Background and objectives Patients receiving hemodialysis are at high risk for both SARS-CoV-2 infection and severe COVID-19 disease. A life-saving vaccine is available, but sensitivity to vaccines is generally lower in dialysis patients. Little is yet known about antibody responses after COVID-19 vaccination in this vulnerable group. Design, setting, participants, and measurements In this prospective single-center study, we included 22 dialysis patients 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 >1, neutralizing antibodies with a threshold for viral neutralization of ≥30% and antibodies against different SARS-CoV-2 fragments 17-22 days after the first and 18-22 days after the second dose of the mRNA vaccine BNT162b2. Results After the first vaccine dose, 4/22 (18%) dialysis patients compared with 43/46 (93%) healthy controls developed positive anti-S1 IgG, with a median (IQR) anti-S1 IgG index of 0.2 (0.1-0.7) compared with 9 (4-16), respectively. SARS-CoV-2 neutralizing antibodies exceeded the threshold for neutralization in 4/22 (18%) dialysis patients compared with 43/46 (93%) in healthy controls, with a median (IQR) percent inhibition of 11 (3-24) compared with 65 (49-75), respectively. After the second dose, 14/17 (82%) of dialysis patients developed neutralizing antibodies exceeding the threshold for viral neutralization and antibodies against the receptor-binding S1-domain of the spike protein, compared to 46/46 (100%) of healthy controls, respectively. The median (IQR) percent inhibition was 51 (32-86) compared to 98 (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.

Three reports address the protection of the vulnerable population of patients with hematologic malignancies in the face of the ongoing COVID pandemic. The reports suggest that some patients who fail to mount a B-cell response to vaccine may nevertheless have protective T cell responses. As a group, these reports suggest that patients should continue to be immunized with additional doses to attempt to improve immune response but that they need to maintain the precautions recommended for the unvaccinated.

Despite limited data on safety and immunogenicity, heterologous prime-boost vaccination is currently recommended for individuals with ChAdOx1 nCoV-19 prime immunization in certain age groups. In this prospective, single-center study we included 166 health care workers from Heidelberg University Hospital who received either heterologous ChAdOx1 nCoV-19/BNT162b2, homologous BNT162b2 or homologous ChAdOx1 nCoV-19 vaccination between December 2020 and May 2021. We measured anti-S1 IgG, SARS-CoV-2 specific neutralizing antibodies, and antibodies against different SARS-CoV-2 fragments 0–3 days before and 19–21 days after boost vaccination. Before boost, 55/70 (79%) ChAdOx1 nCoV-19-primed compared with 44/45 (98%) BNT162b2-primed individuals showed positive anti-S1 IgG with a median (IQR) anti-S1 IgG index of 1.95 (1.05–2.99) compared to 9.38 (6.26–17.12). SARS-CoV-2 neutralizing antibodies exceeded the threshold in 24/70 (34%) of ChAdOx1 nCoV-19-primed and 43/45 (96%) of BNT162b2-primed individuals. After boosting dose, median (IQR) anti-S1 IgG index in heterologous ChAdOx1 nCoV-19/BNT162b2 vaccinees was 116.2 (61.84–170), compared to 13.09 (7.03–29.02) in homologous ChAdOx1 nCoV-19 and 145.5 (100–291.1) in homologous BNT162b2 vaccinees. All boosted vaccinees exceeded the threshold for neutralization, irrespective of their vaccination scheme. Vaccination was well-tolerated overall. We show that heterologous ChAdOx1 nCoV-19/BNT162b2 vaccination is safe and induces a strong and broad humoral response in healthy individuals.

Seroconversion after COVID‐19 vaccination is impaired in kidney transplant recipients. Emerging variants of concern such as the B.1.617.2 (delta) and the B.1.1.529 (omicron) variants pose an increasing threat to these patients. In this observational cohort study, we measured anti‐S1 IgG, surrogate neutralizing, and anti‐receptor‐binding domain antibodies three weeks after a third mRNA vaccine dose in 49 kidney transplant recipients and compared results to 25 age‐matched healthy controls. In addition, vaccine‐induced neutralization of SARS‐CoV‐2 wild‐type, the B.1.617.2 (delta), and the B.1.1.529 (omicron) variants was assessed using a live‐virus assay. After a third vaccine dose, anti‐S1 IgG, surrogate neutralizing, and anti‐receptor‐binding domain antibodies were significantly lower in kidney transplant recipients compared to healthy controls. Only 29/49 (59%) sera of kidney transplant recipients contained neutralizing antibodies against the SARS‐CoV‐2 wild‐type or the B.1.617.2 (delta) variant and neutralization titers were significantly reduced compared to healthy controls ( p < 0.001). Vaccine‐induced cross‐neutralization of the B.1.1.529 (omicron) variants was detectable in 15/35 (43%) kidney transplant recipients with seropositivity for anti‐S1 IgG, surrogate neutralizing, and/or anti‐RBD antibodies. Neutralization of the B.1.1.529 (omicron) variants was significantly reduced compared to neutralization of SARS‐CoV‐2 wild‐type or the B.1.617.2 (delta) variant for both, kidney transplant recipients and healthy controls ( p < .001 for all).

Background and objectivesAntibody response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is impaired in kidney transplant recipients. Emerging variants, such as B.1.617.2 (δ), are of particular concern because of their higher transmissibility and partial immune escape. Little is known about protection against these variants in immunocompromised patients.Design, setting, participants, & measurementsIn this prospective two-center study, antispike 1 IgG and surrogate neutralizing antibodies were measured in 173 kidney transplant recipients and 166 healthy controls with different vaccination schedules. In addition, different SARS-CoV-2 epitope antibodies from 135 vaccinated kidney transplant recipients were compared with antibodies in 25 matched healthy controls after second vaccination. In 36 kidney transplant recipients with seroconversion, neutralization against B.1.1.7 (α), B.1.351 (β), and B.1.617.2 (δ) was determined on VeroE6 cells and compared with neutralization in 25 healthy controls.ResultsKidney transplant recipients had significantly lower seroconversion rates compared with healthy controls. After the second vaccination, antispike 1, antireceptor-binding domain, and surrogate neutralizing antibodies were detectable in 30%, 27%, and 24% of kidney transplant recipients, respectively. This compares with 100%, 96%, and 100% in healthy controls, respectively (P<0.001). Neutralization against B.1.1.7 was detectable in all kidney transplant recipients with seroconversion, with a median serum dilution that reduces infection of cells by 50% of 80 (interquartile range, 80–320). In contrast, only 23 of 36 (64%) and 24 of 36 (67%) kidney transplant recipients showed neutralization against B.1.351 and B.1.617.2, respectively, with median serum dilutions that reduce infection of cells by 50% of 20 (interquartile range, 0–40) and 20 (interquartile range, 0–40), respectively. Neutralization against different variants was significantly higher in healthy controls (P<0.001), with all patients showing neutralization against all tested variants.ConclusionsSeroconverted kidney transplant recipients show impaired neutralization against emerging variants of concern after standard two-dose vaccination.Clinical Trial registry name and registration number:Observational study to assess the SARS-CoV-2 specific immune response in kidney transplant recipients (COVID-19 related immune response), DRKS00024668

It has been demonstrated that patients on hemo- or peritoneal dialysis are particularly susceptible to SARS-CoV-2 infection and impaired seroconversion compared to healthy controls. Follow-up data on vaccination response in dialysis patients is limited but is greatly needed to individualize and guide (booster) vaccination strategies. In this prospective, multicenter study we measured anti-spike S1 and neutralizing antibodies in 124 hemodialysis patients, 41 peritoneal dialysis patients, and 20 age- and sex-matched healthy controls over 12 weeks after homologous BNT162b2 vaccination. Compared to healthy controls, both hemodialysis and peritoneal dialysis patients had lower anti-S1 IgG antibodies (median (IQR) 7.0 (2.8–24.3) and 21.8 (5.8–103.9) versus 134.9 (23.8–283.6), respectively; p < 0.001 and p < 0.05) and a reduced SARS-CoV-2 spike protein–ACE2 binding inhibition caused by vaccine-induced antibodies (median (IQR) 56% (40–81) and 77% (52–89) versus 96% (90–98), respectively; p < 0.001 and p < 0.01) three weeks after the second vaccination. Twelve weeks after the second vaccination, the spike protein–ACE2 binding inhibition significantly decreased to a median (IQR) of 45% (31–60) in hemodialysis patients and 55% (36–78) in peritoneal dialysis patients, respectively (p < 0.001 and p < 0.05). Peritoneal dialysis patients mounted higher antibody levels compared with hemodialysis patients at all time points during the 12-week follow-up. Individual booster vaccinations in high-risk individuals without seroconversion or rapidly waning neutralizing antibody levels are required and further data on the neutralization of emerging variants of concern in these patients are urgently needed.

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Figure 1 Humoral responses after a third COVID-19 vaccine dose with BNT162b2 in patients with ANCA-associated vasculitis (AAV) on maintenance therapy. (A) SARS-CoV-2 anti-S1 IgG and surrogate neutralising antibody levels were measured after the second COVID-19 vaccine dose (N=21 and N=16), immediately before a third vaccine dose with BNT162b2 (N=16) and after third vaccination (N=21) in patients with AAV on maintenance therapy. Anti-S1 IgG antibody levels are shown logarithmically as an anti-S1-IgG index. The dashed red line represents the cut-off for detection. A semiquantitative index of ≥1 was classified as positive. Surrogate neutralising antibodies are given as per cent binding inhibition. A cut-off of <30% binding inhibition (dashed red line) indicates the cut-off for detection of this assay. (B) Titers of neutralising antibodies against the B.1.617.2 (delta) variant were determined in a live virus SARS-CoV-2 infection assay using VeroE6 target cells and serial twofold serum dilutions after the second (N=16), directly before a third (N=16) and after (N=21) a third vaccine dose with BNT162b2. Neutralisation titers refer to the serum dilution that inhibits 50% of the infectivity (ID 50 ). The results of the three different time points in (A) and (B) were compared using Friedman's test for paired samples with Dunn's post-test. (C) Humoral responses of patients with AAV who had received a rituximab (monoclonal anti-CD20 antibody) dose <1 year before third COVID-19 vaccination (N=8) were analysed separately with the Mann-Whitney U test. (D) The correlation between the anti-S1-IgG index or the surrogate neutralisation assay and the neutralisation of B.1.617.2 (delta) was examined in patients with AAV using Spearman's correlation analysis, respectively. ANCA, antineutrophil cytoplasmic antibodies; RTX, rituximab; sVNT, surrogate neutralisation antibodies; *p<0.05; **p<0.01; ***p<0.001.