Abstract
Hemodialysis patients are at high risk for severe COVID-19, and impaired seroconversion rates have been demonstrated after COVID-19 vaccination. Humoral immunity wanes over time and variants of concern with immune escape are posing an increasing threat. Little is known about protection against the B.1.617.2 (delta) variant of concern in hemodialysis patients before and after third vaccination. We determined anti-S1 IgG, surrogate neutralizing, and IgG antibodies against different SARS-CoV-2 epitopes in 84 hemodialysis patients directly before and three weeks after a third vaccine dose with BNT162b2. Third vaccination was performed after a median (IQR) of 119 (109–165) days after second vaccination. In addition, neutralizing activity against the B.1.617.2 (delta) variant was assessed in 31 seroconverted hemodialysis patients before and after third vaccination. Triple seropositivity for anti-S1 IgG, surrogate neutralizing, and anti-RBD antibodies increased from 31/84 (37%) dialysis patients after second to 80/84 (95%) after third vaccination. Neutralizing activity against the B.1.617.2 (delta) variant was significantly higher after third vaccination with a median (IQR) ID50 of 1:320 (1:160–1:1280) compared with 1:20 (0–1:40) before a third vaccine dose (P<0.001). The anti-S1 IgG index showed the strongest correlation with the ID50 against the B.1.617.2 (delta) variant determined by live virus neutralization (r=0.91). We demonstrate low neutralizing activity against the B.1.617.2 (delta) variant in dialysis patients four months after standard two-dose vaccination but a substantial increase after a third vaccine dose. Booster vaccination(s) should be considered earlier than 6 months after the second vaccine dose in immunocompromised individuals.
Highlights
The current coronavirus disease 2019 (COVID-19) pandemic has led to more than 270 million cases and around 5.3 million deaths worldwide as of December 2021 [1]
Vulnerable cohorts such as hemodialysis patients were prioritized for a third mRNA vaccine dose
We demonstrate a significant increase for each, anti-S1 IgG, surrogate neutralizing, and 4 different SARS-CoV-2 anti-spike antibodies in hemodialysis patients with the administration of a third vaccine dose
Summary
The current coronavirus disease 2019 (COVID-19) pandemic has led to more than 270 million cases and around 5.3 million deaths worldwide as of December 2021 [1]. COVID-19 vaccination has been proven safe and effective in preventing severe COVID-19 disease with more than 8 billion vaccine doses already administered globally [1]. Hemodialysis patients are still at great risk for severe COVID-19 because of advanced age, underlying comorbidities, and premature aging of the immune system resulting in lower humoral and cellular vaccine response [2, 3]. First real-world data investigated the effectiveness of mRNA vaccination in 12,169 hemodialysis patients: vaccinated hemodialysis patients had a lower risk of COVID-19 infection as well as a significantly lower incidence of hospitalization or death compared with unvaccinated patients [6]. Waning humoral immunity has been demonstrated in healthy and dialysis populations as early as three months after second vaccine dose, leading to an increase in breakthrough-infections [7–9]
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