Local and Systemic Immunity Are Impaired in End-Stage-Renal-Disease Patients Treated With Hemodialysis, Peritoneal Dialysis and Kidney Transplant Recipients Immunized With BNT162b2 Pfizer-BioNTech SARS-CoV-2 Vaccine.

Vaccination against COVID-19 in patients with end-stage renal disease (ESRD) on replacement therapy and kidney transplant recipients (KTRs) is particularly important due to the high mortality rate. Here, we tested the local and systemic immunity to the novel Pfizer BioNTech (BNT162b2) messenger RNA (mRNA) in ESRD, KTR patients, and healthy individuals (150 subjects). The ESRD group was divided into: hemodialysis (HD) and peritoneal dialysis (PD). We investigated the local and systemic immunity based on anti-N (nucleoprotein) and anti-S (spike1/2) Immunoglobulin A (IgA) and Immunoglobulin G (IgG) antibodies, respectively. Additionally, we performed an Interferon gamma (IFN-γ) release test Interferon-gamma release assay (IGRA) to monitor the cellular component of vaccine response. The control group had the highest level of anti-S IgG antibodies (153/2,080 binding antibody units (BAU)/ml) among all analyzed patients after the 1st and 2nd dose, respectively. The HD group (48/926 BAU/ml) had a diminished antibody level compared to PD (93/1,607 BAU/ml). Moreover, the seroconversion rate after the 1st dose was lower in HD than PD (56% vs. 86%). KTRs had extremely low seroconversion (33%). IgA-mediated immunity was the most effective in the control group, while other patients had diminished IgA production. We observed a lower percentage of vaccine responders based on the IFN-γ level in all research participants (100% vs. 85% in control, 100% vs. 80% in PD, 97% vs. 64% in HD). 63% of seropositive KTRs had a positive IGRA, while 28% of seronegative patients produced IFN-γ. Collectively, PD patients had the strongest response among ESRD patients. Two doses of the Pfizer vaccine are ineffective, especially in HD and KTRs. A closer investigation of ESRD and KTRs is required to set the COVID-19 vaccine clinical guidance. Clinical Trial Registration Number: www.ClinicalTrials.gov, identifier: NCT04 905 862.

Safety and Tolerability of mRNA COVID-19 Vaccines in Kidney Transplant Recipients.

BACKGROUND: COVID-19 mRNA vaccines have demonstrated excellent short-term safety in phase 3 trials. However, no kidney transplant recipients (KTR) were included. The aim of the study was to assess the safety and tolerability of COVID-19 mRNA vaccines in KTR. MATERIALS AND METHODS: A longitudinal controlled study was conducted in 300 KTR and 143 control patients (CRL) without chronic kidney disease who had received 2-dose vaccinations with the mRNA vaccine. Solicited local and systemic reactogenicity and unsolicited adverse events were assessed with a standardized questionnaire. The toxicity grading scales were derived from the FDA guidelines. RESULTS: KTR (62.7% men) with a median (interquartile range) age of 53 (41-63) and transplant vintage of 7.25 (3-13) years did not differ with respect to age and sex distribution from CRL. One hundred percent CRL and 83.3% KTR were vaccinated with BNT162b2 (BionTech/Pfizer); 16.7% KTR received mRNA-1273 (Moderna) vaccine. Any local reactions were present in 84.7% (first dose) and 65.3% (second dose) KTR vs 67.1% and 60.1% CRL within 7 days after the vaccination. Any systemic reactions were reported by 26.7% (first dose) and 20.9% (second dose) KTR vs 24.7 and 35.7% CRL. The most common systemic reactions in KTR were fatigue, headache and myalgia. No serious adverse events were observed. Many systemic reactions were observed less frequently in KTR than CRL. Younger KTR (<54 years) reported any local and any systemic reactions significantly more frequently than older patients. CONCLUSION: mRNA COVID-19 vaccines are safe and well-tolerated by KTR. The results may resolve patients' doubts and reduce their vaccine hesitancy.

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

The aim of this study was to analyze the waning of anti-spike (S) antibodies after mRNA vaccination against COVID-19 in maintenance dialysis patients, and to assess the safety and effectiveness of the complementary third dose. This was a prospective, longitudinal study in which we analyzed the kinetics of antibodies up to six months after a two-dose vaccination (first protocol) in infection-naïve dialysis patients (IN-Ds), previously infected dialysis patients (PI-Ds) and subjects without chronic kidney disease (the controls), as well as their humoral response to the third dose of the same mRNA vaccine (second protocol). The respective reduction in antibody titer after 3 and 6 months by 82.9% and 93.03% in IN-Ds (n = 109), 73.4% and 93.36% in PI-Ds (n = 32) and 75.5% and 88.8% in the controls (n = 20) was demonstrated. Consequently, a protective antibody titer above 141 BAU/mL was found in only 47.7% and 23.8% of IN-Ds after 3 and 6 months, respectively. After the third vaccine dose, a significant increase in antibody titer was observed in all groups, with increases by a factor of ×51.6 in IN-Ds, ×30.1 in the controls and ×8.4 in PI-Ds. The median antibody titer after the third dose differed significantly between groups, and was the highest in PI-Ds: PI-Ds, 9090 (3300-15,000) BAU/mL; the controls, 6945 (2130-11,800); IN-Ds, 3715 (1470-7325) (p < 0.001). In conclusion, we observed similar degrees of antibody waning in all patients. After 3 months, over half of the infection-naïve dialysis patients had a very low antibody titer, and almost twenty percent of them had no antibodies at all. The humoral response to the third dose was very good, raising their titer of antibodies to a higher level than those in the general population who have received the primary two-dose scheme. The results support the administration of a complementary third dose of the mRNA vaccine for dialysis patients as soon as possible.

Predictors of Humoral Response to mRNA COVID19 Vaccines in Kidney Transplant Recipients: A Longitudinal Study-The COViNEPH Project.

BACKGROUND: The efficacy of SARS-CoV-2 vaccination among kidney transplant recipients (KTR) is low. The main goal of this study was to analyze factors that may influence the humoral response to vaccination. METHODS: We analyzed the titer magnitude of IgG antibodies directed against spike (S)-SARS-CoV-2 antigen after the second dose of the mRNA vaccine in 142 infection naïve KTR (83 men, i.e., 58.4%) with a median age (IQR) of 54 (41-63), and 36 respective controls without chronic kidney disease. mRNA-1273 or BNT162b2 were applied in 26% and 74% of KTR, respectively. RESULTS: S-specific immune response (seroconversion) was seen in 73 (51.41%) of KTR, and in all controls 36 (100%). Independent predictors of no response were elder age, shorter transplantation vintage, and a more than two-drug immunosuppressive protocol. In subgroup analyses, the seroconversion rate was highest among KTR without MMF/MPS treatment (70%), treated with no more than two immunosuppressants (69.2%), treated without corticosteroid (66.7%), younger patients aged <54 years (63.2%), and those vaccinated with the mRNA-1273 vaccine (62.16%). The independent predictors of higher S-antibody titer among responders were younger age, treatment with no more than two immunosuppressants, and the mRNA-1273 vaccination. CONCLUSIONS: Our study confirmed a low rate of seroconversion after vaccination with the mRNA vaccine in KTR. The major modifiable determinants of humoral response were the composition of the immunosuppressive protocol, as well as the type of vaccine. The latter could be taken into consideration when initial vaccination as well as booster vaccination is considered in KTR.

Safety and Tolerability of the BNT162b2 mRNA COVID-19 Vaccine in Dialyzed Patients. COViNEPH Project.

Background and Objectives: The Pfizer-BioNTech (BNT162b2) COVID-19 mRNA vaccine has demonstrated excellent efficacy and safety in phase 3 trials. However, no dialyzed patients were included, and therefore safety data for this patient group is lacking. The aim of the study was to assess the safety and tolerances of vaccinations with BNT162b2 performed in chronically dialyzed patients. Materials and Methods: We performed a prospective cohort study including a group of 190 dialyzed patients (65% male) at median age 68.0 (55-74) years. 169 (89.0%) patients were treated with hemodialysis and 21 (11.0%) with peritoneal dialysis. The control group consisted of 160 people (61% male) without chronic kidney disease at median age 63 (range 53-77) years. Both groups were vaccinated with BNT162b2 with a 21-day interval between the first and the second dose. Solicited local and systemic reactogenicity, unsolicited adverse events and antipyretic and pain medication use were assessed with a standardized questionnaire. The toxicity grading scales were derived from the FDA Center for Biologics Evaluation and Research guidelines. Results: 59.8% (dose 1), 61.4% (dose 2) and 15.9% (dose 1), 29.4% (dose 2) dialyzed patients reported at least one local and one systemic reaction respectively within seven days after the vaccination. Many local and systemic solicited reactions were observed less frequently in dialyzed patients than in the age and sex matched control group and much less frequently than reported in the pivotal study. They were mostly mild to moderate, short-lived, and more frequently reported in younger individuals and women. No related unsolicited adverse events were observed. Conclusions: We have shown here that BNT162b2, an mRNA vaccine from Pfizer-BioNTech against SARS-COV-2 is safe and well-tolerated by dialyzed patients. The results can be useful for the nephrological community to resolve patients' doubts and reduce their vaccine hesitancy.