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

Abstract

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 Numberwww.ClinicalTrials.gov, identifier: NCT04 905 862

Molnupiravir When Used Alone Seems to Be Safe and Effective as Outpatient COVID-19 Therapy for Hemodialyzed Patients and Kidney Transplant Recipients

“…Terminal kidney failure, immunosuppressive therapy, and concomitant diseases make the population of HD/KTRs especially vulnerable to severe COVID-19. HD patients develop an impaired cellular and humoral response to COVID-19 vaccination compared to the general population [ 5 ]. KTRs show a preserved symptom-dependent humoral response to SARS-CoV-2 infection [ 17 ].…”

“…Also, the response to vaccination in HD patients and KTRs is much lower than in the general population [ 5 ]. For the aforementioned reasons, using effective drugs against COVID-19 in these patient groups is essential.…”

Outcomes of vaccinations against respiratory diseases in patients with end-stage renal disease undergoing hemodialysis: A systematic review and meta-analysis

“…These studies used various vaccine platforms (including mRNA, inactivated, viral vector and heterologous vaccines) as well as different units of measurements. Table 2 summarizes the comparison of IgG levels between HD and control groups following COVID-19 vaccination obtained from the 30 studies [ 16 – 20 , 22 – 25 , 27 – 29 , 31 , 33 – 36 , 38 – 40 , 43 , 44 , 46 – 48 , 51 , 53 , 54 , 59 ]. Overall, twenty-nine studies demonstrated lower IgG levels after COVID-19 vaccination in HD patients compared to healthy controls, whereas only one study by Panizo showed a contrary finding [ 36 ].…”

Impact of COVID‐19 on maintenance peritoneal dialysis patients and providers: A review

“…One study reported that 35% of the studied dialysis patients (130 HD patients and 13 PD patients) had low or undetectable levels of IgG antibodies against SARS-CoV-2 Spike (S) protein following two doses of the BNT162b2 or mRNA-1273 vaccines [63]. Despite this overall reduced response to vaccination, it should be noted that individual studies as well as a meta-analysis have demonstrated stronger humoral responses to vaccination in PD patients compared to HD patients [64,65]. For example, Tylicki et al's study showed that PD patients (n = 21) had more robust anti-S IgG antibody titers following both the first (p = 0.034) and second (p = 0.008) doses of the BNT162b2 vaccine compared to HD patients (n = 35) [66].…”