Immunogenicity of COVID-19 Tozinameran Vaccination in Patients on Chronic Dialysis

Abstract

Patients with kidney failure have notoriously weak responses to common vaccines. Thus, immunogenicity of novel SARS-CoV-2 vaccines might be impaired in this group. To determine immunogenicity of SARS-CoV-2 vaccination in patients with chronic dialysis, we analyzed the humoral and T-cell response after two doses of mRNA vaccine Tozinameran (BNT162b2 BioNTech/Pfizer). This observational study included 43 patients on dialysis before vaccination with two doses of Tozinameran 21 days apart. Overall, 36 patients completed the observation period until three weeks after the second dose and 32 patients were further analyzed at week 10. Serum samples were analyzed by SARS-CoV-2 specific IgG and IgA antibodies ~1, ~3–4 and ~10 weeks after the second vaccination. In addition, SARS-CoV-2-specific T-cell responses were assessed at ~3–4 weeks by an interferon-gamma release assay (IGRA). Antibody and T cell outcomes at this timepoint were compared to a group of 44 elderly patients not on dialysis, after immunization with Tozinameran. Median age of patients on chronic dialysis was 74.0 years (IQR 66.0, 82.0). The proportion of males was higher (69.4%) than females. Only 20/36 patients (55.6%, 95%CI: 38.29–71.67) developed SARS-CoV-2-IgG antibodies at the first sampling, whereas 32/36 patients (88.9%, 95%CI: 73.00–96.38) demonstrated IgG detection at the second sampling. In a longitudinal follow-up at ~10 weeks after the second dose, the proportion of dialysis patients reactive for anti-SARS-CoV-2-IgG decreased to 27/32 (84.37%, 95%CI: 66.46–94.10) The proportion of anti-SARS-CoV-2 S1 IgA decreased from 33/36 (91.67%; 95%CI: 76.41–97.82) at weeks 3–4 down to 19/32 (59.38; 95%CI: 40.79–75.78). Compared to a cohort of vaccinees with similar age but not on chronic dialysis seroconversion rates and antibody titers were significantly lower. SARS-CoV-2-specific T-cell responses 3 weeks after second vaccination were detected in 21/31 vaccinated dialysis patients (67.7%, 95%CI: 48.53–82.68) compared to 42/44 (93.3%, 95%CI: 76.49–98.84) in controls of similar age. Patients on dialysis demonstrate a delayed, but robust immune response three to four weeks after the second dose, which indicates effective vaccination of this vulnerable group. However, the lower immunogenicity of Tozinameran in these patients needs further attention to develop potential countermeasures such as an additional booster vaccination.

Poor neutralization and rapid decay of antibodies to SARS-CoV-2 variants in vaccinated dialysis patients

“…The analysis of plasma SARS-CoV-2-specific IgG and IgA showed an overall response to mRNA vaccine in 94.4% dialysis patients, which is comparable to data shown in other reports (70.5-96%) 19,22,41,42 . Nevertheless, we observed reduced antibody levels after both the first and the second dose in HD patients who were naïve to SARS-CoV-2, a finding consistent with a delayed immune response in this population 19,43,44 .…”

Immunological and clinical efficacy of COVID-19 vaccines in immunocompromised populations: a systematic review

“…Thirty-three studies reported immunogenicity in 6302 patients on dialysis ( Table S4 ) [ [15] , [16] , [17] , 21 , 31 , 38 , 44 , [62] , [63] , [64] , 74 , 78 , 80 , [114] , [115] , [116] , [117] , [118] , [119] , [120] , [121] , [122] , [123] , [124] , [125] , [126] , [127] , [128] , [129] , [130] , [131] , [132] , [133] , [134] ]. Non-responder rates ranged from 2% to 30% ( Fig.…”

“…found a high non-response rate at 27% (22/80), at least partially explained by the choice of a higher cut-off (29 U/mL) than the one provided by the manufacturer of the serological assay [ 118 , 135 ]. Fifteen studies included a control group ( n = 779 overall), in which all but nine participants developed post-vaccine antibodies [ 17 , 21 , 63 , 74 , 78 , 80 , 116 , 118 , 120 , 121 , 124 , 126 , 128 , 131 , 134 ]. Speer et al.…”

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

“…So far, observational reports on SARS-CoV-2 vaccination in chronic hemodialysis patients have shown both, an insufficient immune response [ 11 , 12 ] as well as similar effectiveness when compared to the general population with reported effectiveness rates of >90% after a second dose [ 13 ]. Although the response rate of 82.1% in our multi-center cohort was significantly lower than in the healthy control group (98.3%), SARS-CoV-2 vaccination is by far more effective than the so far reported different other vaccinations e.g., for hepatitis B in this vulnerable patient cohort [ 14 ].…”