Humoral response after 3 doses of the BNT162b2 mRNA COVID-19 vaccine in patients on hemodialysis

To the editor:

Dialysis patients are at increased risk of severe coronavirus disease 2019 (COVID-19) infections.¹ Therefore, they are considered as being a priority population for COVID-19 vaccination. Because immune responses against vaccines are considerably reduced in this population,² a vaccination strategy including 3 doses of vaccine has been recommended for dialysis patients. However, few data exist concerning humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination with 3 doses of BNT162b2 (Pfizer–BioNTech) in patients on hemodialysis (HD). Moreover, about 90% of HD patients exhibit antibody positivity after 2 injections of vaccine,3, 4, 5, 6 and the relevance of a third dose is questionable. Nevertheless, only 75% exhibit robust responses after 2 doses, and a vaccine booster may be useful.⁷

We studied vaccine response in 50 HD patients who were COVID-19–naïve (no clinical history, negative serology) having received the BNT162b2 mRNA COVID-19 vaccine and 15 HD patients with a history of COVID-19 infections. Three doses of vaccine were proposed for naïve patients, and 2 were proposed for those previously exposed to COVID-19.

Forty-five naïve patients received 3 doses, whereas 5 received only 2 doses (refusal of patients). Humoral response was studied using the SARS-CoV-2 immunoassay, Abbott designed to detect IgG antibodies to the receptor-binding domain of the S1 subunit of the spike protein of SARS-CoV-2. As a relevant threshold cannot be determined, we used that provided by the manufacturer.

Among 45 naïve patients having received the 3 doses of vaccine, 40 (89%) had an antibody titer >50 arbitrary units [AU]/ml after 2 doses and 42 (93%) after 3 doses. Among the 5 nonresponders after 2 doses (antibody titer, <50 AU/ml), 2 had a robust response after the third dose (568 vs. 17 AU/ml and 923 vs. 35 AU/ml, respectively). Values of antibody titers were not normally distributed. Median values of antibody titers were 672 AU/ml (interquartile range [IQR]: 213–2528 AU/ml) and 6435 AU/ml (IQR: 2790–17,014 AU/ml) 1 month after the second and the third dose, respectively (Figure 1 ). After 3 doses, 92% of patients had antibody titers above the median antibody titer observed after 2 doses. Five patients denied a third dose of vaccine. There was no variation in antibody titers in 3 and a significant decline in 2.

Figure 1.

Antibody titers (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] immunoassay, which Abbott designed to detect IgG antibodies to the receptor-binding domain of the S1 subunit of the spike protein of SARS-CoV-2) before vaccine and after 2 and 3 doses of BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine. AU, arbitrary unit; S1, serology 1 = before vaccine; S2, serology 2 = after 2 doses; S3, serology 3 = after the third dose.

Median increase in antibody titers after the third dose was 580%. Explosive response (increase in titer >580%) was inversely related to antibody titer 1 month after the second dose (R ² = 0.373; P < 0.001). Those with an antibody titer <531 AU/ml after the second dose had better improvement in response (receiver operating curve characteristics, area under the curve, 0.77 [0.62–0.88]; P < 0.001; Figure 2 ).

Figure 2.

Receiver operating characteristic curve illustrating the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology after 2 doses of BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine to predict the increase in antibody titers after a third dose. Data in parentheses are interquartile range. AUC, area under the curve.

Antibody responses after 3 doses of vaccine in those not previously infected were similar to those after prior infection and 2 vaccine doses (5156 AU/ml [1502–21,569 AU/ml]).

We report in a single-center study that 90% of dialysis patients have a vaccine response after 2 doses of BNT162b2 mRNA COVID-19 vaccine. A third dose enhances humoral response in almost all patients (Figure 3 ), but especially in those with lower antibody titers after 2 doses. Moreover, a fraction of nonresponders after 2 doses develops a strong response after the third dose. Dialysis patients with low humoral response may benefit from a third dose of BNT162b2 mRNA COVID-19 vaccine.

Figure 3.

Individual variations in antibody titers (severe acute respiratory syndrome coronavirus 2 [SARS-Cov-2] immunoassay, which Abbott designed to detect IgG antibodies to the receptor-binding domain of the S1 subunit of the spike protein of SARS-CoV-2) during the vaccine scheme. AU, arbitrary unit.