Immunogenicity of COVID-19 Vaccination in Patients With End-Stage Renal Disease Undergoing Maintenance Hemodialysis: The Efficacy of a Mix-and-Match Strategy

Abstract

Background: The objective of this study was to evaluate the immunogenicity of coronavirus disease 2019 (COVID-19) vaccination in patients with end-stage renal disease (ESRD) on hemodialysis.

Methods: ESRD patients at the hemodialysis center of a tertiary-care university-affiliated hospital and healthy employees at the clinical laboratory center were prospectively recruited between March and June 2021. For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody analysis, blood samples were collected serially on days 0, 14, 28, and 56 after the first vaccine dose, and on days 7 and 50 after the second dose. Antibodies against the SARS-CoV-2 spike protein were quantified, and SARS-CoV-2 neutralizing antibodies were measured in the serum and plasma.

Results: Thirty-one ESRD patients and 55 healthy employees were regularly monitored. Twenty-five (80.6%) ESRD patients on hemodialysis received a mix-and-match strategy with ChAdOx1-BNT162b2 (AZ-Pf group) and six (19.4%) received two doses of ChAdOx1 (AZ-AZ group). ESRD patients on hemodialysis showed lower binding antibody titers and neutralizing antibody activities compared to healthy participants following the first vaccination with ChAdOx1. After the second dose, AZ-Pf group had higher immunogenicity than healthy people on days 7 and 50. The binding antibody titer and neutralizing antibody activities on days 7 and 50 were significantly higher in the AZ-Pf group than in the AZ-AZ group.

Conclusion: ESRD patients on hemodialysis receiving the mix-and-match strategy (ChAdOx1-BNT162b2) have COVID-19 vaccine immunogenicity comparable to healthy individuals receiving two doses of ChAdOx1.

Trial registration: ClinicalTrials.gov Identifier: NCT04871945.

Keywords: COVID-19; ESRD; Mix-and-Match; Vaccine.

Fig. 1. Comparison of immunogenicity of COVID-19 vaccination between healthy people and patients with ESRD on hemodialysis.

(A) Binding antibody titer measured by Elecsys^® Anti-SARS-CoV-2 S. (B) Neutralizing antibody activity measured by cPass™ SARS-CoV-2 Neutralization Antibody Detection Kit. (C) Neutralizing antibody activity measured by R-FIND SARS-CoV-2 Neutralizing Antibody ELISA. (D) Proportion of participants with a positive result of binding antibody measured by Elecsys® Anti-SARS-CoV-2 S. (E) Proportion of participants with a positive result of neutralizing antibody measured by cPass™ SARS-CoV-2 Neutralization Antibody Detection Kit. (F) Proportion of participants with a positive result of neutralizing antibody measured by R-FIND SARS-CoV-2 Neutralizing Antibody ELISA. COVID-19 = coronavirus disease 2019, ESRD = end-stage renal disease, SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2, ELISA = enzyme-linked immunosorbent assay, E = patients with ESRD, H = healthy people. ^aP values are the result of Mann–Whitney U test; ^bP values are the result of Wilcoxon signed-rank test; and ^cP values are the result of the Cochrane–Armitage test for trend.

Fig. 2. Comparison of immunogenicity of COVID-19 vaccination between patients with ESRD on hemodialysis who received ChAdOx1–BNT162b2 and those who received two doses of ChAdOx1.

(A) Binding antibody titer measured by Elecsys^® Anti-SARS-CoV-2 S. (B) Neutralizing antibody activity measured by cPass™ SARS-CoV-2 Neutralization Antibody Detection Kit. (C) Neutralizing antibody activity measured by R-FIND SARS-CoV-2 Neutralizing Antibody ELISA. (D) Change in the level of binding antibody between day 56 from the first dose and day 7 from the second dose measured by Elecsys^® Anti-SARS-CoV-2 S. (E) Change in the level of neutralizing antibody between day 56 from the first dose and day 7 from the second dose measured by cPass™ SARS-CoV-2 Neutralization Antibody Detection Kit. (F) Change in the level of neutralizing antibody between day 56 from the first dose and day 7 from the second dose measured by R-FIND SARS-CoV-2 Neutralizing Antibody ELISA. COVID-19 = coronavirus disease 2019, ESRD = end-stage renal disease, SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2, ELISA = enzyme-linked immunosorbent assay, Vec = ChAdOx1, mRNA = BNT162b2, E = patients with ESRD, H = healthy people. ^aP values are the result of Mann–Whitney U test.

Fig. 3. Adverse effects after COVID-19 vaccination.

(A) Comparison between healthy people and patients with ESRD on hemodialysis. (B) Comparison between patients with ESRD on hemodialysis who received ChAdOx1–BNT162b2 and those who received two doses of ChAdOx1. COVID-19 = coronavirus disease 2019, ESRD = end-stage renal disease. ^aP value <0.05.

Fig. 4. Cumulative incidence function curves of COVID-19 vaccination humoral immunogenicity stratified by (A) patient with GN as underlying cause of hemodialysis, (B) steroid treatment, (C) Corr Ca, and (D) CRP.

COVID-19 = coronavirus disease 2019, GN = glomerulonephritis, Adj HR = adjuster hazard ratio, CI = confidential interval, Corr Ca = corrected serum calcium, CRP = C-reactive protein. ^aAdjusted for age and sex; ^bEvaluate hypotheses of equality of cause-specific cumulative incidence functions between two groups; ^cDefined as a SARS-CoV-2 nAbs ≥ 30% inhibition at each specific time points.