Evolution of SARS-CoV-2-Neutralizing Antibodies after Two Standard Dose Vaccinations, Risk Factors for Non-Response and Effect of a Third Dose Booster Vaccination in Non-Responders on Hemodialysis: A Prospective Multi-Centre Cohort Study

Abstract

The aim of this investigation was to determine the effect of SARS-Cov-2 vaccination in hemodialysis patients, search for risk factors for non- or low-response, and to measure the effect of a third booster vaccination in non- or low-responders. Methods SARS-CoV-2 IgG antibodies and the virus-neutralizing capacity were measured 4–5 weeks after a full standard vaccination in 95 chronic hemodialysis patients and 60 controls. IgG titers > 30 AU/mL served to classify participants as responders. Multivariable binary logistic regression analysis was used to search for risk factors of reduced vaccination success. Patients with vaccination failure were offered a third booster dosage. Results 82.1% of the patient cohort as compared to 98.3% of the healthy control group were able to mount SARS-CoV-2 titers above 30 AU/mL after two standard vaccine doses. Mean IgG antibody titers were lower in hemodialysis patients than controls (78 ± 35 vs. 90 ± 20 AU/mL, p = 0.002). Multivariable binary logistic regression analysis showed age and immunosuppressive medication as major risk factors for vaccination failure with a decreased probability of successful vaccination of −6.1% (95% CI −1.2 to −10.9) per increase in age of one year and −87.4% (95% CI −98.0 to −21.5) in patients on immunosuppressive therapy (crude odds ratio for vaccination failure for immunosuppressive therapy 6.4). Ten out of 17 patients with non-response to vaccination were offered a third dose. Booster vaccination after the second dose induced an increase in effective antibody titers of >30 AU/mL in seven out of ten patients 4–5 weeks later (70%). Conclusion Standard SARS-CoV-2 vaccination schemes are highly effective in mounting protective neutralizing IgG antibodies in chronic hemodialysis patients. Nevertheless, response to vaccination is diminished as compared to a healthy control group. Major risk factors for vaccination failure are older age and immunosuppressive therapy. In non- or low-responders to standard vaccination a third booster vaccination was able to induce effective antibody titers in about 70% of patients, indicating that a third booster vaccination might be preferable to decreasing immunosuppressive therapy.

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

“…On the contrary, we observed a positive correlation between the antibody titer after the second and third dose of the vaccine. Similar to the study of Dekervel et al [ 23 ], and in contrast to Tillmann’s findings [ 15 ], we did not show an age-response relationship to the third dose of the vaccine, which is commonly seen in the primary two-dose vaccination [ 9 , 26 , 27 ]. Primary vaccination non-responders did not react to a third vaccination in our study.…”

“…This study is one of the first on dialysis patients to show a significant increase in antibody titer after the third dose of the mRNA vaccine [ 14 , 15 , 23 ]. Although the antibody titer in infection-naïve dialysis subjects turned out to be lower than in the healthy and dialyzed convalescents, similar to what was observed earlier in the case of the primary cycle of vaccination [ 9 ], it was three times higher than after the second dose in the same group, and almost twice as high as in the control subjects after the second dose.…”

“…For example, Dekervel et al showed that the strength of the immune response to the third dose of an mRNA vaccine in hemodialyzed patients is similar to the response of healthy individuals to the two-dose primary vaccination [ 23 ]. Several studies have shown that the third dose of the vaccine produces a humoral response in half or most of the dialyzed patients who were not seroconverted after the two-dose primary vaccination [ 15 , 24 ]. Others demonstrated that patients with a poorer response to the primary vaccination had higher antibody production after the third dose than those with a higher antibody titer [ 14 , 25 ].…”

“…The sparse data on the waning of antibodies in the dialysis patient population shows inconsistent results [ 12 , 13 ]. The response to the third complementary dose of the mRNA vaccine, which is recommended on a regular schedule for immunocompromised individuals in many countries, appears to be very good [ 14 , 15 ]. To shed more light on these issues, we examined these topics in a controlled study of dialyzed patients and subjects without chronic kidney disease.…”

Decline of Humoral Responses 6 Months after Vaccination with BNT162b2 (Pfizer–BioNTech) in Patients on Hemodialysis

“…Numerous other studies confirmed these humoral response rates after vaccination. Between 77% [15] to 98% [16] of mRNA-vaccinated patients on hemodialysis showed antibody responses estimated by binding antibody titers [5,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] or neutralizing assays [15,22,26,34]. This is a markedly higher response rate compared to immunocompromised patients with hematological malignancies or solid organ transplant recipients, who have shown initial response rates around 20-85% [35][36][37].…”