Humoral Response to One and Two Doses of ChAdOx1-S Vaccine in Patients on Hemodialysis

Compared with the healthy population, patients on hemodialysis (HD) are at greater risk of developing severe coronavirus disease 2019 (COVID-19) and dying once infected (¹). Effective vaccination is considered to be the way out of the COVID-19 pandemic. A number of studies have examined the immunogenicity of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients on HD. In a systematic review of 22 studies, 18%–53% and 70%–96% of patients on dialysis developed antibodies after one or two doses of the vaccine, respectively (²). Here we report the humoral immune response after one and two doses of the ChAdOx1-S vaccine in adult patients on HD and a comparator group of healthy controls.

Between May 1 and July 7, 2021, we recruited patients receiving HD at three facilities in Mohali and Panchkula, India, who had received one or two doses of ChAdOx1-S vaccine at least 14 days ago. Eligible patients were required to be on regular HD and clinically stable with no history of infection or hospitalization in the last 3 months. Patients were screened and tested for SARS-CoV-2 infection prior to dialysis according to local protocols, and those with documented infection were excluded. Healthy volunteers were recruited from among the members of the staff at the hospitals. All participants provided written informed consent.

Antibody against the S1 subunit of the SARS-CoV-2 spike protein antigen was measured using Elecsys Anti-SARS-CoV-2 S double antigen sandwich immunoassay. The detection range of this assay is 0.4–250 World Health Organization standardized binding antibody unit (BAU)/ml. Samples with high titer were diluted. As per the manufacturer, the assay sensitivity and specificity are 98.8% (95% confidence interval, 98.1% to 99.3%) and 99.98% (95% confidence interval, 99.91% to 100%), respectively, and a titer of ≥0.8 BAU/ml is considered reactive. Data are presented as median (25th, 75th percentile) for continuous variables and proportion for categorical variables.

We enrolled 85 participants, 53 and 32 of whom had received one and two doses of the ChAdOx1-S vaccine, respectively. A total of 59 healthy participants (45, one dose and 14, two doses) were also enrolled. The age of the patients on HD and healthy controls was a median of 62 years (25th and 75th percentile, 55, 66) and 37 years (25th and 75th percentile, 27, 43), respectively. A total of 33% of the healthy controls and 41% of those on HD were females. The median (interquartile range) time between the first dose and serology testing in HD patients and healthy controls, respectively, was 28 days (23, 40) and 49 days (36, 64) and between the second dose and serology testing was 20 days (9, 26) and 63 days (38, 72), respectively. In the fully vaccinated, the gap between the two doses was 39 days (32, 45) and 43 days (42, 47) for HD and healthy participants, respectively. Antibodies against SARS-CoV-2 spike protein were detected in 77% and 88% in the dialysis population and 98% and 100% in the control group after one and two doses, respectively (Figure 1). We did not find any association of antibody titers with age, sex, or comorbidities. However, compared with HD patients under the age of 60 years, those over that age had a numerically lower antibody response after one dose (234 [21, 6208] versus 21 [1, 236] BAU/ml) and two doses (2148 [198, 7094] versus 210.8 [2, 2618] BAU/ml), respectively.

Figure 1.: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibody level in healthy controls and patients on hemodialysis (HD) after one dose or two doses of the ChAdOx1-S vaccine. The median antibody titers (25th, 75th percentile) in the dialysis patients and healthy controls were 116 (2, 3887) BAU/ml and 113 (41, 3704) BAU/ml after one dose and 230 (41, 3337) BAU/ml and 630 (403, 1820) BAU/ml after two doses, respectively. Cutoff for reactive antibody is 0.80 BAU/ml, shown as a horizontal dotted black line. The lowest measurable value reported by the assay is 0.4 BAU/ml.

These data provide reassurance about the effectiveness of the ChAdOx1 vaccine in patients on HD and are of public health importance since ChAdOx1-S vaccine is one of the most widely used vaccines worldwide, second only to the BNT162b2 vaccine. The results were comparable with those reported by Billany et al. (³) (71% seroconversion) and Clarke et al. (unpublished observations) (83.5% seroconversion) after one dose and two doses of AZD1222/ChAdOx1-S vaccine, respectively, in patients on HD. The latter study showed similar seroconversion rates after BNT162b and ChAdOx1-S vaccines, but the antibody level was higher in those vaccinated with BNT162b (Clarke et al., unpublished observations).

There was greater heterogeneity in antibody response in the population on dialysis compared with the healthy controls. Monitoring of antibody levels might be advisable, especially in the older population and in those with comorbidities. Demonstration of antibody reactivity is not synonymous with immunity against infection and/or disease. However, anti-spike IgG levels correlate with neutralizing antibody titers. We did not examine the effect on T-cell mediated response, considered to be indicative of a longer-lasting immunity against viral infections. In a recent study (⁴), we showed that the mortality following COVID-19 infection was halved in patients on HD who had received even one vaccine dose.

Our study provides reassurance that inoculation with ChAdOx1 vaccine leads to generation of antibodies in a majority of patients on HD. The degree of protection against disease and its adverse outcomes afforded by the vaccination needs further study.

Disclosures

V. Jha has research grants from Baxter and GlaxoSmithKline and reports consultancy and advisory board honoraria from AstraZeneca and Baxter Healthcare, outside the published work. V. Jha also reports serving as a scientific advisor or member of NephroPlus.

All remaining authors have nothing to disclose.

Funding

None.