Long-term trajectories of SARS-CoV-2 neutralizing antibodies and predictive value of first dose vaccination-induced IgG-antibodies in hemodialysis patients

Abstract

Purpose The predictive value of antibody titers after the first SARS-CoV-2 vaccination and long-term trajectories of antibody titers in hemodialysis patients are unknown. Methods SARS-CoV-2 IgG antibodies and their neutralizing effect six weeks after the first and second vaccination were analysed in 30 hemodialysis patients. IgG titers served to classify participants as responders or non-responders and to calculate sensitivity, specificity, and accuracy. Associations between potential risk factors and post-vaccine non-response were analysed by Mann–Whitney-U test and Chi-Squared test. Long-term follow-up analysis (ANOVA) on the evolution of neutralizing IgG-titers was performed in 24 participants 94 and 135 days after the second immunization. Results IgG antibodies ≥ 1 AU/L (mean 9 ± 20 AU/L) after the first dose were found in 20 patients (66.7%). After the second dose only two participants (6.7%) remained sero-negative and 16.6% showed neutralizing levels below 30%, whereas 25 patients showed IgG antibodies with the high neutralizing activity of 86 ± 18%. Positive IgG antibodies 6 weeks after the first vaccination predicted vaccination effectiveness after two cycles with a specificity of 100%, sensitivity of 76%, and accuracy of 87%. Even low-dose immunosuppressive therapy increased the relative risk for non-response after the first and second dose 1.9 (95% CI 0.8–4.6) and 4.9 (95% CI 1.0–23.8) times, respectively. Over a period of about 4.5 months IgG titers slowly declined by 51% from baseline or by 0.45 AU/mL per day, respectively. Conclusion Two cycles of SARS-CoV-2 vaccination-induced high seroconversion rates comparable to the general population. Immunosuppressive medication is a major risk factor for vaccination non-response. Mounted IgG antibodies showed a high neutralizing capacity as evidence of protective effectiveness. IgG antibodies after the first dose may serve to predict later vaccination outcome. Patients on dialysis display a more rapid decline in antibody titers on long-term follow-up compared to healthy controls.

Waning Humoral Response after COVID-19 mRNA Vaccination in Maintenance Dialysis Patients and Recovery after a Complementary Third Dose

“…However, the kinetics of antibody waning after vaccination is poorly understood in this group of patients. A few studies indicate a faster decline in the neutralizing antibody titer in dialysis patients than in the general population [ 20 ]. It is not fully known what vaccination schedule against COVID-19 is optimal for dialysis patients, and at what number of doses and in what intervals it should be administered.…”

SARS-CoV-2 spike protein antibody titers 6 months after SARS-CoV-2 mRNA vaccination among patients undergoing hemodialysis in Japan

“…With respect to long-term humoral immunity after vaccination, several studies among health care workers have reported that SARS-CoV-2 spike protein antibody titers and neutralizing antibodies progressively decline up to 6 months after vaccination [ 3 , 4 , 37 , 38 ]. Studies of HD patients in Germany showed that SARS-CoV-2 spike protein antibody titers peaked 1 month after the second vaccination in dialysis patients and declined to approximately 50% of peak values 3–4 months later [ 5 , 23 , 39 ]. The results of the present study showed that 6 months after the second dose of the BNT162b2 vaccine, SARS-CoV-2 spike protein antibody titers were markedly decreased (approximately one-seventh) compared with the peak value 1 month after vaccination.…”

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

“…Therefore, we cannot comment on titer evolution in patients with third booster vaccinations who already had titers higher than 433 BAU/mL after the second dose. Nevertheless, one might speculate that repeat vaccinations may result in decreased waning of antibody titers as described in different other patient populations [ 25 ] and dialysis patients [ 26 , 27 ]. Despite rapid titer waning, Clarke et al were able to confirm a longstanding SARS-CoV-2 antigen–specific T-cell response in patients without detectable antibody titers six months post vaccination [ 28 ].…”