Effect of Third and Fourth mRNA-Based Booster Vaccinations on SARS-CoV-2 Neutralizing Antibody Titer Formation, Risk Factors for Non-Response, and Outcome after SARS-CoV-2 Omicron Breakthrough Infections in Patients on Chronic Hemodialysis: A Prospective Multicenter Cohort Study

Abstract

The aim of this study is to determine the effect of repeated vaccinations on neutralizing SARS-CoV-2 IgG antibody titers, evaluate risk factors for immunological non-response, and to report breakthrough infections in chronic hemodialysis patients. Methods: A prospective, multi-center cohort study in 163 chronic hemodialysis patients was conducted. Antibody titers were measured three months after second, third, and fourth (10 pts) booster vaccinations. SARS-CoV-2 neutralizing antibody titers in BAU/mL and % inhibition were divided into three categories (<216, 216–433, >433 and <33, 33–66, and >66%). Somers’s test, paired t-test, and univariable and multivariable logistic regression analysis were applied to evaluate differences in antibody levels and search for risk factors for vaccination failure defined as neutralizing titers <50% and/or need for repeated booster vaccinations. Furthermore, we report on a case series to describe characteristics of patients after four vaccinations (n = 10) and breakthrough infections (n = 20). Results: Third dose boosters resulted in higher proportions of patients with neutralizing antibody levels >66% as compared to after the second dose (64.7% after second dose vs. 88.9% after third dose, p = 0.003), as well as in a respective increase in neutralizing titer levels in % from 68 ± 33% to 89 ± 24 (p < 0.001). The proportion of patients with IgG-titers below 216 BAU/mL decreased from 38.6 to 10.5% (p ≤ 0.001). Age (p = 0.004, OR 1.066, 95% CI 1.020–1.114) and presence of immunosuppressive medications (p = 0.002, OR 8.267, 95% CI 2.206–30.975) were identified as major risk factors for vaccination failure. Repeated booster vaccinations ≥4 times were effective in 8 out of 10 former low-responders (80%) without any side effects or safety concerns. Breakthrough infections showed a clinically mild course but were associated with prolonged viral shedding on PCR-testing ranging 7–29 (mean 13) days. Conclusions: Third and fourth mRNA-based booster vaccinations resulted in higher and longer lasting SARS-CoV-2 antibody levels as compared to after two dosages. The presence of immunosuppressive medication and repeat vaccinations are major potentially modifiable measures to increase antibody levels in non-or low-responders. Breakthrough infections with SARS-CoV-2 Omicron were associated with prolonged viral shedding but clinically mild disease courses.

Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients

“…Several studies report of superior immunity after initial mRNA-1273 prime/boost vaccination when compared to BNT162b2 in haemodialyis patients (30,31) or in the general population (32)(33)(34) and further improved humoral responses after triple vaccination in dialysis patients (35)(36)(37)(38)(39). Third dose vaccination with mRNA-1273 or BNT162b2 provided comparable protection against symptomatic SARS-CoV-2 infection in the general population, although differences between both vaccines were observed after the second dose (40).…”

Egyptian hemodialysis patients' willingness to receive the COVID-19 vaccine booster dose: a multicenter survey

“…Despite good public knowledge and awareness about COVID-19 severity and vaccine safety [ 22 ], hesitancy or refusal to take the vaccine has been present among a large portion of Egyptian citizens, even medical students [ 23 ] and healthcare workers [ 24 , 25 ]. Patients on maintenance HD have been shown to have diminished and waning humoral responses after COVID-19 vaccination [ 26 ], which improved after a third [ 27 ] or a fourth booster dose [ 28 ]. For Egyptian patients on maintenance HD, a previous study showed that about 40% of patients were hesitant or resistant to taking the COVID-19 vaccine [ 14 ].…”

Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients

“…Several studies report of superior immunity after initial mRNA-1273 prime/boost vaccination when compared to BNT162b2 in haemodialyis patients (28,29) or in the general population (30)(31)(32) and further improved humoral responses after triple vaccination in dialysis patients (33)(34)(35)(36)(37). Third dose vaccination with mRNA-1273 or BNT162b2 vaccines provided comparable protection against symptomatic SARS-CoV-2 infection in the general population although differences between both vaccines were observed after the second dose (38).…”