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 - BCG-PRIME study group
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 - Reesink, Herre J.
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 - http://www.scopus.com/inward/record.url?scp=85150018682&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.cmi.2023.01.019
DO - https://doi.org/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 -