Introduction
A third dose of SARS-CoV-2 mRNA vaccine has been administered in several countries.1,2 Patients with end-stage kidney disease have a weak immune response to 2-sessional doses of the mRNA vaccine.3, 4, 5, 6, 7 Because patients undergoing hemodialysis (HD) are at a high risk for COVID-19 severity and death, they have been prioritized in vaccination programs worldwide.8,9

To the best of our knowledge, there are no reports comparing humoral immunity after the third vaccination in hundreds of patients undergoing HD with that of healthy controls. However, the existing studies are limited by their small sample size. Therefore, in this multi-institutional retrospective study, we examined the impact of the BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine third dose on anti-SARS-CoV-2 spike protein S1 IgG antibody (anti-S IgG) titers in patients on HD and health care workers (HCWs).

Results
The final analyses included 350 patients on HD and 130 HCWs (Supplementary Table S1). After the second vaccination, the patients undergoing HD had significantly lower anti-S IgG titers than the HCWs with a median of 2538.8 (interquartile range [IQR]: 1185.6–4938.1) AU/ml versus 7645.1 (IQR: 4856.8–11,000) AU/ml 1 month after the second dose (P < 0.001); and 312.8 (IQR: 157.9–613.6) versus 803.8 (IQR: 498.4–1342.7) AU/ml at 6 months after the second dose (P < 0.001), respectively (Supplementary Table S2). Nevertheless, the increased titers 1 month after the third dose were comparable in both groups with a median of 24,500 (IQR: 11,000–40,000) AU/ml in the patients on HD versus 20,000 (IQR: 12,750–32,250) AU/ml in the HCWs. Similarly, the log-transformed anti-S IgG level in the HD group was significantly lower than that in the HCWs from 1 to 6 months after the second vaccination (Figure 1). The third dose of BNT162b2 increased anti-S IgG titers of the patients undergoing HD toward the same level as that of the HCWs with a mean of 9.94 (95% confidence interval: 9.84–10.05) log (AU/ml) in the HD group versus 9.94 (95% confidence interval: 9.82–10.07) in the HCW group (Figure 1). Although the seronegativity rate at 6 months after the second dose was significantly higher in the HD group (7.7%, n = 27) than that in the HCW group (0%, n = 0; P < 0.001), the seronegativity rates at 1 month after the third dose were 0% in both groups (Supplementary Table S3). The rate of high responders was 48 of 350 (13.7%) in the HD group versus 73 of 130 (56.2%) in the HCW group at 1 month after the second dose and 306 of 350 (87.4%) versus 125 of 130 (96.2%) 1 month after the third dose (Supplementary Tables S4 and S5). In addition, after the third dose, no responders or low responders had a significant increase in anti-S IgG titers compared with that in high responders with a 90.8-fold (IQR: 27.5–174.1) increase in no responders, a 10.2-fold (IQR: 5.7–19.2) increase in low responders, and a 3.3-fold (IQR: 2.4–6.1) increase in high responders (Figure 2a). Similarly, after the third dose in the HCW group, a greater fold increase in anti-S IgG titers was observed in low responders than that in high responders (3.7-fold [IQR: 2.7–6.0] vs. 2.0-fold [IQR: 1.4–3.5]; P < 0.001; Figure 2b).