TY - JOUR
T1 - Efficacy of BCG Vaccination Against Respiratory Tract Infections in Older Adults During the Coronavirus Disease 2019 Pandemic
AU - Moorlag, Simone J C F M
AU - Taks, Esther
AU - Ten Doesschate, Thijs
AU - van der Vaart, Thomas W
AU - Janssen, Axel B
AU - Müller, Lisa
AU - Ostermann, Philipp
AU - Dijkstra, Helga
AU - Lemmers, Heidi
AU - Simonetti, Elles
AU - Mazur, Marc
AU - Schaal, Heiner
AU - Ter Heine, Rob
AU - van de Veerdonk, Frank L
AU - Bleeker-Rovers, Chantal P
AU - van Crevel, Reinout
AU - Ten Oever, Jaap
AU - de Jonge, Marien I
AU - Bonten, Marc J
AU - van Werkhoven, Cornelis H
AU - Netea, Mihai G
N1 - Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America.
PY - 2022/7/1
Y1 - 2022/7/1
N2 - BACKGROUND: Older age is associated with increased severity and death from respiratory infections, including coronavirus disease 2019 (COVID-19). The tuberculosis BCG vaccine may provide heterologous protection against nontuberculous infections and has been proposed as a potential preventive strategy against COVID-19.METHODS: In this multicenter, placebo-controlled trial, we randomly assigned older adults (aged ≥60 years; n = 2014) to intracutaneous vaccination with BCG vaccine (n = 1008) or placebo (n = 1006). The primary end point was the cumulative incidence of respiratory tract infections (RTIs) that required medical intervention, during 12 months of follow-up. Secondary end points included the incidence of COVID-19, and the effect of BCG vaccination on the cellular and humoral immune responses.RESULTS: The cumulative incidence of RTIs requiring medical intervention was 0.029 in the BCG-vaccinated group and 0.024 in the control group (subdistribution hazard ratio, 1.26 [98.2% confidence interval, .65-2.44]). In the BCG vaccine and placebo groups, 51 and 48 individuals, respectively tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with polymerase chain reaction (subdistribution hazard ratio, 1.053 [95% confidence interval, .71-1.56]). No difference was observed in the frequency of adverse events. BCG vaccination was associated with enhanced cytokine responses after influenza, and also partially associated after SARS-CoV-2 stimulation. In patients diagnosed with COVID-19, antibody responses after infection were significantly stronger if the volunteers had previously received BCG vaccine.CONCLUSIONS: BCG vaccination had no effect on the incidence of RTIs, including SARS-CoV-2 infection, in older adult volunteers. However, it improved cytokine responses stimulated by influenza and SARS-CoV-2 and induced stronger antibody titers after COVID-19 infection.CLINICAL TRIALS REGISTRATION: EU Clinical Trials Register 2020-001591-15 ClinicalTrials.gov NCT04417335.
AB - BACKGROUND: Older age is associated with increased severity and death from respiratory infections, including coronavirus disease 2019 (COVID-19). The tuberculosis BCG vaccine may provide heterologous protection against nontuberculous infections and has been proposed as a potential preventive strategy against COVID-19.METHODS: In this multicenter, placebo-controlled trial, we randomly assigned older adults (aged ≥60 years; n = 2014) to intracutaneous vaccination with BCG vaccine (n = 1008) or placebo (n = 1006). The primary end point was the cumulative incidence of respiratory tract infections (RTIs) that required medical intervention, during 12 months of follow-up. Secondary end points included the incidence of COVID-19, and the effect of BCG vaccination on the cellular and humoral immune responses.RESULTS: The cumulative incidence of RTIs requiring medical intervention was 0.029 in the BCG-vaccinated group and 0.024 in the control group (subdistribution hazard ratio, 1.26 [98.2% confidence interval, .65-2.44]). In the BCG vaccine and placebo groups, 51 and 48 individuals, respectively tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with polymerase chain reaction (subdistribution hazard ratio, 1.053 [95% confidence interval, .71-1.56]). No difference was observed in the frequency of adverse events. BCG vaccination was associated with enhanced cytokine responses after influenza, and also partially associated after SARS-CoV-2 stimulation. In patients diagnosed with COVID-19, antibody responses after infection were significantly stronger if the volunteers had previously received BCG vaccine.CONCLUSIONS: BCG vaccination had no effect on the incidence of RTIs, including SARS-CoV-2 infection, in older adult volunteers. However, it improved cytokine responses stimulated by influenza and SARS-CoV-2 and induced stronger antibody titers after COVID-19 infection.CLINICAL TRIALS REGISTRATION: EU Clinical Trials Register 2020-001591-15 ClinicalTrials.gov NCT04417335.
KW - BCG vaccination
KW - COVID-19
KW - SARS-CoV-2
KW - trained immunity
UR - http://www.scopus.com/inward/record.url?scp=85137215560&partnerID=8YFLogxK
U2 - 10.1093/cid/ciac182
DO - 10.1093/cid/ciac182
M3 - Article
C2 - 35247264
SN - 1058-4838
VL - 75
SP - e938-e946
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 1
ER -