TY - JOUR
T1 - The impact of circadian rhythm on Bacillus Calmette-Guérin vaccination effects on SARS-CoV-2 infections
AU - Föhse, Konstantin
AU - Taks, Esther J M
AU - Moorlag, Simone J C F M
AU - Bonten, Marc J M
AU - van Crevel, Reinout
AU - Ten Oever, Jaap
AU - van Werkhoven, Cornelis H
AU - Netea, Mihai G
AU - van de Maat, Josephine S
AU - Hoogerwerf, Jacobien J
N1 - Funding Information:
This work was investigator initiated and supported by the Radboud University Medical Center and the University Medical Center (UMC) Utrecht, Emergent Ventures (unconditional fast grant), the Mercator Center, George Mason University, Willem Bakhuys Roozeboomstichting, the European Research Council (advanced grant number 833247), and the Netherlands Organization for Scientific Research (Spinoza grant to MN). Acknowledgments
Publisher Copyright:
Copyright © 2023 Föhse, Taks, Moorlag, Bonten, van Crevel, ten Oever, van Werkhoven, Netea, van de Maat and Hoogerwerf.
PY - 2023/2/16
Y1 - 2023/2/16
N2 - BACKGROUND AND OBJECTIVE: A recent study has suggested that circadian rhythm has an important impact on the immunological effects induced by Bacillus Calmette-Guérin (BCG) vaccination. The objective of this study was to evaluate whether the timing of BCG vaccination (morning or afternoon) affects its impact on severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections and clinically relevant respiratory tract infections (RTIs).METHODS: This is a
post-hoc analysis of the BCG-CORONA-ELDERLY (NCT04417335) multicenter, placebo-controlled trial, in which participants aged 60 years and older were randomly assigned to vaccination with BCG or placebo, and followed for 12 months. The primary endpoint was the cumulative incidence of SARS-CoV-2 infection. To assess the impact of circadian rhythm on the BCG effects, participants were divided into four groups: vaccinated with either BCG or placebo in the morning (between 9:00h and 11:30h) or in the afternoon (between 14:30h and 18:00h).
RESULTS: The subdistribution hazard ratio of SARS-CoV-2 infection in the first six months after vaccination was 2.394 (95% confidence interval [CI], 0.856-6.696) for the morning BCG group and 0.284 (95% CI, 0.055-1.480) for the afternoon BCG group. When comparing those two groups, the interaction hazard ratio was 8.966 (95% CI, 1.366-58.836). In the period from six months until 12 months after vaccination cumulative incidences of SARS-CoV-2 infection were comparable, as well as cumulative incidences of clinically relevant RTI in both periods.CONCLUSION: Vaccination with BCG in the afternoon offered better protection against SARS-CoV-2 infections than BCG vaccination in the morning in the first six months after vaccination.
AB - BACKGROUND AND OBJECTIVE: A recent study has suggested that circadian rhythm has an important impact on the immunological effects induced by Bacillus Calmette-Guérin (BCG) vaccination. The objective of this study was to evaluate whether the timing of BCG vaccination (morning or afternoon) affects its impact on severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections and clinically relevant respiratory tract infections (RTIs).METHODS: This is a
post-hoc analysis of the BCG-CORONA-ELDERLY (NCT04417335) multicenter, placebo-controlled trial, in which participants aged 60 years and older were randomly assigned to vaccination with BCG or placebo, and followed for 12 months. The primary endpoint was the cumulative incidence of SARS-CoV-2 infection. To assess the impact of circadian rhythm on the BCG effects, participants were divided into four groups: vaccinated with either BCG or placebo in the morning (between 9:00h and 11:30h) or in the afternoon (between 14:30h and 18:00h).
RESULTS: The subdistribution hazard ratio of SARS-CoV-2 infection in the first six months after vaccination was 2.394 (95% confidence interval [CI], 0.856-6.696) for the morning BCG group and 0.284 (95% CI, 0.055-1.480) for the afternoon BCG group. When comparing those two groups, the interaction hazard ratio was 8.966 (95% CI, 1.366-58.836). In the period from six months until 12 months after vaccination cumulative incidences of SARS-CoV-2 infection were comparable, as well as cumulative incidences of clinically relevant RTI in both periods.CONCLUSION: Vaccination with BCG in the afternoon offered better protection against SARS-CoV-2 infections than BCG vaccination in the morning in the first six months after vaccination.
KW - BCG
KW - COVID-19
KW - SARS-CoV-2
KW - circadian clock
KW - circadian rhythm
KW - heterologous protection
KW - respiratory tract infection
KW - trained immunity
UR - http://www.scopus.com/inward/record.url?scp=85149583497&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2023.980711
DO - 10.3389/fimmu.2023.980711
M3 - Article
C2 - 36875134
SN - 1664-3224
VL - 14
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 980711
ER -