Local and Systemic Immunity Are Impaired in End-Stage-Renal-Disease Patients Treated With Hemodialysis, Peritoneal Dialysis and Kidney Transplant Recipients Immunized With BNT162b2 Pfizer-BioNTech SARS-CoV-2 Vaccine

Abstract

Vaccination against COVID-19 in patients with end-stage renal disease (ESRD) on replacement therapy and kidney transplant recipients (KTRs) is particularly important due to the high mortality rate. Here, we tested the local and systemic immunity to the novel Pfizer BioNTech (BNT162b2) messenger RNA (mRNA) in ESRD, KTR patients, and healthy individuals (150 subjects). The ESRD group was divided into: hemodialysis (HD) and peritoneal dialysis (PD). We investigated the local and systemic immunity based on anti-N (nucleoprotein) and anti-S (spike1/2) Immunoglobulin A (IgA) and Immunoglobulin G (IgG) antibodies, respectively. Additionally, we performed an Interferon gamma (IFN-γ) release test Interferon-gamma release assay (IGRA) to monitor the cellular component of vaccine response. The control group had the highest level of anti-S IgG antibodies (153/2,080 binding antibody units (BAU)/ml) among all analyzed patients after the 1st and 2nd dose, respectively. The HD group (48/926 BAU/ml) had a diminished antibody level compared to PD (93/1,607 BAU/ml). Moreover, the seroconversion rate after the 1st dose was lower in HD than PD (56% vs. 86%). KTRs had extremely low seroconversion (33%). IgA-mediated immunity was the most effective in the control group, while other patients had diminished IgA production. We observed a lower percentage of vaccine responders based on the IFN-γ level in all research participants (100% vs. 85% in control, 100% vs. 80% in PD, 97% vs. 64% in HD). 63% of seropositive KTRs had a positive IGRA, while 28% of seronegative patients produced IFN-γ. Collectively, PD patients had the strongest response among ESRD patients. Two doses of the Pfizer vaccine are ineffective, especially in HD and KTRs. A closer investigation of ESRD and KTRs is required to set the COVID-19 vaccine clinical guidance.

Clinical trial registration number: www.ClinicalTrials.gov, identifier: NCT04 905 862.

Trial registration: ClinicalTrials.gov NCT04905862.

Keywords: COVID-19; SARS-CoV-2; hemodialysis; peritoneal dialysis; transplantation.

Figure 1

Study cohort and the overall research design.

Figure 2

The level of anti-S IgG (BAU/ml) and the percentage of seroconversion rate after the BNT162b vaccine. (A) Increase in anti-S IgG antibodies (BAU/ml) after the second dose of the BNT162b2 vaccine in all analyzed groups. Four sections based on the type of the group are shown: control, HD, PD, and KTX. Both antibody titers (BAU/ml) after the first (1st) and the second (2nd) are presented. The red line indicates the median. Statistical comparisons across groups were performed with the Kruskal–Wallis test. In control and HD and PD groups, we observed the highest increase in anti-S IgG after the whole course of vaccination, while in the KTX group, the antibody production was particularly diminished. (B) Antibody levels (BAU/ml) after the first dose of vaccine in control, HD, PD, and KTX. The control group had the highest anti-S IgG; however, significant results with the performance of the Kruskal–Wallis test were obtained between control and HD and KTX groups. The KTX group had the lowest response, and statistical significance was present between this group and all other research participants. Among dialysis patients, the PD group had significantly higher anti-S IgG compared to HD patients. The same conclusions were made after the second (C) dose of vaccine where the control and PD groups had the higher response in comparison with the HD and KTX groups. (D) On the left: seroconversion rate after the first dose, on the right: seroconversion rate after the second dose. The cut-off for the positive seroconversion rate for anti-S IgG was ≥39 BAU/ml. The circle divides patients into: responders (red—positive anti-S IgG titer after vaccine) and non-responders (black—patients without anti-S IgG). The detailed data (percentage) collects the number of patients with positive seroconversion. HD, hemodialysis; PD, peritoneal dialysis; KTX, kidney transplant recipients.

Figure 3

The level of anti-S IgA (unit/ml) after the first (A) and the second (B) dose of BNT162b2 vaccine The p-value was calculated with the use of the Kruskal–Wallis test. Dunn’s multiple comparison test with the reference to the control group (highlighted in blue) was used as a post-hoc test. The red line indicates the median. Significant results are marked with * (p<0.05), ** (p<0.01), or *** (p<0.001). After the first (A) as well as the second (B) dose of vaccine, we detected differences between the control group and patients with renal disorders. We did not observe any statistical significance among renal disease patients both after the first and second dose of vaccine. HD, hemodialysis; PD, peritoneal dialysis; KTX, kidney transplant.

Figure 4

Cellular immune response in analyzed groups measured with the use of IGRA test (A) The level (mIU/ml) of secreted INF-γ after PBMC stimulation with SARS-CoV-2 S protein after the whole course of vaccination. The red line indicates the median. Statistical comparisons across groups were performed with the Kruskal–Wallis test. Dunn’s multiple comparison test with the reference to the control group (highlighted in blue) was used as a post-hoc test. Significant results are marked with * (p<0.05), ** (p<0.01), or *** (p<0.001). Similar to anti-S IgG data in the HD group, we observed two subpopulations. Namely, in the black circles, patients with positive IGRA are collected. The analysis has shown the lower age and CCI index in the group of HD patients with high INF-γ secretion [age (p=0.3846) – median 60 (39–75) vs. 70 (22–94), CCI (p=0.3759)—median 4,5 (2–10) vs. 7 (1–11)]. (B) The percentage of positive IGRA patients. The circle divides patients into: IGRA positive (red) and IGRA negative (black). The detailed data (percentage) collects the number of patients with a positive IGRA test. The KTX group is additionally divided into: responders (anti-S IgG levels ≥39 BAU/ml) and non-responders (anti-S IgG levels <39 BAU/ml). HD, hemodialysis; PD, peritoneal dialysis; KTX, kidney transplant recipients.