Impaired Immune Response to SARS-CoV-2 Vaccination in Dialysis Patients and in Kidney Transplant Recipients

Abstract

Background: Patients with kidney failure on dialysis or after renal transplantation have a high risk for severe COVID-19 infection, and vaccination against SARS-CoV-2 is the only expedient prophylaxis. Generally, immune responses are attenuated in patients with kidney failure, however, systematic analyses of immune responses to SARS-CoV-2 vaccination in patients on dialysis and in kidney transplant recipients (KTRs) are still needed.

Methods: In this prospective, multicentric cohort study, antibody responses to COVID-19 mRNA vaccines (BNT162b2 [BioNTech/Pfizer] or mRNA-1273 [Moderna]) were measured in 32 patients on dialysis and in 28 KTRs. SARS-CoV-2-specific antibodies and neutralization capacity were evaluated and compared with controls (n=78) of a similar age range.

Results: After the first vaccination, SARS-CoV-2-specific antibodies were nearly undetectable in patients with kidney failure. After the second vaccination, 93% of the controls and 88% of patients on dialysis but only 37% of KTRs developed SARS-CoV-2-specific IgG above cutoff. Moreover, mean IgG levels were significantly lower in KTRs (54±93 BAU/ml) compared with patients on dialysis (503±481 BAU/ml; P<0.01). Both KTRs and patients on dialysis had significantly lower IgG levels compared with controls (1992±2485 BAU/ml; P<0.001 and P<0.01, respectively). Importantly, compared with controls, neutralizing antibody titers were significantly lower in KTRs and patients on dialysis. After the second vaccination, 76% of KTRs did not show any neutralization capacity against SARS-CoV-2, suggesting impaired seroprotection.

Conclusions: Patients with kidney failure show a significantly weaker antibody response compared with controls. Most strikingly, only one out of four KTRs developed neutralizing antibodies against SARS-CoV-2 after two doses of vaccine. These data suggest that vaccination strategies need modification in KTRs and patients on dialysis.Clinical Trial registry name and registration number: Vaccination Against COVID-19 in Chronic Kidney Disease, NCT04743947.

Keywords: COVID-19; SARS-CoV-2 specific antibody; clinical immunology; humoral immune response; immunity; kidney failure; kidney transplantation; renal insufficiency; transplantation; vaccination; virology.

Conflict of interest statement

L.C. Rump reports having consultancy agreements with, and receiving honoraria from, Bayer, Boehringer, Medtronic, and ReCor. M. Schmitz reports receiving honoraria from Daiichi-Sankyo. J. Stegbauer reports having other interests in/relationships with American Heart Association High Blood Pressure, German Society of Nephrology, and German Society of Hypertension; receiving honoraria from AstraZeneca, Bayer Life Science, and Boehringer; serving on the editorial board of Experimental and Clinical Endocrinology & Diabetes and Kidney360; and receiving research funding from German Research Foundation. All remaining authors have nothing to disclose.

Copyright © 2021 by the American Society of Nephrology.

Figures

Graphical abstract

Figure 1.

Anti SARS-CoV-2 spike protein-specific antibody titers after first and second vaccination. Antibody titers >35.2 BAU/ml were considered a positive immune response to vaccination. Antibody titers below the detection limit were set to 1.0. Antibody titers after the (A) first and (B) second vaccination were significantly higher in controls compared with patients on dialysis and kidney transplant recipients (KTRs). Moreover, mean antibody titers after the second vaccination were significantly lower in KTRs compared with the dialysis group. For comparison of three groups, data were analyzed by the nonparametric Kruskal–Wallis Test with post hoc Dunn test. *P<0.05, **P<0.01, ***P<0.001. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2.

Median titer and frequency of neutralizing antibodies after second vaccination. (A) The mean titers of neutralizing antibodies were significantly lower in patients on dialysis and KTRs, compared with controls, after the second vaccination. (B) Frequencies of neutralizing antibodies in controls, patients on dialysis, and KTRs after the second vaccination. For comparison of three groups, data were analyzed by the nonparametric Kruskal–Wallis test with post hoc Dunn test. **P<0.01, ***P<0.001. NT, neutralization titer.

Figure 3.

Frequencies of the side effects after the first and second vaccination.