SARS‐CoV‐2 booster effect and waning immunity in hemodialysis patients: A cohort study

Patients with end‐stage kidney disease on dialysis suffer high morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Despite successful vaccination campaigns by dialysis providers, the standard two‐dose vaccination series with Pfizer BioNTech (BNT162b2) messenger RNA (mRNA) SARS‐ CoV‐2 is insufficient to protect patients from infection due to Omicron variants. Current guidelines recommend boosters of SARS‐ CoV‐2 mRNA‐based vaccines. However, data regarding humoral response post‐booster is limited in dialysis patients. Additionally, few studies directly compare the long‐term response after two doses of a coronavirus disease 2019 (COVID‐19) vaccine to the response after three doses in the same cohort of patients. Studies suggest that the third dose of BNT162b2 increases antibody levels in dialysis patients. However, antibody response and booster effectiveness are diminished in dialysis patients compared with the general healthy population. We previously reported long‐term humoral responses to two doses of BNT162b2 in a cohort of hemodialysis patients. Six months after full vaccination, 40% of patients' anti‐spike protein IgG levels were either undetectable or borderline. Here, we report responses to the first booster of the BNT162b2 vaccine in these patients.


| INTRODUCTION
Patients with end-stage kidney disease on dialysis suffer high morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite successful vaccination campaigns by dialysis providers, the standard two-dose vaccination series with Pfizer BioNTech (BNT162b2) messenger RNA (mRNA) SARS-CoV-2 is insufficient to protect patients from infection due to Omicron variants. 1 Current guidelines recommend boosters of SARS-CoV-2 mRNA-based vaccines. 2 However, data regarding humoral response post-booster is limited in dialysis patients. Additionally, few studies directly compare the long-term response after two doses of a coronavirus disease 2019 (COVID-19) vaccine to the response after three doses in the same cohort of patients. Studies suggest that the third dose of BNT162b2 increases antibody levels in dialysis patients. 3 However, antibody response and booster effectiveness are diminished in dialysis patients compared with the general healthy population. 4 We previously reported long-term humoral responses to two doses of BNT162b2 in a cohort of hemodialysis patients. 5 Six months after full vaccination, 40% of patients' anti-spike protein IgG levels were either undetectable or borderline. Here, we report responses to the first booster of the BNT162b2 vaccine in these patients.

| METHODS
We performed a prospective cohort study measuring serial semiquantitative IgG antibodies to the SARS-CoV-2 spike protein S1 receptor binding domain. We evaluated the response at a mean of 2, 6, and 11 weeks post-booster. The Anti-SARS-CoV-2 QuantiVac ELISA (IgG) from Euroimmun (EUROIMMUN US, Inc.) was used in all assessments. Final results were reported in WHO-recommended binding antibody units (BAU/ml) per the manufacturer's instructions. 6 Final results were considered negative for <25.6 BAU/ml, borderline for 25.6 to <35.2 BAU/ml, and positive for ≥35.2 BAU/ml. Clinical data were obtained as previously described. 5 Of 35 hemodialysis patients in the original cohort, 27 (77.1%) received a third dose of BNT162b2, and 20/27 (74%) had complete data (4-time point measurements): pre-booster (mean of 6 weeks pre-booster) and 2, 6, and 11 weeks post-booster. Two weeks was used to attain peak/initial antibody levels. 7  wileyonlinelibrary.com/journal/hsr2 vaccination. 5 Encouragingly, a third dose appears to restore antibodies to high levels, though these waned quickly in the ensuing weeks. Similar trends of antibody decline are seen in healthy individuals, although dialysis patients may differ from the general population with reduced peak levels and lower seroconversion rates. 8,9 Long-term durability remains unclear and protective levels against infection are unknown. Goldblatt et al. 10 reported that the mean protective threshold against WT SARS-CoV-2 virus was 154 BAU/ml (95% CI 42-559) but higher levels are presumed to be required against current variants.
Interestingly, previously infected patients saw a blunted rise in antibody level after an initial booster shot, though these patients started from a higher baseline. Thus, overall, they attained similar peak levels. While our sample size precludes further analysis of this finding, the interaction of natural immunity with booster vaccination response in dialysis patients requires further study.
During the recent Omicron wave, boosters were found to be protective from hospitalization and severe illness in the general population, however, this effect was time-dependent and declined significantly at 4 months post-booster. 11 A similar pattern is likely in patients on dialysis, but few studies have been conducted in this population. In one study, 93% of dialysis patients who received the third dose of BNT162b2 vaccine achieved antibody levels associated with protection, compared with only 35% pre-booster. 12 The Centers for Disease Control recommends a fourth dose of mRNA vaccines for select populations. 2 The utility of such a strategy in dialysis patients remains unclear but the humoral antibody waning seen in dialysis populations may support additional boosters.
Our study has limitations: small sample size, brief follow-up time and focus on humoral immunity. In conclusion, our data illustrate that, although humoral immunity wanes, patients on hemodialysis demonstrate strong antibody responses to a third dose of the BNT162b2 vaccine.

CONFLICT OF INTEREST
The authors declare no conflict of interest.

DATA AVAILABILITY STATEMENT
The data set used for this analysis is not publicly available. The data utilized was obtained from the Electronic Health Record and from the dialysis-specific electronic medical record system, which is restricted to use by only authorized employees.