19 suggested a possible protective effect against SARS-CoV-2 infection and COVID-19 severity. This systematic review and meta-analysis assesses the effect of the BCG vaccine on preventing severe COVID-19 disease, based on the rate of hospitalisation for COVID-19 related disease.

Methods: We performed a literature search of randomised control trials comparing BCG vaccine to placebo in adult participants using EMBASE, MEDLINE, and Web of Science. A random effects model was used to generate summary estimates. Risk of bias was assessed regarding randomisation, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases.

Results: We included 11 studies involving 18,412 participants, reporting COVID-19 incidence. The hospitalisation rate was sought from the authors of papers that did not report on this statistic. There was no significant reduction in COVID-19-related hospitalisation across all studies (relative risk 0.85, 0.51-1.40, p = 0.335), COVID-19 incidence across all studies (relative risk 1.07, 0.94-1.21, p = 0.264), deaths reported in six studies (relative risk 0.67, 0.36-1.26, p = 0.733), and COVID-19-related critical care admissions reported in four studies (relative risk 0.43, 0.13-1.46, p = 0.746).

Conclusions: The findings from this meta-analysis, involving a large number of participants, suggest no protective effect of BCG vaccination against severe COVID-19 outcomes or overall SARS-CoV-2 incidence. Further research may be needed to explore the potential non-specific effects of BCG vaccination in other specific populations and against other infections.

Keywords: BCG; COVID-19; SARS-CoV-2; meta-analysis; systematic review.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of the literature search and included studies.
Figure 2
Figure 2
Primary outcome—forest plot of COVID-19-related hospital admissions. Blossey 2023 [26], Koekenbier 2023 [27], Madsen 2024 [31], Moorlag 2022 [28], Pittet 2023 [32], Ramos-Martinez 2021 [33], Santos 2023 [34], Sinha 2022 [30], TenDoesschate 2022 [35], Tsilika 2022 [29], Upton 2022 [36].
Figure 3
Figure 3
Secondary outcomes—forest plots: (a) COVID-19 incidence; (b) COVID-19-related critical care admissions; (c) COVID-19 deaths. Forest plots depicting the relative risk (RR) and 95% confidence intervals (CI) for secondary outcomes. The random-effects model was used for analysis. Heterogeneity between studies was assessed using the I2 statistic. Blossey 2023 [26], Koekenbier 2023 [27]Madsen 2024 [31], Moorlag 2022 [28], Pittet 2023 [32], Ramos-Martinez 2021 [33], Santos 2023 [34], Sinha 2022 [30], TenDoesschate 2022 [35], Tsilika 2022 [29], Upton 2022 [36].
Figure 3
Figure 3
Secondary outcomes—forest plots: (a) COVID-19 incidence; (b) COVID-19-related critical care admissions; (c) COVID-19 deaths. Forest plots depicting the relative risk (RR) and 95% confidence intervals (CI) for secondary outcomes. The random-effects model was used for analysis. Heterogeneity between studies was assessed using the I2 statistic. Blossey 2023 [26], Koekenbier 2023 [27]Madsen 2024 [31], Moorlag 2022 [28], Pittet 2023 [32], Ramos-Martinez 2021 [33], Santos 2023 [34], Sinha 2022 [30], TenDoesschate 2022 [35], Tsilika 2022 [29], Upton 2022 [36].
Figure 4
Figure 4
(a): Funnel plot for COVID-19–related hospitalisations. A funnel plot assessing potential publication bias in studies reporting COVID-19–related hospitalisation. Symmetry suggests low risk of publication bias. (b): Eggers test for COVID-19–related hospitalisation. Egger’s regression test evaluating the presence of publication bias in studies reporting COVID-19-related hospitalisation. A p-value of 0.628 indicates low risk of bias.
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