The role of hybrid immunity after the administration of the first booster dose

COVID-19 vaccines have been shown to be safe, effective and life-saving. However, the advent of the Omicron variant has greatly impacted the effectiveness of vaccination and the transmissibility of the virus requiring the analysis of the different factors leading to breakthrough infections. The aim of this study is to investigate, in a cohort of healthcare workers (HCWs), the role of hybrid immunity on the incidence of breakthrough infection after the administration of the first booster dose. This retrospective study was conducted in an Italian hospital from September 2021 to September 2022. Only HCWs who had received BNT162b2 vaccine and the first booster dose were included. Participants were assigned in the cohort of hybrid immunity if were infected prior to the administration of the first dose and completing the primary course, with a single inoculation, while in the other cohort individuals had received three doses of the vaccine. The risk of infection was estimated by means of the Nelson-Aalen cumulative risk function. Cox regression was applied to detect potentially interacting covariates. Out of 5.650 HCWs observed, 402 got infected before primary schedule (hybrid immunity). Comparing the two cohorts, individuals with a hybrid immunisation had a lower risk of becoming infected after the booster dose. At 30 weeks the cumulative risk was 50% in those with three vaccine doses against 30% in those with hybrid immunity, showing an increasing trend over time. The difference between the two curves in the log-rank test appears to be statistically significant (p < 0.001). Cox regression analysis confirmed the results (HR = 0.40; 95% CI, 0.35-0.57). These findings contribute robustly to the scientific debate on the comparison of protection conferred by the full vaccine cycle or by COVID-19 vaccines plus infection. The pandemic has highlighted the importance of rapidly generating clinical evidence that can allow regulatory agencies and HCWs to make informed decisions. KEY MESSAGES: • Hybrid immunity from previous infection and recent booster vaccination conferred the strongest protection against infection. • The data collected confirm the need for continuous monitoring of vaccine-induced immunogenicity and for establishing the exact timing of vaccination with more effective vaccination schedules.