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

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

BCG-PRIME study group

University Medical Center Utrecht
Radboud University Medical Center
Haga Ziekenhuis
Amsterdam UMC, Department of Radiation Oncology, The Netherlands
Onze Lieve Vrouwe Gasthuis
University of Bonn
Leiden University Medical Center
Noordwest Ziekenhuis
Catharina Hospital
Medisch Spectrum Twente
Canisius Wilhelmina Hospital
Rijnstate Hospital
Erasmus MC
Meander Medisch Centrum
Amsterdam UMC - Vrije Universiteit Amsterdam
Santeon
Martini Ziekenhuis
Department of Obstetrics and Gynaecology, Rotterdam, Netherlands
University of Groningen, University Medical Center Groningen
Maastricht UMC+
St. Antonius Ziekenhuis
Anticoagulation Clinic Leiden, Leiden, The Netherlands
Bernhoven Hospital, Uden, the Netherlands
Maasstad Hospital

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

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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
Early online date	2023
DOIs	https://doi.org/10.1016/j.cmi.2023.01.019
Publication status	Published - Jun 2023

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

BCG vaccine
Bacillus Calmette-Guérin vaccine
COVID-19
Randomized controlled trial
Respiratory tract infections

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@article{62fc9f7731df4cb7ae9206934624e809,

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 = "BCG vaccine, Bacillus Calmette-Gu{\'e}rin vaccine, COVID-19, Randomized controlled trial, Respiratory tract infections",

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 \{Aardenburg-van Huisstede\}, Astrid and Ammerlaan, \{Heidi S. M.\} and Boersma, \{Willem G.\} and Kees Brinkman and Bruijning-Verhagen, \{Patricia C. J.\} and \{van Crevel\}, Reinout and Corine Delsing and \{ten Doesschaten\}, Thijs and Dofferhoff, \{Anton S. M.\} and Ruud Duijkers and Groenwold, \{Rolf H. H.\} and \{de Haas\}, Corine and Robert-Jan Hassing and \{de Hoog\}, \{Marieke L. A.\} and Huijts, \{Susanne M.\} and \{van Hylckama-Vlieg\}, Astrid and Eefje Jong and \{de Jong\}, \{Hanna K.\} and Martijn Knap and Michael Koenders and Kouijzer, \{Ilse J. E.\} and Henk Kramer and \{van de Laar\}, Roel and Arief Lalmohamed and Lensen, \{Karel-Jan D. F.\} and Lijfering, \{Willem M.\} and Fabienne Magdelijns and Bob Meek and Middelburg, \{Rutger A.\} and Moeniralam, \{Hazra S.\} and Mooijaart, \{Simon P.\} and \{van Munster\}, \{Barbara C.\} and \{ten Oever\}, Jaap and Goossens, \{Marc Padros\} and Vincent Peters and Postma, \{Douwe F.\} and Niels Pouw and Reesink, \{Herre J.\} and \{de Regt\}, \{Marieke J. A.\} and \{van der Reijden\}, \{Anneli C. J.\} and R. Schaakxs and Kitty Slieker and \{BCG-PRIME study group\} and Slingerland, \{Robbert J.\} and \{van Sluis\}, \{Nicolette L. J.\} and Stehouwer, \{Coen D. A.\} and \{van de Veerdonk\}, Frank and Annelies Verbon and \{van Werkhoven\}, \{C. H. (Henri)\}",

note = "Funding Information: E.L.K. is the lead and corresponding author. J.S.v.d.M., C.v.N., J.J.H., M.A.A.J.v.d.B., M.G.N., F.R.R., M.J.M.B., and C.H.v.W. conceptualized the study. J.S.v.d.M., J.J.O., J.J.H., J.H.H.v.d.W., F.R.R., M.J.M.B., and C.H.v.W. developed methodology. J.S.v.d.M. was responsible for the software. C.H.v.W. performed the formal analysis. E.L.K., K.F., J.S.v.d.M., J.J.O., J.J.H., M.P.G., and C.H.v.W. performed the investigation. J.J.O., C.v.N., M.A.A.J.v.d.B., M.J.M.B., and C.H.v.W. were responsible for the resources. E.L.K., K.F., and C.H.v.W. were responsible for data curation. E.L.K., M.J.M.B., and C.H.v.W. wrote the original draft of the manuscript. E.L.K., K.F., J.S.v.d.M., C.v.N., M.P.G., J.H.H.v.d.W., M.G.N., F.R.R., M.J.M.B., and C.H.v.W. reviewed and edited the manuscript. E.L.K. and C.H.v.W. were responsible for visualization. J.S.v.d.M., J.J.O., M.P.G., M.A.A.J.v.d.B., J.H.H.v.d.W., M.G.N., F.R.R., M.J.M.B., and C.H.v.W. were responsible for supervision. E.L.K., K.F., J.S.v.d.M., J.J.H., F.R.R., and C.H.v.W. were responsible for project administration. J.J.H., J.H.H.v.d.W., M.A.A.J.v.d.B., F.R.R., M.G.N., M.J.M.B., and C.H.v.W. were responsible for funding acquisition. Publisher Copyright: {\textcopyright} 2023 The Author(s)",

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 Limited",

number = "6",

}

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 - Aardenburg-van Huisstede, Astrid

AU - Ammerlaan, Heidi S. M.

AU - Boersma, Willem G.

AU - Brinkman, Kees

AU - Bruijning-Verhagen, Patricia C. J.

AU - van Crevel, Reinout

AU - Delsing, Corine

AU - ten Doesschaten, Thijs

AU - Dofferhoff, Anton S. M.

AU - Duijkers, Ruud

AU - Groenwold, Rolf H. H.

AU - de Haas, Corine

AU - Hassing, Robert-Jan

AU - de Hoog, Marieke L. A.

AU - Huijts, Susanne M.

AU - van Hylckama-Vlieg, Astrid

AU - Jong, Eefje

AU - de Jong, Hanna K.

AU - Knap, Martijn

AU - Koenders, Michael

AU - Kouijzer, Ilse J. E.

AU - Kramer, Henk

AU - van de Laar, Roel

AU - Lalmohamed, Arief

AU - Lensen, Karel-Jan D. F.

AU - Lijfering, Willem M.

AU - Magdelijns, Fabienne

AU - Meek, Bob

AU - Middelburg, Rutger A.

AU - Moeniralam, Hazra S.

AU - Mooijaart, Simon P.

AU - van Munster, Barbara C.

AU - ten Oever, Jaap

AU - Goossens, Marc Padros

AU - Peters, Vincent

AU - Postma, Douwe F.

AU - Pouw, Niels

AU - Reesink, Herre J.

AU - de Regt, Marieke J. A.

AU - van der Reijden, Anneli C. J.

AU - Schaakxs, R.

AU - Slieker, Kitty

AU - BCG-PRIME study group

AU - Slingerland, Robbert J.

AU - van Sluis, Nicolette L. J.

AU - Stehouwer, Coen D. A.

AU - van de Veerdonk, Frank

AU - Verbon, Annelies

AU - van Werkhoven, C. H. (Henri)

N1 - Funding Information: E.L.K. is the lead and corresponding author. J.S.v.d.M., C.v.N., J.J.H., M.A.A.J.v.d.B., M.G.N., F.R.R., M.J.M.B., and C.H.v.W. conceptualized the study. J.S.v.d.M., J.J.O., J.J.H., J.H.H.v.d.W., F.R.R., M.J.M.B., and C.H.v.W. developed methodology. J.S.v.d.M. was responsible for the software. C.H.v.W. performed the formal analysis. E.L.K., K.F., J.S.v.d.M., J.J.O., J.J.H., M.P.G., and C.H.v.W. performed the investigation. J.J.O., C.v.N., M.A.A.J.v.d.B., M.J.M.B., and C.H.v.W. were responsible for the resources. E.L.K., K.F., and C.H.v.W. were responsible for data curation. E.L.K., M.J.M.B., and C.H.v.W. wrote the original draft of the manuscript. E.L.K., K.F., J.S.v.d.M., C.v.N., M.P.G., J.H.H.v.d.W., M.G.N., F.R.R., M.J.M.B., and C.H.v.W. reviewed and edited the manuscript. E.L.K. and C.H.v.W. were responsible for visualization. J.S.v.d.M., J.J.O., M.P.G., M.A.A.J.v.d.B., J.H.H.v.d.W., M.G.N., F.R.R., M.J.M.B., and C.H.v.W. were responsible for supervision. E.L.K., K.F., J.S.v.d.M., J.J.H., F.R.R., and C.H.v.W. were responsible for project administration. J.J.H., J.H.H.v.d.W., M.A.A.J.v.d.B., F.R.R., M.G.N., M.J.M.B., and C.H.v.W. were responsible for funding acquisition. Publisher Copyright: © 2023 The Author(s)

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 - BCG vaccine

KW - Bacillus Calmette-Guérin vaccine

KW - COVID-19

KW - Randomized controlled trial

KW - Respiratory tract infections

UR - https://www.scopus.com/pages/publications/85150018682

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 -

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

Abstract

UN SDGs

Keywords

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