Longitudinal Characterization of SARS-CoV-2 Immunity in Hemodialysis Patients Post Omicron

Introduction: Individuals receiving hemodialysis (HD) are at risk for severe COVID-19 and have attenuated responses to COVID-19 vaccines. Evolution of immunity and risk for subsequent infection with additional vaccinations and infections in this population is poorly understood. Methods: An observational multicenter cohort of 55 patients receiving HD in community HD centers, majority (85%) with at least 2 doses of COVID-19 vaccine (56% female, age [median; interquartile range, IQR] of 67, [58.0–74.0] years), was followed-up with for 50 weeks between December, 2021 and April, 2023 and collected blood samples at enrollment, 8 weeks, and 24 weeks thereafter. Anti-SARS-CoV-2 IgG and ACE2 inhibition (surrogate neutralization) against ancestral, Delta, and Omicron subvariants was measured. T-cell responses to Spike and Mucleocapsid proteins were measured via enzyme-linked immunosorbent spot. Changes in antibody and T cell responses were assessed by paired Wilcoxon rank-sum testing and Fisher exact testing. Antibody responses were compared to thrice vaccinated healthy controls (HCs) as a benchmark for what optimal responses could have been in the early Omicron period. Results: Neutralization did not increase over time, and HD participants had lower neutralization than HCs. Only 56% of HD participants had a positive T cell response to spike after the BA.1/2 wave. Antibody and cellular responses were concordant in only 34.5% at final visit. Antibody responses trended higher among those with prior COVID-19, but spike-specific T cell responses did not vary. Conclusions: Original vaccine formulations and previous infection are insufficient to induce reliable SARS-CoV-2 responses in individuals on HD, suggesting that updated annual COVID-19 vaccines and transmission-based precautions remain critical in this population.