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; Konstantin Fohse; Josephine S van de Maat; Jan Jelrik Oosterheert; Cees van Nieuwkoop; Jacobien J Hoogerwerf; Martin P Grobusch; Maurice A A J van den Bosch; Janneke H H van de Wijgert; Mihai G Netea; Frits R Rosendaal; Marc J M Bonten; C H Henri van Werkhoven; Fabienne Magdelijns; Coen Stehouwer; BCG-PRIME study group

doi:10.1016/j.cmi.2023.01.019

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^*, Konstantin Fohse, Josephine S van de Maat, Jan Jelrik Oosterheert, Cees van Nieuwkoop, Jacobien J Hoogerwerf, Martin P Grobusch, Maurice A A J van den Bosch, Janneke H H van de Wijgert, Mihai G Netea, Frits R Rosendaal, Marc J M Bonten, C H Henri van Werkhoven, Fabienne Magdelijns, Coen Stehouwer, BCG-PRIME study group

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	781-788
Number of pages	8
Journal	Clinical Microbiology and Infection
Volume	29
Issue number	6
DOIs	https://doi.org/10.1016/j.cmi.2023.01.019
Publication status	Published - Jun 2023

Keywords

Humans
Aged
COVID-19/epidemiology
BCG Vaccine
Vaccination
Hospitalization
Incidence

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Koekenbier, E. L., Fohse, K., van de Maat, J. S., Oosterheert, J. J., van Nieuwkoop, C., Hoogerwerf, J. J., Grobusch, M. P., van den Bosch, M. A. A. J., van de Wijgert, J. H. H., Netea, M. G., Rosendaal, F. R., Bonten, M. J. M., Werkhoven, C. H. H. V., Magdelijns, F., Stehouwer, C., & BCG-PRIME study group (2023). Bacillus Calmette-Guérin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial. Clinical Microbiology and Infection, 29(6), 781-788. https://doi.org/10.1016/j.cmi.2023.01.019

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title = "Bacillus Calmette-Gu{\'e}rin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial",

abstract = "OBJECTIVES: To test whether Bacillus Calmette-Gu{\'e}rin (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 = "Humans, Aged, COVID-19/epidemiology, BCG Vaccine, Vaccination, Hospitalization, Incidence",

author = "Koekenbier, {Eva L} and Konstantin Fohse and {van de Maat}, {Josephine S} and Oosterheert, {Jan Jelrik} and {van Nieuwkoop}, Cees and Hoogerwerf, {Jacobien J} and Grobusch, {Martin P} and {van den Bosch}, {Maurice A A J} and {van de Wijgert}, {Janneke H H} and Netea, {Mihai G} and Rosendaal, {Frits R} and Bonten, {Marc J M} and Werkhoven, {C H Henri van} and Fabienne Magdelijns and Coen Stehouwer and {BCG-PRIME study group}",

year = "2023",

month = jun,

doi = "10.1016/j.cmi.2023.01.019",

language = "English",

volume = "29",

pages = "781--788",

journal = "Clinical Microbiology and Infection",

issn = "1198-743X",

publisher = "ELSEVIER SCI LTD",

number = "6",

}

Koekenbier, EL, Fohse, K, van de Maat, JS, Oosterheert, JJ, van Nieuwkoop, C, Hoogerwerf, JJ, Grobusch, MP, van den Bosch, MAAJ, van de Wijgert, JHH, Netea, MG, Rosendaal, FR, Bonten, MJM, Werkhoven, CHHV, Magdelijns, F , Stehouwer, C & BCG-PRIME study group 2023, 'Bacillus Calmette-Guérin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial', Clinical Microbiology and Infection, vol. 29, no. 6, pp. 781-788. https://doi.org/10.1016/j.cmi.2023.01.019

Bacillus Calmette-Guérin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial. / Koekenbier, Eva L; Fohse, Konstantin; van de Maat, Josephine S et al.
In: Clinical Microbiology and Infection, Vol. 29, No. 6, 06.2023, p. 781-788.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Bacillus Calmette-Guérin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities

T2 - a randomized controlled trial

AU - Koekenbier, Eva L

AU - Fohse, Konstantin

AU - van de Maat, Josephine S

AU - Oosterheert, Jan Jelrik

AU - van Nieuwkoop, Cees

AU - Hoogerwerf, Jacobien J

AU - Grobusch, Martin P

AU - van den Bosch, Maurice A A J

AU - van de Wijgert, Janneke H H

AU - Netea, Mihai G

AU - Rosendaal, Frits R

AU - Bonten, Marc J M

AU - Werkhoven, C H Henri van

AU - Magdelijns, Fabienne

AU - Stehouwer, Coen

AU - BCG-PRIME study group

PY - 2023/6

Y1 - 2023/6

N2 - 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.

AB - 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.

KW - Humans

KW - Aged

KW - COVID-19/epidemiology

KW - BCG Vaccine

KW - Vaccination

KW - Hospitalization

KW - Incidence

U2 - 10.1016/j.cmi.2023.01.019

DO - 10.1016/j.cmi.2023.01.019

M3 - Article

C2 - 36736662

SN - 1198-743X

VL - 29

SP - 781

EP - 788

JO - Clinical Microbiology and Infection

JF - Clinical Microbiology and Infection

IS - 6

ER -