Immune Responses to SARS-CoV-2 Infection and Vaccination in Dialysis Patients and Kidney Transplant Recipients

Abstract

Dialysis patients and kidney transplant (KTX) recipients suffer from an impaired immune system and show a decreased response to the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination. We performed a retrospective analysis of 1505 serological SARS-CoV-2 measurements obtained from 887 dialysis patients and 86 KTX recipients. The results were separated by patient subgroups (dialysis/KTX) as well as SARS-CoV-2 status. The latter criterion included SARS-CoV-2-naïve patients with or without COVID-19 vaccination and convalescent patients receiving a booster shot. Serologies of 27 vaccinated healthy individuals served as the reference group. Vaccine-induced cellular immune response was quantified by an interferon-γ release assay in 32 KTX recipients. We determined seroconversion rates of 92.6%, 93.4%, and 71.4% in dialysis patients vaccinated with either BNT162b2, mRNA-1273, or AZD1222, respectively. Vaccination-induced anti-SARS-CoV-2 antibody titers were lower in dialysis patients compared to healthy individuals, and vaccination with mRNA-1273 induced higher titers than BNT162b2. The initial seroconversion rate was 39.5% in KTX recipients vaccinated with BNT162b2. A linear regression model identified medication with mycophenolate-mofetil/mycophenolic acid as an independent risk factor for missing seroconversion. Within a cohort of 32 KTX recipients, cellular and humoral immune reactivity to SARS-CoV-2 was detectable in three patients only. Conclusively, vaccine-induced seroconversion rates were similar in dialysis patients compared to healthy individuals but were strongly impaired in KTX recipients. Anti-SARS-CoV-2 IgG titers elicited by double active immunization were significantly lower in both cohorts compared to healthy individuals, and immune responses to vaccination vanished quickly.

Keywords: COVID-19; antibodies; immunosuppression; kidney disease; protection; titer.

Figure 1

A systematic analysis of vaccine- and infection-induced humoral SARS-CoV-2 immune responses in dialysis patients and kidney transplant recipients. (A) SARS-CoV-2 surveillance in SARS-CoV-2-naïve dialysis patients. (B) Vaccine-induced humoral response in SARS-CoV-2-naïve dialysis patients. (C) Booster shot-induced humoral response in SARS-CoV-2 convalescent dialysis patients. (D) Vaccine-induced humoral response in SARS-CoV-2-naïve kidney transplant recipients. Vaccines used: BNT162b2 (BioNTech/Pfizer, Mainz, Germany/New York, NY, USA), mRNA-1273 (Moderna, CA, USA), AZD1222 (AstraZeneca/University of Oxford, Cambridge/Oxford, UK). SARS-CoV-2: severe acute respiratory syndrome coronavirus type 2.

Figure 2

Vaccine- and infection-induced humoral response quantified by anti-SARS-CoV-2 IgG titers in dialysis patients compared to vaccinated healthy individuals. (A) Vaccine-induced anti-SARS-CoV-2 IgG titers in dialysis patients differ significantly between dialysis patients immunized by BNT162b2, mRNA-1273, and AZD1222 compared to the reference cohort of mRNA-1273 vaccinated healthy individuals. (B) Infection induced anti-SARS-CoV-2 IgG titers in convalescent dialysis patients with (w) and without (w/o) booster shot immunization using BNT162b2 mRNA are reduced compared to vaccine-induced titer in healthy individuals. (C) Booster shot-induced anti-SARS-CoV-2 IgG titers in SARS-CoV-2-recovered dialysis patients are elevated compared to mRNA vaccine-induced titers in SARS-CoV-2-naïve dialysis patients. Vaccines used: BNT162b2 (BioNTech/Pfizer, Mainz, Germany/New York, NY, USA), mRNA-1273 (Moderna, CA, Unites States), and AZD1222 (AstraZeneca/University of Oxford, Cambridge/Oxford, UK) in dialysis patients; mRNA-1273 (Moderna, CA, Unites States) in healthy individuals. A Kruskal-Wallis test across all groups was used to indicated differences to healthy individuals. Mann–Whitney U test was used to indicated differences between two groups (*** p < 0.001 and **** p < 0.0001). Data are represented as median ± interquartile range and each patient is depicted by a single dot. IgG: immunoglobulin G; BAU: binding antibody unit; SARS-CoV-2: severe acute respiratory syndrome coronavirus type 2.

Figure 3

Vaccine-induced humoral response quantified by anti-SARS-CoV-2 IgG titers in kidney transplant recipients and healthy individuals. (A) Vaccine-induced anti-SARS-CoV-2 IgG titers in kidney transplant recipients are impaired compared to healthy individuals. (B) Vaccine-induced anti-SARS-CoV-2 IgG titers are significantly elevated in kidney transplant recipients with immunosuppression lacking mycophenolate mofetil/mycophenolic acid. Vaccines used: BNT162b2 (BioNTech/Pfizer Mainz, Germany/New York, NY, USA) in kidney transplant recipients, and mRNA-1273 (Moderna, CA, United States) in healthy individuals. A Kruskal–Wallis test across all groups was used to indicate differences with respect to healthy individuals. A Mann–Whitney U test was used to indicate differences between two groups (**** p < 0.0001). Data are represented as median ± interquartile range and each patient is depicted by a single dot. IgG: immunoglobulin G; BAU: binding antibody unit; KTX: kidney transplant recipient; MMF: mycophenolate mofetil; MPA: mycophenolic acid; SARS-CoV-2: severe acute respiratory syndrome coronavirus type 2.