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Randomized Controlled Trial
. 2023 Jun;29(6):781-788.
doi: 10.1016/j.cmi.2023.01.019. Epub 2023 Feb 2.

Bacillus Calmette-Guérin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial

Eva L Koekenbier  1 , Konstantin Fohse  2 , Josephine S van de Maat  2 , Jan Jelrik Oosterheert  3 , Cees van Nieuwkoop  4 , Jacobien J Hoogerwerf  2 , Martin P Grobusch  5 , Maurice A A J van den Bosch  6 , Janneke H H van de Wijgert  7 , Mihai G Netea  8 , Frits R Rosendaal  9 , Marc J M Bonten  7 , C H Henri van Werkhoven  7 ; BCG-PRIME study group
Collaborators, Affiliations
Randomized Controlled Trial

Bacillus Calmette-Guérin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial

Eva L Koekenbier et al. Clin Microbiol Infect. 2023 Jun.

Abstract

Objectives: To test whether Bacillus Calmette-Guérin (BCG) vaccination would reduce the incidence of COVID-19 and other respiratory tract infections (RTIs) in older adults with one or more comorbidities.

Methods: Community-dwelling adults aged 60 years or older with one or more underlying comorbidities and no contraindications to BCG vaccination were randomized 1:1 to BCG or placebo vaccination and followed for 6 months. The primary endpoint was a self-reported, test-confirmed COVID-19 incidence. Secondary endpoints included COVID-19 hospital admissions and clinically relevant RTIs (i.e. RTIs including but not limited to COVID-19 requiring medical intervention). COVID-19 and clinically relevant RTI episodes were adjudicated. Incidences were compared using Fine-Gray regression, accounting for competing events.

Results: A total of 6112 participants with a median age of 69 years (interquartile range, 65-74) and median of 2 (interquartile range, 1-3) comorbidities were randomized to BCG (n = 3058) or placebo (n = 3054) vaccination. COVID-19 infections were reported by 129 BCG recipients compared to 115 placebo recipients [hazard ratio (HR), 1.12; 95% CI, 0.87-1.44]. COVID-19-related hospitalization occurred in 18 BCG and 21 placebo recipients (HR, 0.86; 95% CI, 0.46-1.61). During the study period, 13 BCG recipients died compared with 18 placebo recipients (HR, 0.71; 95% CI, 0.35-1.43), of which 11 deaths (35%) were COVID-19-related: six in the placebo group and five in the BCG group. Clinically relevant RTI was reported by 66 BCG and 72 placebo recipients (HR, 0.92; 95% CI, 0.66-1.28).

Discussion: BCG vaccination does not protect older adults with comorbidities against COVID-19, COVID-19 hospitalization, or clinically relevant RTIs.

Keywords: BCG vaccine; Bacillus Calmette-Guérin vaccine; COVID-19; Randomized controlled trial; Respiratory tract infections.

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Figures

Fig. 1
Fig. 1
Flowchart. ∗ A total of 1509 non-inclusions were recorded in 12 hospitals. These hospitals together enrolled 4451 participants in the study. Other participating hospitals did not keep a record of screened patients.
Fig. 2
Fig. 2
Cumulative incidence function of primary and secondary endpoints. (A) COVID-19, (B) documented asymptomatic SARS-CoV-2 infection, (C) mild-moderate SARS-CoV-2 infection, (D) COVID-19-related hospitalization, (E) clinically relevant RTI, and (F) clinically relevant RTI excluding COVID-19.
See this image and copyright information in PMC

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