Using BCG vaccine to enhance non-specific protection of health care workers during the COVID-19 pandemic: A structured summary of a study protocol for a randomised controlled trial in Denmark
The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and significant reductions in all-cause morbidity and mortality have been reported. We aim to test whether BCG vaccination may reduce susceptibility to and/or...
Saved in:
| Published in | Current controlled trials in cardiovascular medicine Vol. 21; no. 1; pp. 799 - 3 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
BioMed Central Ltd
17.09.2020
BioMed Central BMC |
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and significant reductions in all-cause morbidity and mortality have been reported. We aim to test whether BCG vaccination may reduce susceptibility to and/or the severity of COVID-19 and other infectious diseases in health care workers (HCW) and thus prevent work absenteeism.The primary objective is to reduce absenteeism due to illness among HCW during the COVID-19 pandemic. The secondary objectives are to reduce the number of HCW that are infected with SARS-CoV-2, and to reduce the number of hospital admissions among HCW during the COVID-19 pandemic.
BCG vaccination of HCW will reduce absenteeism by 20% over a period of 6 months.
Placebo-controlled, single-blinded, randomised controlled trial, recruiting study participants at several geographic locations. The BCG vaccine is used in this study on a different indication than the one it has been approved for by the Danish Medicines Agency, therefore this is classified as a phase III study.
The trial will recruit 1,500 HCW at Danish hospitals.To be eligible for participation, a subject must meet the following criteria: Adult (≥18 years); Hospital personnel working at a participating hospital for more than 22 hours per week.A potential subject who meets any of the following criteria will be excluded from participation in this study: Known allergy to components of the BCG vaccine or serious adverse events to prior BCG administration Known prior active or latent infection with Mycobacterium tuberculosis (M. tuberculosis) or other mycobacterial species Previous confirmed COVID-19 Fever (>38 C) within the past 24 hours Suspicion of active viral or bacterial infection Pregnancy Breastfeeding Vaccination with other live attenuated vaccine within the last 4 weeks Severely immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1) b) subjects with solid organ transplantation c) subjects with bone marrow transplantation d) subjects under chemotherapy e) subjects with primary immunodeficiency f) subjects under treatment with any anti-cytokine therapy within the last year g) subjects under treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months h) Active solid or non-solid malignancy or lymphoma within the prior two years Direct involvement in the design or the execution of the BCG-DENMARK-COVID trial Intervention and comparator: Participants will be randomised to BCG vaccine (BCG-Denmark, AJ Vaccines, Copenhagen, Denmark) or placebo (saline). An adult dose of 0.1 ml of resuspended BCG vaccine (intervention) or 0.1 ml of sterile 0.9% NaCl solution (control) is administered intradermally in the upper deltoid area of the right arm. All participants will receive one injection at inclusion, and no further treatment of study participants will take place.
Main study endpoint: Days of unplanned absenteeism due to illness within 180 days of randomisation.Secondary study endpoints: The cumulative incidence of documented COVID-19 and the cumulative incidence of hospital admission for any reason within 180 days of randomisation.Randomisation: Randomisation will be done centrally using the REDCap tool with stratification by hospital, sex and age groups (+/- 45 years of age) in random blocks of 4 and 6. The allocation ratio is 1:1.Blinding (masking): Participants will be blinded to treatment. The participant will be asked to leave the room while the allocated treatment is prepared. Once ready for injection, vaccine and placebo will look similar, and the participant will not be able to tell the difference.The physicians administering the treatment are not blinded.Numbers to be randomised (sample size): Sample size: N=1,500. The 1,500 participants will be randomised 1:1 to BCG or placebo with 750 participants in each group.Trial Status: Current protocol version 5.1, from July 6, 2020.Recruitment of study participants started on May 18, 2020 and we anticipate having finished recruiting by the end of December 2020.
The trial was registered with EudraCT on April 16, 2020, EudraCT number: 2020-001888-90, and with ClinicalTrials.gov on May 1, 2020, registration number NCT04373291.Full protocol: The full protocol is attached as an additional file, accessible from the Trialswebsite (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. |
|---|---|
| AbstractList | Abstract Objectives: The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and significant reductions in all-cause morbidity and mortality have been reported. We aim to test whether BCG vaccination may reduce susceptibility to and/or the severity of COVID-19 and other infectious diseases in health care workers (HCW) and thus prevent work absenteeism. The primary objective is to reduce absenteeism due to illness among HCW during the COVID-19 pandemic. The secondary objectives are to reduce the number of HCW that are infected with SARS-CoV-2, and to reduce the number of hospital admissions among HCW during the COVID-19 pandemic. Hypothesis: BCG vaccination of HCW will reduce absenteeism by 20% over a period of 6 months. Trial design: Placebo-controlled, single-blinded, randomised controlled trial, recruiting study participants at several geographic locations. The BCG vaccine is used in this study on a different indication than the one it has been approved for by the Danish Medicines Agency, therefore this is classified as a phase III study. Participants: The trial will recruit 1,500 HCW at Danish hospitals. To be eligible for participation, a subject must meet the following criteria: Adult (≥18 years); Hospital personnel working at a participating hospital for more than 22 hours per week. A potential subject who meets any of the following criteria will be excluded from participation in this study: Known allergy to components of the BCG vaccine or serious adverse events to prior BCG administration Known prior active or latent infection with Mycobacterium tuberculosis (M. tuberculosis) or other mycobacterial species Previous confirmed COVID-19 Fever (>38 C) within the past 24 hours Suspicion of active viral or bacterial infection Pregnancy Breastfeeding Vaccination with other live attenuated vaccine within the last 4 weeks Severely immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1) b) subjects with solid organ transplantation c) subjects with bone marrow transplantation d) subjects under chemotherapy e) subjects with primary immunodeficiency f) subjects under treatment with any anti-cytokine therapy within the last year g) subjects under treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months h) Active solid or non-solid malignancy or lymphoma within the prior two years Direct involvement in the design or the execution of the BCG-DENMARK-COVID trial Intervention and comparator: Participants will be randomised to BCG vaccine (BCG-Denmark, AJ Vaccines, Copenhagen, Denmark) or placebo (saline). An adult dose of 0.1 ml of resuspended BCG vaccine (intervention) or 0.1 ml of sterile 0.9% NaCl solution (control) is administered intradermally in the upper deltoid area of the right arm. All participants will receive one injection at inclusion, and no further treatment of study participants will take place. Main outcomes: Main study endpoint: Days of unplanned absenteeism due to illness within 180 days of randomisation. Secondary study endpoints: The cumulative incidence of documented COVID-19 and the cumulative incidence of hospital admission for any reason within 180 days of randomisation. Randomisation: Randomisation will be done centrally using the REDCap tool with stratification by hospital, sex and age groups (+/- 45 years of age) in random blocks of 4 and 6. The allocation ratio is 1:1. Blinding (masking): Participants will be blinded to treatment. The participant will be asked to leave the room while the allocated treatment is prepared. Once ready for injection, vaccine and placebo will look similar, and the participant will not be able to tell the difference. The physicians administering the treatment are not blinded. Numbers to be randomised (sample size): Sample size: N=1,500. The 1,500 participants will be randomised 1:1 to BCG or placebo with 750 participants in each group. Trial Status: Current protocol version 5.1, from July 6, 2020. Recruitment of study participants started on May 18, 2020 and we anticipate having finished recruiting by the end of December 2020. Trial registration: The trial was registered with EudraCT on April 16, 2020, EudraCT number: 2020-001888-90, and with ClinicalTrials.gov on May 1, 2020, registration number NCT04373291. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Keywords: COVID-19, Randomised controlled trial, Protocol, BCG vaccine, NSEs/Non-specific effects of vaccines, Heterologous effects of vaccines, Health care workers, Pandemic, Immune training. The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and significant reductions in all-cause morbidity and mortality have been reported. We aim to test whether BCG vaccination may reduce susceptibility to and/or the severity of COVID-19 and other infectious diseases in health care workers (HCW) and thus prevent work absenteeism.The primary objective is to reduce absenteeism due to illness among HCW during the COVID-19 pandemic. The secondary objectives are to reduce the number of HCW that are infected with SARS-CoV-2, and to reduce the number of hospital admissions among HCW during the COVID-19 pandemic. BCG vaccination of HCW will reduce absenteeism by 20% over a period of 6 months. Placebo-controlled, single-blinded, randomised controlled trial, recruiting study participants at several geographic locations. The BCG vaccine is used in this study on a different indication than the one it has been approved for by the Danish Medicines Agency, therefore this is classified as a phase III study. The trial will recruit 1,500 HCW at Danish hospitals.To be eligible for participation, a subject must meet the following criteria: Adult (≥18 years); Hospital personnel working at a participating hospital for more than 22 hours per week.A potential subject who meets any of the following criteria will be excluded from participation in this study: Known allergy to components of the BCG vaccine or serious adverse events to prior BCG administration Known prior active or latent infection with Mycobacterium tuberculosis (M. tuberculosis) or other mycobacterial species Previous confirmed COVID-19 Fever (>38 C) within the past 24 hours Suspicion of active viral or bacterial infection Pregnancy Breastfeeding Vaccination with other live attenuated vaccine within the last 4 weeks Severely immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1) b) subjects with solid organ transplantation c) subjects with bone marrow transplantation d) subjects under chemotherapy e) subjects with primary immunodeficiency f) subjects under treatment with any anti-cytokine therapy within the last year g) subjects under treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months h) Active solid or non-solid malignancy or lymphoma within the prior two years Direct involvement in the design or the execution of the BCG-DENMARK-COVID trial Intervention and comparator: Participants will be randomised to BCG vaccine (BCG-Denmark, AJ Vaccines, Copenhagen, Denmark) or placebo (saline). An adult dose of 0.1 ml of resuspended BCG vaccine (intervention) or 0.1 ml of sterile 0.9% NaCl solution (control) is administered intradermally in the upper deltoid area of the right arm. All participants will receive one injection at inclusion, and no further treatment of study participants will take place. Main study endpoint: Days of unplanned absenteeism due to illness within 180 days of randomisation.Secondary study endpoints: The cumulative incidence of documented COVID-19 and the cumulative incidence of hospital admission for any reason within 180 days of randomisation.Randomisation: Randomisation will be done centrally using the REDCap tool with stratification by hospital, sex and age groups (+/- 45 years of age) in random blocks of 4 and 6. The allocation ratio is 1:1.Blinding (masking): Participants will be blinded to treatment. The participant will be asked to leave the room while the allocated treatment is prepared. Once ready for injection, vaccine and placebo will look similar, and the participant will not be able to tell the difference.The physicians administering the treatment are not blinded.Numbers to be randomised (sample size): Sample size: N=1,500. The 1,500 participants will be randomised 1:1 to BCG or placebo with 750 participants in each group.Trial Status: Current protocol version 5.1, from July 6, 2020.Recruitment of study participants started on May 18, 2020 and we anticipate having finished recruiting by the end of December 2020. The trial was registered with EudraCT on April 16, 2020, EudraCT number: 2020-001888-90, and with ClinicalTrials.gov on May 1, 2020, registration number NCT04373291.Full protocol: The full protocol is attached as an additional file, accessible from the Trialswebsite (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Objectives: The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and significant reductions in all-cause morbidity and mortality have been reported. We aim to test whether BCG vaccination may reduce susceptibility to and/or the severity of COVID-19 and other infectious diseases in health care workers (HCW) and thus prevent work absenteeism. The primary objective is to reduce absenteeism due to illness among HCW during the COVID-19 pandemic. The secondary objectives are to reduce the number of HCW that are infected with SARS-CoV-2, and to reduce the number of hospital admissions among HCW during the COVID-19 pandemic. Hypothesis: BCG vaccination of HCW will reduce absenteeism by 20% over a period of 6 months. Trial design: Placebo-controlled, single-blinded, randomised controlled trial, recruiting study participants at several geographic locations. The BCG vaccine is used in this study on a different indication than the one it has been approved for by the Danish Medicines Agency, therefore this is classified as a phase III study. Participants: The trial will recruit 1,500 HCW at Danish hospitals. To be eligible for participation, a subject must meet the following criteria: Adult ([greater than or equai to]18 years); Hospital personnel working at a participating hospital for more than 22 hours per week. A potential subject who meets any of the following criteria will be excluded from participation in this study: Known allergy to components of the BCG vaccine or serious adverse events to prior BCG administration Known prior active or latent infection with Mycobacterium tuberculosis (M. tuberculosis) or other mycobacterial species Previous confirmed COVID-19 Fever (>38 C) within the past 24 hours Suspicion of active viral or bacterial infection Pregnancy Breastfeeding Vaccination with other live attenuated vaccine within the last 4 weeks Severely immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1) b) subjects with solid organ transplantation c) subjects with bone marrow transplantation d) subjects under chemotherapy e) subjects with primary immunodeficiency f) subjects under treatment with any anti-cytokine therapy within the last year g) subjects under treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months h) Active solid or non-solid malignancy or lymphoma within the prior two years Direct involvement in the design or the execution of the BCG-DENMARK-COVID trial Intervention and comparator: Participants will be randomised to BCG vaccine (BCG-Denmark, AJ Vaccines, Copenhagen, Denmark) or placebo (saline). An adult dose of 0.1 ml of resuspended BCG vaccine (intervention) or 0.1 ml of sterile 0.9% NaCl solution (control) is administered intradermally in the upper deltoid area of the right arm. All participants will receive one injection at inclusion, and no further treatment of study participants will take place. Main outcomes: Main study endpoint: Days of unplanned absenteeism due to illness within 180 days of randomisation. Secondary study endpoints: The cumulative incidence of documented COVID-19 and the cumulative incidence of hospital admission for any reason within 180 days of randomisation. Randomisation: Randomisation will be done centrally using the REDCap tool with stratification by hospital, sex and age groups (+/- 45 years of age) in random blocks of 4 and 6. The allocation ratio is 1:1. Blinding (masking): Participants will be blinded to treatment. The participant will be asked to leave the room while the allocated treatment is prepared. Once ready for injection, vaccine and placebo will look similar, and the participant will not be able to tell the difference. The physicians administering the treatment are not blinded. Numbers to be randomised (sample size): Sample size: N=1,500. The 1,500 participants will be randomised 1:1 to BCG or placebo with 750 participants in each group. Trial Status: Current protocol version 5.1, from July 6, 2020. Recruitment of study participants started on May 18, 2020 and we anticipate having finished recruiting by the end of December 2020. Trial registration: The trial was registered with EudraCT on April 16, 2020, EudraCT number: 2020-001888-90, and with ClinicalTrials.gov on May 1, 2020, registration number NCT04373291. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Keywords: COVID-19, Randomised controlled trial, Protocol, BCG vaccine, NSEs/Non-specific effects of vaccines, Heterologous effects of vaccines, Health care workers, Pandemic, Immune training. The primary objective is to reduce absenteeism due to illness among HCW during the COVID-19 pandemic. The secondary objectives are to reduce the number of HCW that are infected with SARS-CoV-2, and to reduce the number of hospital admissions among HCW during the COVID-19 pandemic. To be eligible for participation, a subject must meet the following criteria: Adult ([greater than or equai to]18 years); Hospital personnel working at a participating hospital for more than 22 hours per week. Secondary study endpoints: The cumulative incidence of documented COVID-19 and the cumulative incidence of hospital admission for any reason within 180 days of randomisation. Abstract Objectives: The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and significant reductions in all-cause morbidity and mortality have been reported. We aim to test whether BCG vaccination may reduce susceptibility to and/or the severity of COVID-19 and other infectious diseases in health care workers (HCW) and thus prevent work absenteeism. The primary objective is to reduce absenteeism due to illness among HCW during the COVID-19 pandemic. The secondary objectives are to reduce the number of HCW that are infected with SARS-CoV-2, and to reduce the number of hospital admissions among HCW during the COVID-19 pandemic. Hypothesis: BCG vaccination of HCW will reduce absenteeism by 20% over a period of 6 months. Trial design: Placebo-controlled, single-blinded, randomised controlled trial, recruiting study participants at several geographic locations. The BCG vaccine is used in this study on a different indication than the one it has been approved for by the Danish Medicines Agency, therefore this is classified as a phase III study. Participants: The trial will recruit 1,500 HCW at Danish hospitals. To be eligible for participation, a subject must meet the following criteria: Adult (≥18 years); Hospital personnel working at a participating hospital for more than 22 hours per week. A potential subject who meets any of the following criteria will be excluded from participation in this study: Known allergy to components of the BCG vaccine or serious adverse events to prior BCG administration Known prior active or latent infection with Mycobacterium tuberculosis (M. tuberculosis) or other mycobacterial species Previous confirmed COVID-19 Fever (>38 C) within the past 24 hours Suspicion of active viral or bacterial infection Pregnancy Breastfeeding Vaccination with other live attenuated vaccine within the last 4 weeks Severely immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1) b) subjects with solid organ transplantation c) subjects with bone marrow transplantation d) subjects under chemotherapy e) subjects with primary immunodeficiency f) subjects under treatment with any anti-cytokine therapy within the last year g) subjects under treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months h) Active solid or non-solid malignancy or lymphoma within the prior two years Direct involvement in the design or the execution of the BCG-DENMARK-COVID trial Intervention and comparator: Participants will be randomised to BCG vaccine (BCG-Denmark, AJ Vaccines, Copenhagen, Denmark) or placebo (saline). An adult dose of 0.1 ml of resuspended BCG vaccine (intervention) or 0.1 ml of sterile 0.9% NaCl solution (control) is administered intradermally in the upper deltoid area of the right arm. All participants will receive one injection at inclusion, and no further treatment of study participants will take place. Main outcomes: Main study endpoint: Days of unplanned absenteeism due to illness within 180 days of randomisation. Secondary study endpoints: The cumulative incidence of documented COVID-19 and the cumulative incidence of hospital admission for any reason within 180 days of randomisation. Randomisation: Randomisation will be done centrally using the REDCap tool with stratification by hospital, sex and age groups (+/- 45 years of age) in random blocks of 4 and 6. The allocation ratio is 1:1. Blinding (masking): Participants will be blinded to treatment. The participant will be asked to leave the room while the allocated treatment is prepared. Once ready for injection, vaccine and placebo will look similar, and the participant will not be able to tell the difference. The physicians administering the treatment are not blinded. Numbers to be randomised (sample size): Sample size: N=1,500. The 1,500 participants will be randomised 1:1 to BCG or placebo with 750 participants in each group. Trial Status: Current protocol version 5.1, from July 6, 2020. Recruitment of study participants started on May 18, 2020 and we anticipate having finished recruiting by the end of December 2020. Trial registration: The trial was registered with EudraCT on April 16, 2020, EudraCT number: 2020-001888-90, and with ClinicalTrials.gov on May 1, 2020, registration number NCT04373291. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Keywords: COVID-19, Randomised controlled trial, Protocol, BCG vaccine, NSEs/Non-specific effects of vaccines, Heterologous effects of vaccines, Health care workers, Pandemic, Immune training. Objectives: The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and significant reductions in all-cause morbidity and mortality have been reported. We aim to test whether BCG vaccination may reduce susceptibility to and/or the severity of COVID-19 and other infectious diseases in health care workers (HCW) and thus prevent work absenteeism. The primary objective is to reduce absenteeism due to illness among HCW during the COVID-19 pandemic. The secondary objectives are to reduce the number of HCW that are infected with SARS-CoV-2, and to reduce the number of hospital admissions among HCW during the COVID-19 pandemic. Hypothesis: BCG vaccination of HCW will reduce absenteeism by 20% over a period of 6 months. Trial design: Placebo-controlled, single-blinded, randomised controlled trial, recruiting study participants at several geographic locations. The BCG vaccine is used in this study on a different indication than the one it has been approved for by the Danish Medicines Agency, therefore this is classified as a phase III study. Participants: The trial will recruit 1,500 HCW at Danish hospitals. To be eligible for participation, a subject must meet the following criteria: Adult (≥18 years); Hospital personnel working at a participating hospital for more than 22 hours per week. A potential subject who meets any of the following criteria will be excluded from participation in this study: Known allergy to components of the BCG vaccine or serious adverse events to prior BCG administration Known prior active or latent infection with Mycobacterium tuberculosis (M. tuberculosis) or other mycobacterial species Previous confirmed COVID-19 Fever (>38 C) within the past 24 hours Suspicion of active viral or bacterial infection Pregnancy Breastfeeding Vaccination with other live attenuated vaccine within the last 4 weeks Severely immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1) b) subjects with solid organ transplantation c) subjects with bone marrow transplantation d) subjects under chemotherapy e) subjects with primary immunodeficiency f) subjects under treatment with any anti-cytokine therapy within the last year g) subjects under treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months h) Active solid or non-solid malignancy or lymphoma within the prior two years Direct involvement in the design or the execution of the BCG-DENMARK-COVID trial Intervention and comparator: Participants will be randomised to BCG vaccine (BCG-Denmark, AJ Vaccines, Copenhagen, Denmark) or placebo (saline). An adult dose of 0.1 ml of resuspended BCG vaccine (intervention) or 0.1 ml of sterile 0.9% NaCl solution (control) is administered intradermally in the upper deltoid area of the right arm. All participants will receive one injection at inclusion, and no further treatment of study participants will take place. Main outcomes: Main study endpoint: Days of unplanned absenteeism due to illness within 180 days of randomisation. Secondary study endpoints: The cumulative incidence of documented COVID-19 and the cumulative incidence of hospital admission for any reason within 180 days of randomisation. Randomisation: Randomisation will be done centrally using the REDCap tool with stratification by hospital, sex and age groups (+/- 45 years of age) in random blocks of 4 and 6. The allocation ratio is 1:1. Blinding (masking): Participants will be blinded to treatment. The participant will be asked to leave the room while the allocated treatment is prepared. Once ready for injection, vaccine and placebo will look similar, and the participant will not be able to tell the difference. The physicians administering the treatment are not blinded. Numbers to be randomised (sample size): Sample size: N=1,500. The 1,500 participants will be randomised 1:1 to BCG or placebo with 750 participants in each group. Trial Status: Current protocol version 5.1, from July 6, 2020. Recruitment of study participants started on May 18, 2020 and we anticipate having finished recruiting by the end of December 2020. Trial registration: The trial was registered with EudraCT on April 16, 2020, EudraCT number: 2020-001888-90, and with ClinicalTrials.gov on May 1, 2020, registration number NCT04373291. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Keywords: COVID-19, Randomised controlled trial, Protocol, BCG vaccine, NSEs/Non-specific effects of vaccines, Heterologous effects of vaccines, Health care workers, Pandemic, Immune training. Objectives: The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and significant reductions in all-cause morbidity and mortality have been reported. We aim to test whether BCG vaccination may reduce susceptibility to and/or the severity of COVID-19 and other infectious diseases in health care workers (HCW) and thus prevent work absenteeism.The primary objective is to reduce absenteeism due to illness among HCW during the COVID-19 pandemic. The secondary objectives are to reduce the number of HCW that are infected with SARS-CoV-2, and to reduce the number of hospital admissions among HCW during the COVID-19 pandemic.Hypothesis: BCG vaccination of HCW will reduce absenteeism by 20% over a period of 6 months.Trial design: Placebo-controlled, single-blinded, randomised controlled trial, recruiting study participants at several geographic locations. The BCG vaccine is used in this study on a different indication than the one it has been approved for by the Danish Medicines Agency, therefore this is classified as a phase III study.Participants: The trial will recruit 1,500 HCW at Danish hospitals.To be eligible for participation, a subject must meet the following criteria: Adult (≥18 years); Hospital personnel working at a participating hospital for more than 22 hours per week.A potential subject who meets any of the following criteria will be excluded from participation in this study: Known allergy to components of the BCG vaccine or serious adverse events to prior BCG administrationKnown prior active or latent infection with Mycobacterium tuberculosis (M. tuberculosis)or other mycobacterial speciesPrevious confirmed COVID-19Fever (>38 C) within the past 24 hoursSuspicion of active viral or bacterial infectionPregnancyBreastfeedingVaccination with other live attenuated vaccine within the last 4 weeksSeverely immunocompromised subjects. This exclusion category comprises:a) subjects with known infection by the human immunodeficiency virus (HIV-1)b) subjects with solid organ transplantationc) subjects with bone marrow transplantationd) subjects under chemotherapye) subjects with primary immunodeficiencyf) subjects under treatment with any anti-cytokine therapy within the last yearg) subjects under treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 monthsh) Active solid or non-solid malignancy or lymphoma within the prior two yearsDirect involvement in the design or the execution of the BCG-DENMARK-COVID trialIntervention and comparator: Participants will be randomised to BCG vaccine (BCG-Denmark, AJ Vaccines, Copenhagen, Denmark) or placebo (saline). An adult dose of 0.1 ml of resuspended BCG vaccine (intervention) or 0.1 ml of sterile 0.9% NaCl solution (control) is administered intradermally in the upper deltoid area of the right arm. All participants will receive one injection at inclusion, and no further treatment of study participants will take place.Main outcomes: Main study endpoint: Days of unplanned absenteeism due to illness within 180 days of randomisation.Secondary study endpoints: The cumulative incidence of documented COVID-19 and the cumulative incidence of hospital admission for any reason within 180 days of randomisation.Randomisation: Randomisation will be done centrally using the REDCap tool with stratification by hospital, sex and age groups (+/- 45 years of age) in random blocks of 4 and 6. The allocation ratio is 1:1.Blinding (masking): Participants will be blinded to treatment. The participant will be asked to leave the room while the allocated treatment is prepared. Once ready for injection, vaccine and placebo will look similar, and the participant will not be able to tell the difference.The physicians administering the treatment are not blinded.Numbers to be randomised (sample size): Sample size: N=1,500. The 1,500 participants will be randomised 1:1 to BCG or placebo with 750 participants in each group.Trial Status: Current protocol version 5.1, from July 6, 2020.Recruitment of study participants started on May 18, 2020 and we anticipate having finished recruiting by the end of December 2020.Trial registration: The trial was registered with EudraCT on April 16, 2020, EudraCT number: 2020-001888-90, and with ClinicalTrials.gov on May 1, 2020, registration number NCT04373291.Full protocol: The full protocol is attached as an additional file, accessible from the Trialswebsite (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.Keywords: COVID-19, Randomised controlled trial, Protocol, BCG vaccine, NSEs/Non-specific effects of vaccines, Heterologous effects of vaccines, Health care workers, Pandemic, Immune training. |
| ArticleNumber | 799 |
| Audience | Academic |
| Author | Bjerregaard-Andersen, Morten Netea, Mihai G Oedegaard, Emilie Sundhaugen Mohamed, Libin Krause, Tyra Grove Kristensen, Gitte Schultz Ditlev, Sisse Bolm Johansen, Isik Somuncu Aaby, Peter Nielsen, Sebastian Dam, Christine Loekkegaard, Ellen Christine Leth Dalgaard, Lars Skov Ostenfeld, Anne Schaltz-Buchholzer, Frederik Madsen, Anne Marie Rosendahl Jensen, Aksel Karl Georg Kofoed, Poul-Erik Faizi, Gulia Mogensen, Christian Backer Soerensen, Marcus Kjaer Benfield, Thomas Wejse, Christian Benn, Christine Stabell |
| Author_xml | – sequence: 1 givenname: Anne Marie Rosendahl orcidid: 0000-0002-3396-3554 surname: Madsen fullname: Madsen, Anne Marie Rosendahl email: arosendahl@health.sdu.dk organization: Bandim Health Project, OPEN, Department of Clinical Research, University of Southern Denmark/Odense University Hospital, Odense, Denmark. arosendahl@health.sdu.dk – sequence: 2 givenname: Frederik surname: Schaltz-Buchholzer fullname: Schaltz-Buchholzer, Frederik organization: Bandim Health Project, OPEN, Department of Clinical Research, University of Southern Denmark/Odense University Hospital, Odense, Denmark – sequence: 3 givenname: Thomas surname: Benfield fullname: Benfield, Thomas organization: Center of Research & Disruption of Infectious Diseases (CREDID), Department of Infectious Diseases, Copenhagen University Hospital, Amager and Hvidovre Hospital, Hvidovre, Denmark – sequence: 4 givenname: Morten surname: Bjerregaard-Andersen fullname: Bjerregaard-Andersen, Morten organization: Department of Medicine, Sydvestjysk Hospital, Esbjerg, Denmark – sequence: 5 givenname: Lars Skov surname: Dalgaard fullname: Dalgaard, Lars Skov organization: Department of Medicine, Herning Hospital, Herning, Denmark – sequence: 6 givenname: Christine surname: Dam fullname: Dam, Christine organization: Department of Respiratory Medicine, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark – sequence: 7 givenname: Sisse Bolm surname: Ditlev fullname: Ditlev, Sisse Bolm organization: The Copenhagen Center for Translational Research (CCTR), Bispebjerg Hospital, Copenhagen, Denmark – sequence: 8 givenname: Gulia surname: Faizi fullname: Faizi, Gulia organization: Department of Medicine, Sydvestjysk Hospital, Esbjerg, Denmark – sequence: 9 givenname: Isik Somuncu surname: Johansen fullname: Johansen, Isik Somuncu organization: Department of Infectious Diseases, Odense University Hospital, Odense, Denmark – sequence: 10 givenname: Poul-Erik surname: Kofoed fullname: Kofoed, Poul-Erik organization: Department of Pediatrics, Lillebaelt Hospital, Kolding, Denmark – sequence: 11 givenname: Gitte Schultz surname: Kristensen fullname: Kristensen, Gitte Schultz organization: Department of Medicine, Soenderjylland Hospital, Aabenraa, Denmark – sequence: 12 givenname: Ellen Christine Leth surname: Loekkegaard fullname: Loekkegaard, Ellen Christine Leth organization: Department of Gynaecology and Obstetrics, Nordsjaellands Hospital, Hilleroed, Denmark – sequence: 13 givenname: Christian Backer surname: Mogensen fullname: Mogensen, Christian Backer organization: Department of Medicine, Soenderjylland Hospital, Aabenraa, Denmark – sequence: 14 givenname: Libin surname: Mohamed fullname: Mohamed, Libin organization: Department of Pediatrics, Lillebaelt Hospital, Kolding, Denmark – sequence: 15 givenname: Anne surname: Ostenfeld fullname: Ostenfeld, Anne organization: Department of Gynaecology and Obstetrics, Nordsjaellands Hospital, Hilleroed, Denmark – sequence: 16 givenname: Emilie Sundhaugen surname: Oedegaard fullname: Oedegaard, Emilie Sundhaugen organization: Bandim Health Project, OPEN, Department of Clinical Research, University of Southern Denmark/Odense University Hospital, Odense, Denmark – sequence: 17 givenname: Marcus Kjaer surname: Soerensen fullname: Soerensen, Marcus Kjaer organization: Bandim Health Project, OPEN, Department of Clinical Research, University of Southern Denmark/Odense University Hospital, Odense, Denmark – sequence: 18 givenname: Christian surname: Wejse fullname: Wejse, Christian organization: Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark – sequence: 19 givenname: Aksel Karl Georg surname: Jensen fullname: Jensen, Aksel Karl Georg organization: Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark – sequence: 20 givenname: Sebastian surname: Nielsen fullname: Nielsen, Sebastian organization: Bandim Health Project, OPEN, Department of Clinical Research, University of Southern Denmark/Odense University Hospital, Odense, Denmark – sequence: 21 givenname: Tyra Grove surname: Krause fullname: Krause, Tyra Grove organization: Statens Serum Institut, Copenhagen, Denmark – sequence: 22 givenname: Mihai G surname: Netea fullname: Netea, Mihai G organization: Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany – sequence: 23 givenname: Peter surname: Aaby fullname: Aaby, Peter organization: Bandim Health Project, OPEN, Department of Clinical Research, University of Southern Denmark/Odense University Hospital, Odense, Denmark – sequence: 24 givenname: Christine Stabell surname: Benn fullname: Benn, Christine Stabell organization: Bandim Health Project, OPEN, Department of Clinical Research, University of Southern Denmark/Odense University Hospital, Odense, Denmark |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32943115$$D View this record in MEDLINE/PubMed |
| BookMark | eNptks1u1DAUhSNURH_gBVggS6xT_BfHZoFUplBGqtQNZWvdOM6Mpxl7sJ2iPh2vhmemlI6EsrBzcs-Xe-1zWh354G1VvSX4nBApPiTCsGA1prjGvCW8Zi-qE9LyphaUNEfP9sfVaUorjDlTjL-qjhlVnBHSnFS_b5PzC_R5doXuwRjnLcoBWb8EbywqP6zTxho3OIM2MWRrsgsehQEtLYx5iQxEi36FeGdjQv0Ut7C8tGh282N-WROFNuB7u3bmI7pAKcfJ5CnaHqVpvYb4sCVB0af-YccPJoxoCLGIsRjD2qVSbILPMYxj2eboYETOo0vrC-DudfVygDHZN4_rWXX79cv32bf6-uZqPru4rk0jWK4lpqprjVKd6Bo-AFHE9KyTtGFUKsLbrlG97BRgCYOkhEoQQHDbCcNFEdlZNd9z-wArvYlu270O4PROCHGhIWZnRquJsEoC9AAWODcEMChMgXSqb8tbU1if9qzN1K1tb2yZDsYD6OEX75Z6Ee51y1XDMS2A94-AGH5ONmW9ClP0ZX5NJaGMlPvF_6oWULpyfggFZsqJGn0hmJBCsWbLOv9PVXl2t1YCN7iiHxjo3mBiSCna4alxgvU2l3qfS11yqXe51KyY3j0f-cnyN4jsD9IM4VQ |
| CitedBy_id | crossref_primary_10_1016_j_vaccine_2024_02_049 crossref_primary_10_3390_vaccines10101641 crossref_primary_10_1016_j_ijid_2021_07_041 crossref_primary_10_1016_j_it_2021_12_001 crossref_primary_10_54044_RAMI_2021_01_07 crossref_primary_10_1016_j_isci_2023_106873 crossref_primary_10_3390_jcm11030526 crossref_primary_10_1128_mbio_00356_23 crossref_primary_10_3389_fimmu_2021_612747 crossref_primary_10_1016_j_vaccine_2021_03_092 crossref_primary_10_1016_j_vaccine_2022_06_039 crossref_primary_10_1093_infdis_jiad422 crossref_primary_10_3389_fimmu_2022_873067 crossref_primary_10_1371_journal_pone_0258743 crossref_primary_10_3389_fpsyg_2021_621853 crossref_primary_10_1002_JLB_4A0720_458RR crossref_primary_10_1016_j_vaccine_2021_06_006 crossref_primary_10_12998_wjcc_v9_i19_5007 crossref_primary_10_2147_IJGM_S393861 crossref_primary_10_1186_s12879_021_06949_0 crossref_primary_10_1186_s43168_021_00052_3 crossref_primary_10_1016_j_intimp_2021_108232 crossref_primary_10_1155_2022_2759513 |
| ContentType | Journal Article |
| Copyright | COPYRIGHT 2020 BioMed Central Ltd. The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. The Author(s) 2020 |
| Copyright_xml | – notice: COPYRIGHT 2020 BioMed Central Ltd. – notice: The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: The Author(s) 2020 |
| DBID | CGR CUY CVF ECM EIF NPM AAYXX CITATION 3V. 7RV 7X7 7XB 88E 8FI 8FJ 8FK ABUWG AFKRA AZQEC BENPR CCPQU COVID DWQXO FYUFA GHDGH K9. KB0 M0S M1P NAPCQ PIMPY PQEST PQQKQ PQUKI PRINS 5PM DOA |
| DOI | 10.1186/s13063-020-04714-3 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed CrossRef ProQuest Central (Corporate) Proquest Nursing & Allied Health Source ProQuest Health & Medical Collection ProQuest Central (purchase pre-March 2016) Medical Database (Alumni Edition) Hospital Premium Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) ProQuest Central (Alumni) ProQuest Central ProQuest Central Essentials ProQuest Central ProQuest One Community College Coronavirus Research Database ProQuest Central Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Health & Medical Complete (Alumni) Nursing & Allied Health Database (Alumni Edition) Health & Medical Collection (Alumni Edition) PML(ProQuest Medical Library) Nursing & Allied Health Premium Publicly Available Content Database ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Academic ProQuest One Academic UKI Edition ProQuest Central China PubMed Central (Full Participant titles) Directory of Open Access Journals |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) CrossRef Publicly Available Content Database ProQuest Central Essentials ProQuest One Academic Eastern Edition ProQuest Health & Medical Complete (Alumni) Coronavirus Research Database ProQuest Central (Alumni Edition) ProQuest One Community College ProQuest Nursing & Allied Health Source ProQuest Hospital Collection Health Research Premium Collection (Alumni) ProQuest Central China ProQuest Hospital Collection (Alumni) ProQuest Central Nursing & Allied Health Premium ProQuest Health & Medical Complete Health Research Premium Collection ProQuest Medical Library ProQuest One Academic UKI Edition Health and Medicine Complete (Alumni Edition) ProQuest Central Korea ProQuest Nursing & Allied Health Source (Alumni) ProQuest One Academic ProQuest Medical Library (Alumni) ProQuest Central (Alumni) |
| DatabaseTitleList | MEDLINE CrossRef Publicly Available Content Database |
| Database_xml | – sequence: 1 dbid: DOA name: Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database – sequence: 4 dbid: BENPR name: ProQuest Central url: https://www.proquest.com/central sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1745-6215 |
| EndPage | 3 |
| ExternalDocumentID | oai_doaj_org_article_16e98aadaaea44c1a0a902a1b9d7c1a5 A636869352 10_1186_s13063_020_04714_3 32943115 |
| Genre | Clinical Trial Protocol Letter Correspondence |
| GeographicLocations | Denmark Germany |
| GeographicLocations_xml | – name: Denmark – name: Germany |
| GrantInformation_xml | – fundername: ; |
| GroupedDBID | --- -5E -5G -A0 -BR 0R~ 123 2-G 29Q 2WC 53G 5VS 6PF 7RV 7X7 88E 8FI 8FJ AAFWJ AAJSJ AAWTL ABDBF ABUWG ACGFO ACGFS ACRMQ ADBBV ADINQ ADRAZ ADUKV AEGXH AENEX AFKRA AFPKN AHBYD AHYZX AIAGR ALIPV ALMA_UNASSIGNED_HOLDINGS AMKLP AMTXH AOIJS BAPOH BAWUL BCNDV BENPR BFQNJ BMC C24 C6C CCPQU CGR CS3 CUY CVF DIK DU5 E3Z EBD EBLON EBS ECM EIF EMOBN ESX F5P FYUFA GROUPED_DOAJ GX1 HMCUK HYE IAO IHR INH INR ITC KQ8 M1P M48 M~E NAPCQ NPM O5R O5S PGMZT PIMPY PSQYO RBZ RNS ROL RPM RSV SMD SOJ SV3 TR2 TUS U2A UKHRP WOQ WOW ~8M AAYXX CITATION ABVAZ AFGXO AFNRJ 3V. 5GY 7XB 8FK AHMBA AZQEC COVID DWQXO FRP K9. PQEST PQQKQ PQUKI PRINS XSB 5PM |
| ID | FETCH-LOGICAL-c563t-8029b7c99b6b54fa191cd3b8253289147b59d8b9a08af82128a6a107b6c46a083 |
| IEDL.DBID | RPM |
| ISSN | 1745-6215 |
| IngestDate | Tue Oct 22 15:14:16 EDT 2024 Tue Sep 17 21:22:00 EDT 2024 Thu Oct 10 18:42:32 EDT 2024 Thu Feb 22 23:46:30 EST 2024 Tue Nov 12 23:33:31 EST 2024 Thu Sep 12 16:46:11 EDT 2024 Sat Sep 28 08:26:42 EDT 2024 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 1 |
| Keywords | COVID-19 Heterologous effects of vaccines Randomised controlled trial Health care workers NSEs/Non-specific effects of vaccines Pandemic Immune training Protocol BCG vaccine |
| Language | English |
| License | Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c563t-8029b7c99b6b54fa191cd3b8253289147b59d8b9a08af82128a6a107b6c46a083 |
| ORCID | 0000-0002-3396-3554 |
| OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495402/ |
| PMID | 32943115 |
| PQID | 2812313290 |
| PQPubID | 44365 |
| PageCount | 3 |
| ParticipantIDs | doaj_primary_oai_doaj_org_article_16e98aadaaea44c1a0a902a1b9d7c1a5 pubmedcentral_primary_oai_pubmedcentral_nih_gov_7495402 proquest_journals_2812313290 gale_infotracmisc_A636869352 gale_infotracacademiconefile_A636869352 crossref_primary_10_1186_s13063_020_04714_3 pubmed_primary_32943115 |
| PublicationCentury | 2000 |
| PublicationDate | 2020-09-17 |
| PublicationDateYYYYMMDD | 2020-09-17 |
| PublicationDate_xml | – month: 09 year: 2020 text: 2020-09-17 day: 17 |
| PublicationDecade | 2020 |
| PublicationPlace | England |
| PublicationPlace_xml | – name: England – name: London |
| PublicationTitle | Current controlled trials in cardiovascular medicine |
| PublicationTitleAlternate | Trials |
| PublicationYear | 2020 |
| Publisher | BioMed Central Ltd BioMed Central BMC |
| Publisher_xml | – name: BioMed Central Ltd – name: BioMed Central – name: BMC |
| SSID | ssj0043934 ssj0017864 |
| Score | 2.4078 |
| Snippet | The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and significant... Abstract Objectives: The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other... Objectives: The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and... The primary objective is to reduce absenteeism due to illness among HCW during the COVID-19 pandemic. The secondary objectives are to reduce the number of HCW... Objectives: The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and... Abstract Objectives: The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other... |
| SourceID | doaj pubmedcentral proquest gale crossref pubmed |
| SourceType | Open Website Open Access Repository Aggregation Database Index Database |
| StartPage | 799 |
| SubjectTerms | Absenteeism Bacterial infections BCG BCG Vaccine - administration & dosage BCG Vaccine - adverse effects Betacoronavirus - immunology Betacoronavirus - pathogenicity Coronavirus Infections - immunology Coronavirus Infections - prevention & control Coronavirus Infections - transmission Coronavirus Infections - virology Coronaviruses COVID-19 COVID-19 vaccines Denmark Female Health aspects Health Personnel Humans Immune system Infections Letter Male Medical personnel Multicenter Studies as Topic Occupational Health Pandemics Pandemics - prevention & control Patient Admission Pneumonia, Viral - immunology Pneumonia, Viral - prevention & control Pneumonia, Viral - transmission Pneumonia, Viral - virology Prevention Randomized Controlled Trials as Topic Risk factors SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Sick Leave Single-Blind Method Testing Time Factors Treatment Outcome Tuberculosis Vaccination |
| SummonAdditionalLinks | – databaseName: Directory of Open Access Journals dbid: DOA link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1LbxMxELZQD4gL4s1CQXNA4oCsrtdeP7ilKaUgFS4U9WbZXq8aFTYVDfw9_hrjR6qsOHDhlsw6ltfz2TMTz3wm5JVkwQ9966jXfKRCjoEa02k6RK5CNMGEnPJ_-kmenImP5_35zlVfKSes0AOXiTtgMhrt3OBcdEIE5lpn2s4xbwaF3wp7aWu2wVTZg9HKcrEtkdHy4Bp36nxemVIZFROUz8xQZuv_e0_eMUrzhMkdC3R8j9ytriMsypDvk1txekBun9bD8Yfkdz7-h8Ple_jlQpLBZg1xukiKBQzzaSqrTKlBUNkZUCewHqHUQkJKAoOUp4UeIZTyRUD3EJafv344oszAVfrD-fsqvIUFFN7Znz_iALX-LfXkINPV5v7XCDFAlxiFaA-HNQIKG9fU-G_4MV8YAqsJjuKEHVw-ImfH774sT2i9n4GGXvINGrfOeBWM8dL3YnQY-oWBe4w5OYZxTCjfm0F741rtRo02UjvpMNz0MgiJQv6Y7OHLx6cEQoebQ3D4k1GJ3st0JRA6L6NXzISxUw15s1WXvSo0HDaHL1raolyLyrVZuZY35DBp9KZlotDOAgSWrcCy_wJWQ14nPNi00FHpwdV6BRxwosyyC8mllgYd2Ibsz1rifIb54y2ibN0grm2HjlVizTRtQ54UcN0MF6UikSA1RM1gN3uf-ZNpdZGpwRXGu6Ltnv2PCXhO7nR5xRjK1D7ZQ1zFF-iBbfzLvNj-AHybMNk priority: 102 providerName: Directory of Open Access Journals – databaseName: ProQuest Central dbid: BENPR link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1LbxMxELYglRCXijcLBc0BiQOyug-vH1xQkrYUpBaEKOrNsr1eGkF3QxP4e_w1xl4ndIXELZl1vLuZ8TzsmW8IecELZ5s6N9TKqqWMt44qVUra-Eo4r5xyMeX_5JQfn7H35_V52nBbpbTKjU6MirrpXdgj3y_REgWYQZW_Wf6goWtUOF1NLTRukp0SI4V8QnZmh6cfP23PEYTkbFMqI_n-CjV2PLcMKY2iYLQamaOI2v-vbr5mnMaJk9cs0dEdsptcSJgOPL9LbvjuHrl1kg7J75PfMQ0AZvO38Mu4QIN1D767CAwGDPdpKK8MKUKQUBqQN9C3MNREQkgGg5CvhZ4hDGWMgG4izD98eXdACwXLsPF8uXCvYQoD_uzPK99AqoMLMxmIsLVx_h5FDdA1RiLaxaZHwcLBKUX-O36MjUNg0cGB73CCbw_I2dHh5_kxTX0aqKt5tUYjVyornFKW25q1BkNA11QWY88Kw7mCCVurRlplcmlaibZSGm4w7LTcMY7E6iGZ4Mv7xwRciUrCGfxJK1hteWgNhE5Ma0WhXFuKjLzasEsvBzgOHcMYyfXAXI3M1ZG5usrILHB0OzJAaUdCf_VVp5WpC-6VNKYxxhvGXGFyo_LSFFY1Ar_VGXkZ5EGHBY9MdybVLeADB-gsPeUVl1yhI5uRvdFI_D_d-PJGonRSFCv9V6wz8mgQru3jIpUFMKSMiJHYjd5nfKVbXESIcIFxL8vLJ_-_5VNyu4xrQdFC7JEJSox_hj7W2j5PC-kPqQAoPg priority: 102 providerName: ProQuest – databaseName: Scholars Portal Open Access Journals dbid: M48 link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Lb9QwELZKkRAXxJtAQXNA4oAMSez4gYTQdkspSIULi3qzbMdpV5SkbBcEv46_xthJVo3okdvuxLESzzeemXgehDwVhXd1lVvqFGsoF42nWpeK1oFJH7TXPoX8H34UBwv-4ag62iJju6NhAc8vde1iP6nF6vTFr--_36DAv04Cr8TLc9yH02lkDFSUBafsCrlacvTUYygf35wqoO5lfEycufS-iXJKNfz_3akvqKppGOUFvbR_k9wYDEqY9Qi4RbZCe5tcOxyOzO-QPykoAHbn7-Cn9ZEG6w5CexLZDej805hsGQOGYKjZgJyCroE-QxJiaBjE6C20E6FPagQ0GmH-6cv7PVpoOIufob8t_SuYQV-N9scq1DBkxcWZLKQitmn-DoEHaCgjEbVk3SHMcPAQMH-KP1MbEVi2sBdanODrXbLYf_t5fkCHrg3UV4KtUeWV2kmvtROu4o1Fh9DXzKEnytC5K7h0la6V0zZXtlGoOZUVFp1QJzwXSGT3yDa-fHhAwJe4ZXiLtzSSV07ERkFo0jROFto3pczI85Fd5qwvzmGSU6OE6ZlrkLkmMdewjOxGjm5GxsLaidCtjs0gp6YQQStra2uD5dwXNrc6L23hdC3xX5WRZxEPJgISme7tkMWADxwLaZmZYEIJjWZtRnYmI3E9_fTyiCgzot6UaG7FWpo6z8j9Hlybx0Uqj6WRMiInsJu8z_RKuzxJBcMlesE8Lx_-jwV4RK6XSWI0LeQO2UZchcdol63dkyRsfwFl3jfH priority: 102 providerName: Scholars Portal |
| Title | Using BCG vaccine to enhance non-specific protection of health care workers during the COVID-19 pandemic: A structured summary of a study protocol for a randomised controlled trial in Denmark |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/32943115 https://www.proquest.com/docview/2812313290 https://pubmed.ncbi.nlm.nih.gov/PMC7495402 https://doaj.org/article/16e98aadaaea44c1a0a902a1b9d7c1a5 |
| Volume | 21 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwELbaIiEuiHcDZTUHJA4o3U3s-MEtu32x0pYKKNqbZTsJXdFNVu3C3-OvMXaSqhE3LsnGSSxn5xvPTPLNmJB3PHG2yCYmtpJWMeOVi5VKZVyUVLhSOeUC5X9xzs8u2XyZLXdI1ufCBNK-s6vD-np9WK-uArdys3bjnic2vljMBHr1GPeMd8kuArQP0dvpFw0sZX12jOTjW5ykw6dKz2IUCYv9yjk0VcyXmRkYo1Cz_9-Z-Z5pGtIm79mhkyfkcedAQt4O9CnZKetn5OGi-0T-nPwJJACYzk7ht3G-DbYNlPWVFy9gsB_75EpPEIKuRgNKBpoK2oxI8FQw8Gwt9AuhTWIEdBJh9vn7p6M4UbDxr53XK_cRcmirz_66KQvosuB8TwZC0drQf4NAA3SMsRGtYtEgrPDijiB_jT_DsiGwquGorLGDny_I5cnxt9lZ3K3SELuM0y2auFRZ4ZSy3GasMhgAuoJajDwpBnMJEzZThbTKTKSpJFpKabjBoNNyxzg20pdkDx--3CfgUpwinMFbKsEyy_3CQOjCVFYkylWpiMiHXlx60xbj0CGIkVy3ctYoZx3krGlEpl6id1f6Qtqhobn5oTs46YSXShpTGFMaxlxiJkZNUpNYVQg8yiLy3uNBe3VHoTvTZS3ggH3hLJ1zyiVX6MZG5GBwJf6fbni6R5TupolbnaJ75WtnqklEXrXguhtuj9GIiAHsBs8zPIP6EgqEd_rx-r_vfEMepUFjVJyIA7KHYCrfovO1tSNUuaUYkQd5Pv86x_30-PziC-4DCkfhlQZuT5cJbhdMjoJy_gW0UzhJ |
| link.rule.ids | 230,315,730,783,787,867,888,2109,12068,21400,24330,27936,27937,31731,33756,38528,43322,43817,43907,53804,53806,74073,74630,74740 |
| linkProvider | National Library of Medicine |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lc9MwENZAOwNceD8MBfbADAdGrR-yHlyYNKWk0JZLy_SmkWSbZgp2aFIO_Dn-GitZCTXMcOCWrBXZcj7tQ9r9RMgLnjlblamhVhYNZbxxVKlc0qouhKuVUy6k_B8c8skxe39SnsQFt3lMq1zqxKCoq875NfKtHC2RpxlU6ZvZN-pPjfK7q_EIjatkHQ1risHX-vjjp72d1T6CkJwtS2Uk35qjxg77lj6lUWSMFgNzFFj7_9bNl4zTMHHykiXavUX0cgx9AsrZ5sXCbroff9A7_v8gb5Ob0UmFUY-qO-RK3d4l1w7iNvw98jMkGsD2-B18N87LYNFB3Z56CEHbtdQXcPokJIg8EPjvQ9dAX3UJPt0MfEYY-p7QF0oCOqIQ3irNFMz80vbXqXsNI-gZbi_O6wpipZ3vyUAgxg39dwhmQOcbhWh5qw6hi41jEv4X_BiOJoFpCzt1ix2c3SfHu2-PxhMaT4KgruTFAs1orqxwSlluS9YYDDJdVViMbgsMGDMmbKkqaZVJpWkkWmNpuMHA1nLHOAqLB2QNB18_IuByVEPO4E8awUrL_eFD6CY1VmTKNblIyKslIPSsJ_zQIVCSXPfw0QgfHeCji4Rse8ysWnqy7iDozj_rOPd1xmsljamMqQ1jLjOpUWluMqsqgd_KhLz0iNNepSCsnImVEfjAnpxLj3jBJVfoKidkY9AS36cbXl7CSkdVNNe_MZWQhz18V4-LUubplhIiBsAejGd4pZ2eBhJygZE1S_PH_77lc3J9cnSwr_f3Dj88ITfyMPMUzcQGWUP01E_Ro1vYZ3Ha_gIV4E4P |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Nb9MwGLagkyYufDMCA94DEgeUNR-OP7igrqVswAYHhnazbCdhVSEpa8eBP8df47XjlgUkTtxSx3Hj6Mn7ET_vY0KestSaskh0bERex5TVNpYyE3FZ5dxW0krrKf9Hx-zghL45LU4D_2kZaJVrm-gNddla9418mKEncjKDMhnWgRbxYTJ9ufgWux2k3Epr2E7jKtnCEJkmA7I1fv_pcLJZU-CC0XXZjGDDJVpvv4bp6I08pXHec01ewf9vO33JUfVJlJe80vQGma_n05FR5nsXK7Nnf_wh9fh_JnyTXA_BK4w6tN0iV6rmNtk-Csvzd8hPT0CA_fFr-K6ta4NVC1Vz5qAFTdvErrDTkZMg6EMgKqCtoavGBEdDA8cUw5gUugJKwAAV_BOOUwkL98n768y-gBF0yrcX51UJoQLPjaTBC-b68VsEOWBQjo3okcsWIY2dAzn_Cx76LUtg1sCkanCA-V1yMn31cXwQhx0iYluwfIXuNZOGWykNMwWtNSaftswNZr05JpIp5aaQpTBSJ0LXAr200ExjwmuYpQwb83tkgJOv7hOwGZonq_GSmtPCMLcpEYZPteGptHXGI_J8DQ616IRAlE-gBFMdlBRCSXkoqTwi-w4_m55OxNs3tOefVbAJKmWVFFqXWleaUpvqRMsk06mRJcdfRUSeOfQpZ2oQYlaHigm8YSfapUYsZ4JJDKEjstvric_T9k-vIaaCiVqq3_iKyE4H5c3tYit1MkwR4T2Q9-bTP9PMzrw4OceMmybZg3__5ROyjWBW7w6P3z4k1zL_Eso45btkgOCpHmGgtzKPwxv8C9HzVsw |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Using+BCG+vaccine+to+enhance+non-specific+protection+of+health+care+workers+during+the+COVID-19+pandemic%3A+A+structured+summary+of+a+study+protocol+for+a+randomised+controlled+trial+in+Denmark&rft.jtitle=Trials&rft.au=Anne+Marie+Rosendahl+Madsen&rft.au=Frederik+Schaltz-Buchholzer&rft.au=Thomas+Benfield&rft.au=Morten+Bjerregaard-Andersen&rft.date=2020-09-17&rft.pub=BMC&rft.eissn=1745-6215&rft.volume=21&rft.issue=1&rft.spage=1&rft.epage=3&rft_id=info:doi/10.1186%2Fs13063-020-04714-3&rft.externalDBID=DOA&rft.externalDocID=oai_doaj_org_article_16e98aadaaea44c1a0a902a1b9d7c1a5 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1745-6215&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1745-6215&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1745-6215&client=summon |