The impact of circadian rhythm on Bacillus Calmette-Guérin vaccination effects on SARS-CoV-2 infections

Frontiers in Immunology

Immunology

Esther J.M. Taks¹  Reinout van Crevel¹  Jaap ten Oever¹  Simone J. C. F. M. Moorlag¹  Jacobien J. Hoogerwerf¹  Josephine S. van de Maat¹  Konstantin Föhse¹  Mihai G. Netea²  Cornelis H. van Werkhoven³  Marc J. M. Bonten³ 

[1] Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands;Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands;Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands;Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands;Department of Immunology and Metabolism, Life & Medical Sciences Institute, University of Bonn, Bonn, Germany;Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands;

关键词: COVID-19;    respiratory tract infection;    circadian rhythm;    BCG;    trained immunity;    heterologous protection;    SARS-CoV-2;    circadian clock;   

DOI  :  10.3389/fimmu.2023.980711

 received in 2022-06-28, accepted in 2023-02-03,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background and objectiveA 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).MethodsThis 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).ResultsThe 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.ConclusionAlthough there was a difference in effect between morning and afternoon BCG vaccination, the vaccine did not protect against SARS-COV-2 infections and clinically relevant RTI’s at either timepoint.

【 授权许可】

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Copyright © 2023 Föhse, Taks, Moorlag, Bonten, van Crevel, ten Oever, van Werkhoven, Netea, van de Maat and Hoogerwerf