Longitudinal dynamics of humoral immune responses following serial COVID-19 vaccinations and breakthrough infections in dialysis patients

Patients with end-stage kidney disease (ESKD) undergoing dialysis have impaired vaccine responses. Many countries recommend extended primary series and regular COVID-19 boosters for this group, but data on long-term humoral responses after repeated doses or breakthrough infection are limited. In this prospective cohort study of 498 dialysis patients, most received homologous ChAdOx1 nCoV-19 as a primary series, mRNA-1273 for the third and fourth doses, and bivalent Moderna vaccines for later doses. Neutralizing antibodies (via surrogate virus neutralization test) and anti - receptor-binding domain (RBD) antibodies were measured up to 15 months post-vaccination or infection. The primary endpoint was seroprotection (neutralization inhibition ≥30%); the secondary was anti-RBD seroprotection (≥100 U/mL). Seroprotection increased from 16% (neutralizing) and 2% (anti-RBD) after the first dose to ~100% after the third and subsequent doses. Neutralizing inhibition rose from 5% (dose 1) to ~90% (doses 4-6). Anti-RBD titers declined 66%-85% by 6 months and >90% by 12-15 months. Younger age, receipt of a fourth dose, and vaccine platform were significant predictors of neutralizing titers. Breakthrough infection led to higher and more sustained anti-RBD titers, particularly in patients with hybrid immunity. Patients with stronger immunity had fewer symptoms. In conclusion, serial COVID-19 vaccinations elicited robust humoral responses in dialysis patients, with younger age, receipt of a booster dose, and vaccine platform, emerging as significant predictors. Although antibody titers declined over time, they were better maintained in those with hybrid immunity. These findings support the implementation of personalized booster strategies to optimize protection in immunocompromised populations.