Long-Term Trends in the Protection Against Severe Courses of COVID-19 by Vaccination A Retrospective Observational Study in Older Persons During the Omicron Wave

Background: The long -term course of protection against severe COVID-19 courses by vaccine-induced or hybrid immunity in Germany is unclear. Methods: We studied 146 457 cases aged 60-99 years in the German federal state of Bavaria who were immunized against COVID-19 and tested positive for it from February 2022 to January 2023. We calculated adjusted hazard ratios for a severe course (hospitalization or death due to COVID-19) for different intervals between the onset of full primary or booster immunity and the date of the infection. Results: 3342 (2.3%) severe courses of COVID-19 were observed in the first 60 days after the infection. The risk of a severe course rose with the interval between the onset of immune protection and the infection (adjusted hazard ratios and 95% confidence intervals at 6, 9, 12, and 15 months: 1.14 [1.08; 1.20]; 1.33 [1.24; 1.42]; 1.39 [1.25; 1.54]; 1.61 [1.35; 1.93]). The risk rose more slowly when mRNA-based vaccines were used exclusively. In a previous study, we observed 82% initial efficacy in cases aged 60 and above who received a booster vaccination (compared to unvaccinated cases) and an absolute risk reduction of 2.1%. If one extrapolates these findings to the current study, the residual efficacy and absolute risk reduction are found to be approximately 71% and 1.8% (respectively) at 6 months, and 32% and 0.8% at 15 months. Conclusion: These results indicate that, during the Omicron wave, the protection of older persons against a severe COVID-19 course gradually declined from six months after vaccination onward. The limitations of this study include confounders that could not be taken into account, possible misclassification of the cause of death, and selection bias due to missing information about vaccination status and severe COVID-19 courses.