Hybrid and vaccination immunity against severe COVID-19 in the post-pandemic era—a retrospective cohort study

Objectives: As COVID-19 has transitioned to an endemic disease, there is a need for evidence-based effective strategies to mitigate its public health impacts. This study aims to evaluate the protection offered by vaccination and hybrid immunity, particularly among the elderly, against severe disease by considering their immunological history and individual characteristics. Methods: In a retrospective cohort study, data from the Israeli Ministry of Health (May 2022–April 2024) were analysed, including 1.2 million individuals aged 60 years and older who received at least three COVID-19 vaccine doses. Participants were categorized into two groups: those with hybrid immunity and those with vaccination and without documented previous infection. Poisson regression models, adjusted for age, sex, wave period, and time since the last immunological event, were used to estimate the risk of severe COVID-19. Results: Individuals without documented previous infection are 14.4 (95% CI, 13.2−15.7) times more at risk compared with those with hybrid immunity. Those aged 70–80 and 80+ are 3.7 (95% CI, 3.0–4.5) and 11.3 (95% CI, 9.3–13.7) times more at risk, respectively, than those aged 60–64. Males are at 1.6 (95% CI, 1.5–1.7) times higher risk than females. There is a substantial decrease over time in severe cases. Waning immunity is observed in the 3–6 months cohort, which is 1.8 (95% CI, 1.5–2.2) times more likely to develop severe disease than the 0–3 months cohort. No further waning immunity was observed after that. Discussion: At this post-pandemic stage, individuals with hybrid immunity had a significantly lower risk of severe disease. These findings support the prioritization of protection strategies for individuals without hybrid immunity and suggest that protection remains durable for at least one year.