BCG Vaccination of Health Care Workers Does Not Reduce SARS-CoV-2 Infections nor Infection Severity or Duration: a Randomized Placebo-Controlled Trial
ABSTRACT Bacillus Calmette-Guerin (BCG) vaccination has been hypothesized to reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, severity, and/or duration via trained immunity induction. Health care workers (HCWs) in nine Dutch hospitals were randomized to BCG or placebo v...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-04-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.00356-23 |
| _version_ | 1827150271340347392 |
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| author | Juana Claus Thijs ten Doesschate Cheyenne Gumbs Cornelis H. van Werkhoven Thomas W. van der Vaart Axel B. Janssen Gaby Smits Rob van Binnendijk Fiona van der Klis Debbie van Baarle Fernanda L. Paganelli Helen Leavis Lilly M. Verhagen Simone A. Joosten Marc J. M. Bonten Mihai G. Netea Janneke H. H. M. van de Wijgert |
| author_facet | Juana Claus Thijs ten Doesschate Cheyenne Gumbs Cornelis H. van Werkhoven Thomas W. van der Vaart Axel B. Janssen Gaby Smits Rob van Binnendijk Fiona van der Klis Debbie van Baarle Fernanda L. Paganelli Helen Leavis Lilly M. Verhagen Simone A. Joosten Marc J. M. Bonten Mihai G. Netea Janneke H. H. M. van de Wijgert |
| author_sort | Juana Claus |
| collection | DOAJ |
| description | ABSTRACT Bacillus Calmette-Guerin (BCG) vaccination has been hypothesized to reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, severity, and/or duration via trained immunity induction. Health care workers (HCWs) in nine Dutch hospitals were randomized to BCG or placebo vaccination (1:1) in March and April 2020 and followed for 1 year. They reported daily symptoms, SARS-CoV-2 test results, and health care-seeking behavior via a smartphone application, and they donated blood for SARS-CoV-2 serology at two time points. A total of 1,511 HCWs were randomized and 1,309 analyzed (665 BCG and 644 placebo). Of the 298 infections detected during the trial, 74 were detected by serology only. The SARS-CoV-2 incidence rates were 0.25 and 0.26 per person-year in the BCG and placebo groups, respectively (incidence rate ratio, 0.95; 95% confidence interval, 0.76 to 1.21; P = 0.732). Only three participants required hospitalization for SARS-CoV-2. The proportions of participants with asymptomatic, mild, or moderate infections and the mean infection durations did not differ between randomization groups. In addition, unadjusted and adjusted logistic regression and Cox proportional hazards models showed no differences between BCG and placebo vaccination for any of these outcomes. The percentage of participants with seroconversion (7.8% versus 2.8%; P = 0.006) and mean SARS-CoV-2 anti-S1 antibody concentration (13.1 versus 4.3 IU/mL; P = 0.023) were higher in the BCG than placebo group at 3 months but not at 6 or 12 months postvaccination. BCG vaccination of HCWs did not reduce SARS-CoV-2 infections nor infection duration or severity (ranging from asymptomatic to moderate). In the first 3 months after vaccination, BCG vaccination may enhance SARS-CoV-2 antibody production during SARS-CoV-2 infection. IMPORTANCE While several BCG trials in adults were conducted during the 2019 coronavirus disease epidemic, our data set is the most comprehensive to date, because we included serologically confirmed infections in addition to self-reported positive SARS-CoV-2 test results. We also collected data on symptoms for every day during the 1-year follow-up period, which enabled us to characterize infections in detail. We found that BCG vaccination did not reduce SARS-CoV-2 infections nor infection duration or severity but may have enhanced SARS-CoV-2 antibody production during SARS-CoV-2 infection in the first 3 months after vaccination. These results are in agreement with other BCG trials that reported negative results (but did not use serological endpoints), except for two trials in Greece and India that reported positive results but had few endpoints and included endpoints that were not laboratory confirmed. The enhanced antibody production is in agreement with prior mechanistic studies but did not translate into protection from SARS-CoV-2 infection. |
| first_indexed | 2024-04-09T16:00:04Z |
| format | Article |
| id | doaj.art-de03d3eff55846609b67298b78f00f02 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2025-03-20T21:31:25Z |
| publishDate | 2023-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-de03d3eff55846609b67298b78f00f022024-08-11T18:27:32ZengAmerican Society for MicrobiologymBio2150-75112023-04-0114210.1128/mbio.00356-23BCG Vaccination of Health Care Workers Does Not Reduce SARS-CoV-2 Infections nor Infection Severity or Duration: a Randomized Placebo-Controlled TrialJuana Claus0Thijs ten Doesschate1Cheyenne Gumbs2Cornelis H. van Werkhoven3Thomas W. van der Vaart4Axel B. Janssen5Gaby Smits6Rob van Binnendijk7Fiona van der Klis8Debbie van Baarle9Fernanda L. Paganelli10Helen Leavis11Lilly M. Verhagen12Simone A. Joosten13Marc J. M. Bonten14Mihai G. Netea15Janneke H. H. M. van de Wijgert16Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsNational Institute of Public Health and the Environment, Bilthoven, NetherlandsNational Institute of Public Health and the Environment, Bilthoven, NetherlandsNational Institute of Public Health and the Environment, Bilthoven, NetherlandsNational Institute of Public Health and the Environment, Bilthoven, NetherlandsDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsDepartment of Internal Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsDepartment of Pediatric Infectious Diseases and Immunology, Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Infectious Diseases, Leiden University Medical Center, Leiden, NetherlandsJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsDepartment of Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, NetherlandsJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsABSTRACT Bacillus Calmette-Guerin (BCG) vaccination has been hypothesized to reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, severity, and/or duration via trained immunity induction. Health care workers (HCWs) in nine Dutch hospitals were randomized to BCG or placebo vaccination (1:1) in March and April 2020 and followed for 1 year. They reported daily symptoms, SARS-CoV-2 test results, and health care-seeking behavior via a smartphone application, and they donated blood for SARS-CoV-2 serology at two time points. A total of 1,511 HCWs were randomized and 1,309 analyzed (665 BCG and 644 placebo). Of the 298 infections detected during the trial, 74 were detected by serology only. The SARS-CoV-2 incidence rates were 0.25 and 0.26 per person-year in the BCG and placebo groups, respectively (incidence rate ratio, 0.95; 95% confidence interval, 0.76 to 1.21; P = 0.732). Only three participants required hospitalization for SARS-CoV-2. The proportions of participants with asymptomatic, mild, or moderate infections and the mean infection durations did not differ between randomization groups. In addition, unadjusted and adjusted logistic regression and Cox proportional hazards models showed no differences between BCG and placebo vaccination for any of these outcomes. The percentage of participants with seroconversion (7.8% versus 2.8%; P = 0.006) and mean SARS-CoV-2 anti-S1 antibody concentration (13.1 versus 4.3 IU/mL; P = 0.023) were higher in the BCG than placebo group at 3 months but not at 6 or 12 months postvaccination. BCG vaccination of HCWs did not reduce SARS-CoV-2 infections nor infection duration or severity (ranging from asymptomatic to moderate). In the first 3 months after vaccination, BCG vaccination may enhance SARS-CoV-2 antibody production during SARS-CoV-2 infection. IMPORTANCE While several BCG trials in adults were conducted during the 2019 coronavirus disease epidemic, our data set is the most comprehensive to date, because we included serologically confirmed infections in addition to self-reported positive SARS-CoV-2 test results. We also collected data on symptoms for every day during the 1-year follow-up period, which enabled us to characterize infections in detail. We found that BCG vaccination did not reduce SARS-CoV-2 infections nor infection duration or severity but may have enhanced SARS-CoV-2 antibody production during SARS-CoV-2 infection in the first 3 months after vaccination. These results are in agreement with other BCG trials that reported negative results (but did not use serological endpoints), except for two trials in Greece and India that reported positive results but had few endpoints and included endpoints that were not laboratory confirmed. The enhanced antibody production is in agreement with prior mechanistic studies but did not translate into protection from SARS-CoV-2 infection.https://journals.asm.org/doi/10.1128/mbio.00356-23SARS-CoV-2COVID-19Bacillus Calmette-Guerin vaccinerandomized placebo-controlled clinical trialhealth care workers |
| spellingShingle | Juana Claus Thijs ten Doesschate Cheyenne Gumbs Cornelis H. van Werkhoven Thomas W. van der Vaart Axel B. Janssen Gaby Smits Rob van Binnendijk Fiona van der Klis Debbie van Baarle Fernanda L. Paganelli Helen Leavis Lilly M. Verhagen Simone A. Joosten Marc J. M. Bonten Mihai G. Netea Janneke H. H. M. van de Wijgert BCG Vaccination of Health Care Workers Does Not Reduce SARS-CoV-2 Infections nor Infection Severity or Duration: a Randomized Placebo-Controlled Trial mBio SARS-CoV-2 COVID-19 Bacillus Calmette-Guerin vaccine randomized placebo-controlled clinical trial health care workers |
| title | BCG Vaccination of Health Care Workers Does Not Reduce SARS-CoV-2 Infections nor Infection Severity or Duration: a Randomized Placebo-Controlled Trial |
| title_full | BCG Vaccination of Health Care Workers Does Not Reduce SARS-CoV-2 Infections nor Infection Severity or Duration: a Randomized Placebo-Controlled Trial |
| title_fullStr | BCG Vaccination of Health Care Workers Does Not Reduce SARS-CoV-2 Infections nor Infection Severity or Duration: a Randomized Placebo-Controlled Trial |
| title_full_unstemmed | BCG Vaccination of Health Care Workers Does Not Reduce SARS-CoV-2 Infections nor Infection Severity or Duration: a Randomized Placebo-Controlled Trial |
| title_short | BCG Vaccination of Health Care Workers Does Not Reduce SARS-CoV-2 Infections nor Infection Severity or Duration: a Randomized Placebo-Controlled Trial |
| title_sort | bcg vaccination of health care workers does not reduce sars cov 2 infections nor infection severity or duration a randomized placebo controlled trial |
| topic | SARS-CoV-2 COVID-19 Bacillus Calmette-Guerin vaccine randomized placebo-controlled clinical trial health care workers |
| url | https://journals.asm.org/doi/10.1128/mbio.00356-23 |
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