Early Humoral Responses of Hemodialysis Patients after COVID-19 Vaccination with BNT162b2

Abstract

Background and objectives: Patients receiving hemodialysis are at high risk for both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe coronavirus disease 2019. A lifesaving vaccine is available, but sensitivity to vaccines is generally lower in patients on dialysis. Little is yet known about antibody responses after coronavirus disease 2019 (COVID-19) vaccination in this vulnerable group.

Design, setting, participants, and measurements: In this prospective single-center study, we included 22 patients on dialysis and 46 healthy controls from Heidelberg University Hospital between December 2020 and February 2021. We measured anti-S1 IgG with a threshold index for detection greater than one, neutralizing antibodies with a threshold for viral neutralization of ≥30%, and antibodies against different SARS-CoV2 fragments 17-22 days after the first dose and 18-22 days after the second dose of the mRNA vaccine BNT162b2.

Results: After the first vaccine dose, four of 22 (18%) patients on dialysis compared with 43 of 46 (93%) healthy controls developed positive anti-S1 IgG, with a median anti-S1 IgG index of 0.2 (interquartile range, 0.1-0.7) compared with nine (interquartile range, 4-16), respectively. SARS-CoV2 neutralizing antibodies exceeded the threshold for neutralization in four of 22 (18%) patients on dialysis compared with 43 of 46 (93%) healthy controls, with a median percent inhibition of 11 (interquartile range, 3-24) compared with 65 (interquartile range, 49-75), respectively. After the second dose, 14 of 17 (82%) patients on dialysis developed neutralizing antibodies exceeding the threshold for viral neutralization and antibodies against the receptor binding S1 domain of the spike protein, compared with 46 of 46 (100%) healthy controls, respectively. The median percent inhibition was 51 (interquartile range, 32-86) compared with 98 (interquartile range, 97-98) in healthy controls.

Conclusions: Patients receiving long-term hemodialysis show a reduced antibody response to the first and second doses of the mRNA vaccine BNT162b2. The majority (82%) develop neutralizing antibodies after the second dose but at lower levels than healthy controls.

Keywords: COVID-19; SARS-CoV-2; dialysis; hemodialysis; humoral response; vaccination.

Graphical abstract

Figure 1.

Spike antigen–specific severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG levels of patients on hemodialysis and healthy controls after vaccination with BNT162b2. SARS-CoV-2 IgG antibodies represented logarithmically as an anti–S1-IgG index in all and in age-matched healthy controls and patients on dialysis after the first (A and B) and after the second (C and D) coronavirus disease 2019 (COVID-19) vaccination. Individual SARS-CoV-2 IgG antibody courses in all (E) and in age-matched (F) individuals after the first and after the second COVID-19 vaccination. The dashed red lines represent the cutoff for detection according to the manufacturer’s instructions. A semiquantitative index of less than one was classified as negative, and a value of one or higher was classified as positive. ***P<0.001.

Figure 2.

IgG antibodies against different SARS-CoV-2 target antigens of patients on hemodialysis and healthy controls after vaccination with BNT162b2. Detection of antibodies against the full spike protein (A), the S1 spike protein (B), the receptor binding domain (RBD) of the spike protein (C), the S2 spike protein (D), and the nucleocapsid protein (E) of SARS-CoV-2 in patients on dialysis and age-matched healthy controls after a median of 20 days after the second vaccine dose. The x axes represent the sample number, and the y axes represent the mean fluorescence intensity (MFI) value of the reactivity. The dashed red lines represent the cutoffs. ***P<0.001.

Figure 3.

SARS-CoV-2 neutralizing capacity of patients on hemodialysis and healthy controls after vaccination with BNT162b2. SARS-CoV-2 neutralizing capacity of vaccine-induced antibodies was determined by a virus neutralization test. Antibody-mediated inhibition of the SARS-CoV-2 receptor binding domain:angiotensin-converting enzyme 2 interaction is expressed as a percentage. Inhibition capacity of vaccine-induced antibodies in all and in age-matched healthy controls and patients on dialysis after the first (A and B) and after the second (C and D) COVID-19 vaccination. The dashed red lines represent the cutoffs for viral neutralization in this assay according to the manufacturer’s instructions. A cutoff of <30% binding inhibition indicates absence or a level of SARS-CoV-2 neutralizing antibodies below the limit of detection of this test. The number (N) of individuals exceeding the cutoff is expressed as a percentage. ***P<0.001.

Figure 4.

Age dependency of spike antigen–specific SARS-CoV-2 IgG levels and the neutralizing capacity of antibodies after vaccination with BNT162b2. Age-dependent courses of SARS-CoV-2 IgG antibodies and neutralizing antibodies after the first and after the second COVID-19 vaccinations in healthy controls (A) and patients on dialysis (B).