Impact of tozinameran (BNT162b2) mRNA vaccine on kidney transplant and chronic dialysis patients: 3-5 months followup

Abstract

Background: Determining the humoral immunogenicity of tozinameran (BNT162b2) vaccine in patients requiring chronic renal replacement therapy, and its impact on COVID-19 morbidity several months after vaccination, will guide risk assessment and subsequent changes in vaccination policy. Methods: In a prospective post-vaccination cohort study with up to 5 months follow-up we studied outpatient dialysis and kidney transplant patients and respective healthcare teams. Outcomes were anti S1/S2 antibody response to vaccine or infection and infection rate during followup. Results: 175 dialysis patients (40% women, 65+/-15 years), 252 kidney transplant patients (33% women, 54+/-14 years) and 71 controls (65% women, 44+/-14 years) were followed. Three months or longer after vaccination we detected anti S1/S2 IgG antibodies in 80% of dialysis patients, 44% of transplant recipients and 100% of controls, whereas respective rates after infection were 94%, 75% and 100%. Predictors of non-response were age, diabetes, history of cancer, lower lymphocyte count and lower vitamin-D levels. Factors associated with lower titers in dialysis patients were modality (hemodialysis vs peritoneal) and serum ferritin levels. In transplant patients, hypertension and higher calcineurin or mTOR inhibitor drug levels were linked with diminished antibody response. Vaccination associated with fewer subsequent infections (HR=0.23, p<0.05). Moreover, higher antibody titers associated with fewer events, HR 0.41 for each unit increased in log10titer (p<0.05). Conclusions: Dialysis patients, and more so kidney transplant recipients, mounted delayed and reduced antibody response to COVID-19 mRNA vaccination, and lesser humoral response associated with more infections. Measures to identify and protect non-responsive patients are urgently required.

Response to Tozinameran (BNT162b2) booster in twice-vaccinated kidney transplant and maintenance dialysis patients

“…We have previously noted that with a most recent antibody level at or above 59 AU/ml no post-vaccination cohort participant became infected with COVID-19, suggesting a protective cutoff 5 . Figure 2b shows that prior to boosting, this level was achieved by 80% of controls, 35% of dialysis patients and 10% of transplant patients, while 8-54 days after booster injection respective rates were 100%, 93% and 58%.…”

“…Patients needing chronic renal replacement therapy are at risk for severe COVID-19 3 and have been shown to mount a lesser humoral response to mRNA vaccination 4 . In our single center cohort we have observed that reduced vaccine-elicited antibody levels in dialysis and kidney transplant patients associated with increased infection rates 5 . Herein, we describe the short term impact of booster administration in these patients, amidst a third wave of infections and deaths currently experienced in Israel primarily by the Delta variant, possibly amplified by waning immunity ( Figure 1 ) 6 .…”

“…Prior to initiation of vaccination we launched the COVID-19 mRNA Vaccine Immunogenicity in patients with end stage Renal Disease (COVIReD) prospective cohort study designed to investigate the long-term kinetics and implications of antibody response to COVID-19 vaccine and infection in this vulnerable population. Its methods and preliminary results have been recently published 5 . In this update, we report patients’ humoral responses to booster vaccination.…”

Response to tozinameran (BNT162b2) booster in twice-vaccinated kidney transplant and maintenance dialysis patients

“…Patients needing chronic renal replacement therapy are at risk for severe COVID-19 and have been shown to mount a lesser humoral response to mRNA vaccination [ 2 ]. In our single-center cohort we observed that reduced vaccine-elicited antibody levels in dialysis and kidney transplant patients were associated with increased infection rates [ 3 ]. Herein, we describe the short-term impact of booster administration in these patients, amidst a third wave of infections and deaths currently experienced in Israel primarily by the Delta variant, possibly amplified by waning immunity (Online Resource 1).…”

“…Prior to initiation of vaccination we launched the COVID-19 mRNA Vaccine Immunogenicity in patients with end stage Renal Disease (COVIReD) prospective cohort study designed to investigate the long-term kinetics and implications of antibody response to COVID-19 vaccine and infection in this vulnerable population. The study was approved by the local ethical Committee and its methods and preliminary results have been recently published [ 3 ]. In this update, we report patients’ humoral responses to booster vaccination.…”