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

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...

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Main Authors: Joseph Inauen, Sam LaBroome, Antonietta Maldari, Natalie E. Stevens, James B. Geake, David J. Lynn, Simone Barry
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/3/267
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author Joseph Inauen
Sam LaBroome
Antonietta Maldari
Natalie E. Stevens
James B. Geake
David J. Lynn
Simone Barry
author_facet Joseph Inauen
Sam LaBroome
Antonietta Maldari
Natalie E. Stevens
James B. Geake
David J. Lynn
Simone Barry
author_sort Joseph Inauen
collection DOAJ
description 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, <i>p</i> = 0.335), COVID-19 incidence across all studies (relative risk 1.07, 0.94–1.21, <i>p</i> = 0.264), deaths reported in six studies (relative risk 0.67, 0.36–1.26, <i>p</i> = 0.733), and COVID-19-related critical care admissions reported in four studies (relative risk 0.43, 0.13–1.46, <i>p</i> = 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.
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spelling doaj-art-3121bcfb4ddc454db2804068e5fa7b3a2025-08-20T02:43:10ZengMDPI AGVaccines2076-393X2025-03-0113326710.3390/vaccines13030267Efficacy of Bacille Calmette–Guérin Against COVID-19 Hospitalisation: A Meta-Analysis and Systematic Review of Randomised Control TrialsJoseph Inauen0Sam LaBroome1Antonietta Maldari2Natalie E. Stevens3James B. Geake4David J. Lynn5Simone Barry6Royal Adelaide Hospital, Port Road, Adelaide, SA 5000, AustraliaRoyal Adelaide Hospital, Port Road, Adelaide, SA 5000, AustraliaRoyal Adelaide Hospital, Port Road, Adelaide, SA 5000, AustraliaPrecision Medicine Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, AustraliaRoyal Adelaide Hospital, Port Road, Adelaide, SA 5000, AustraliaPrecision Medicine Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, AustraliaRoyal Adelaide Hospital, Port Road, Adelaide, SA 5000, AustraliaBackground: 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, <i>p</i> = 0.335), COVID-19 incidence across all studies (relative risk 1.07, 0.94–1.21, <i>p</i> = 0.264), deaths reported in six studies (relative risk 0.67, 0.36–1.26, <i>p</i> = 0.733), and COVID-19-related critical care admissions reported in four studies (relative risk 0.43, 0.13–1.46, <i>p</i> = 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.https://www.mdpi.com/2076-393X/13/3/267BCGCOVID-19SARS-CoV-2systematic reviewmeta-analysis
spellingShingle Joseph Inauen
Sam LaBroome
Antonietta Maldari
Natalie E. Stevens
James B. Geake
David J. Lynn
Simone Barry
Efficacy of Bacille Calmette–Guérin Against COVID-19 Hospitalisation: A Meta-Analysis and Systematic Review of Randomised Control Trials
Vaccines
BCG
COVID-19
SARS-CoV-2
systematic review
meta-analysis
title Efficacy of Bacille Calmette–Guérin Against COVID-19 Hospitalisation: A Meta-Analysis and Systematic Review of Randomised Control Trials
title_full Efficacy of Bacille Calmette–Guérin Against COVID-19 Hospitalisation: A Meta-Analysis and Systematic Review of Randomised Control Trials
title_fullStr Efficacy of Bacille Calmette–Guérin Against COVID-19 Hospitalisation: A Meta-Analysis and Systematic Review of Randomised Control Trials
title_full_unstemmed Efficacy of Bacille Calmette–Guérin Against COVID-19 Hospitalisation: A Meta-Analysis and Systematic Review of Randomised Control Trials
title_short Efficacy of Bacille Calmette–Guérin Against COVID-19 Hospitalisation: A Meta-Analysis and Systematic Review of Randomised Control Trials
title_sort efficacy of bacille calmette guerin against covid 19 hospitalisation a meta analysis and systematic review of randomised control trials
topic BCG
COVID-19
SARS-CoV-2
systematic review
meta-analysis
url https://www.mdpi.com/2076-393X/13/3/267
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