Humoral Response to the Third Dose of SARS-CoV-2 Vaccine Among Dialysis Patients: A Breakthrough Infection Case–Control Study

<b>Background:</b> COVID-19 vaccination and subsequent booster doses became critical components of public health strategies to control the pandemic and reduce disease severity, especially in fragile individuals. Among these, subjects undergoing dialysis represent one of the highly vulnerable populations. <b>Methods:</b> We conducted a multicenter case-control study among dialysis patients between March 2021 and May 2022 (study population n = 3264). We evaluated anti-S/RBD-IgG and anti-SARS-CoV-2 neutralizing antibodies before (T3) and after (T4) the third dose in individuals with a COVID-19 diagnosis after the third dose (cases) and in those who did not report infection (controls). <b>Results:</b> The study included 187 cases and 150 controls. Serological analysis showed a significant increase (<i>p</i> < 0.001) in anti-SARS-CoV-2 antibody levels after the third vaccine dose (from T3 to T4) in both groups. At T3, with the same number of days between the second dose and T3, the antibody levels detected were significantly lower in cases as compared to controls. At T4, we observed similar antibody titers in the two groups. Notably, the mean difference in time from the third dose to T4 was significantly greater in controls (73.0 days vs. 36.7, <i>p</i> < 0.001), suggesting a reduced antibody waning in controls. Accordingly, multivariate analysis showed that the risk of infection was considerably reduced by the pre-third-dose antibody levels. <b>Conclusions:</b> This study reinforces the critical role of the humoral response in preventing infections in the vulnerable population of dialysis patients. Regular monitoring of antibody levels and timely administration of booster doses are essential to optimize protection in this group.