Short summaryWe investigated changes in serologic measurements after COVID-19 vaccination in 19,422 subjects. An individual-level analysis was performed on standardized measurements. Age, infection, vaccine doses, time between doses and serologies, and vaccine type were associated with changes in serologic levels within 13 months.BackgroundPersistence of vaccine immunization is key for COVID-19 prevention.MethodsWe investigated the difference between two serologic measurements of anti-COVID-19 S1 antibodies in an individual-level analysis on 19,422 vaccinated healthcare workers (HCW) from Italy, Spain, Romania, and Slovakia, tested within 13 months from first dose. Differences in serologic levels were divided by the standard error of the cohort-specific distribution, obtaining standardized measurements. We fitted multivariate linear regression models to identify predictors of difference between two measurements.ResultsWe observed a progressively decreasing difference in serologic levels from <30 days to 210–240 days. Age was associated with an increased difference in serologic levels. There was a greater difference between the two serologic measurements in infected HCW than in HCW who had never been infected; before the first measurement, infected HCW had a relative risk (RR) of 0.81 for one standard deviation in the difference [95% confidence interval (CI) 0.78–0.85]. The RRs for a 30-day increase in time between first dose and first serology, and between the two serologies, were 1.08 (95% CI 1.07–1.10) and 1.04 (95% CI 1.03–1.05), respectively. The first measurement was a strong predictor of subsequent antibody decrease (RR 1.60; 95% CI 1.56–1.64). Compared with Comirnaty, Spikevax (RR 0.83, 95% CI 0.75–0.92) and mixed vaccines (RR 0.61, 95% CI 0.51–0.74) were smaller decrease in serological level (RR 0.46; 95% CI 0.40–0.54).ConclusionsAge, COVID-19 infection, number of doses, time between first dose and first serology, time between serologies, and type of vaccine were associated with differences between the two serologic measurements within a 13-month period.