Abstract Background Healthcare workers (HCWs) are essential frontline responders to public health emergencies and are one of the risk groups targeted by annual vaccination campaigns. Serological studies are valuable for high-risk groups such as HCWs, as they contribute to assess vulnerability, monitor infection control measures, and guide vaccination strategies in high-risk settings. This study aimed to assess humoral response at baseline, 3 and 6 months after the 2023–2024 COVID-19 vaccination campaign in HCWs, and to identify demographic and clinical factors associated with variations in antibody levels over time. Methods Prospective cohort study of vaccinated HCWs at a central hospital in Portugal (September 2023–May 2024). Serial serological tests to assess anti-spike receptor-binding domain (anti-RBD/S) and anti-nucleocapsid protein (anti-N) IgG antibodies were used to monitor the immune response and SARS-CoV-2 infection history, respectively. Wilcoxon signed-rank tests were used to assess changes in antibody levels over time, and linear regression models were used to identify factors associated with variations in SARS-CoV-2 anti-RBD/S IgG concentrations, on the basis of available demographic and clinical data. Results In a cohort of 166 HCWs who received the 2023–2024 COVID-19 booster vaccine, anti-RBD/S IgG antibody levels significantly increased at 3 months post-vaccination (16 007.4 vs. 30 572.9 AU/mL) before declining by 6 months (18 327.3 AU/mL), nearing baseline levels. Previous infection (β = 1.92, 95% CI: 1.33-2.77) and older age (β = 2.65, 95%CI: 1.64‐4.29) were associated with higher antibody concentrations at baseline, whereas smoking was linked to lower antibody levels at 6 months (β = 0.32, 95%CI: 0.11–0.88). Other factors, such as sex and chronic conditions, had no consistent significant impact over time. Conclusions Although SARS-CoV-2 anti-RBD/S IgG antibody concentrations declined significantly six months after the 2023–2024 COVID-19 booster vaccination, they remained at relatively high concentrations over the follow-up period. This study provides new insight into these dynamics in a highly vaccinated and exposed HCWs cohort during a later post-pandemic phase, highlighting the influence of prior infection, age, and smoking on antibody persistence and reinforces the relevance of ongoing immune monitoring of this risk group to guide tailored control strategies. However, vaccine effectiveness studies in highly exposed and vaccinated populations, such as HCWs, are needed to better inform the role of antibody monitoring in this context, especially given the ongoing trend of annually updated vaccines. Clinical trial Not applicable.
Santos et al. (2026) studied this question.