AUTHOR=Föhse Konstantin , Taks Esther J.M. , Moorlag Simone J. C. F. M. , Bonten Marc J. M. , van Crevel Reinout , ten Oever Jaap , van Werkhoven Cornelis H. , Netea Mihai G. , van de Maat Josephine S. , Hoogerwerf Jacobien J. TITLE=The impact of circadian rhythm on Bacillus Calmette-Guérin vaccination effects on SARS-CoV-2 infections JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.980711 DOI=10.3389/fimmu.2023.980711 ISSN=1664-3224 ABSTRACT=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

Although 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.