Serological Response to Three, Four and Five Doses of SARS-CoV-2 Vaccine in Kidney Transplant Recipients

Abstract

Mortality from COVID-19 among kidney transplant recipients (KTR) is high, and their response to three vaccinations against SARS-CoV-2 is strongly impaired. We retrospectively analyzed the serological response of up to five doses of the SARS-CoV-2 vaccine in KTR from 27 December 2020 until 31 December 2021. Particularly, the influence of the different dose adjustment regimens for mycophenolic acid (MPA) on serological response to fourth vaccination was analyzed. In total, 4277 vaccinations against SARS-CoV-2 in 1478 patients were analyzed. Serological response was 19.5% after 1203 basic immunizations, and increased to 29.4%, 55.6%, and 57.5% in response to 603 third, 250 fourth, and 40 fifth vaccinations, resulting in a cumulative response rate of 88.7%. In patients with calcineurin inhibitor and MPA maintenance immunosuppression, pausing MPA and adding 5 mg prednisolone equivalent before the fourth vaccination increased the serological response rate to 75% in comparison to the no dose adjustment (52%) or dose reduction (46%). Belatacept-treated patients had a response rate of 8.7% (4/46) after three vaccinations and 12.5% (3/25) after four vaccinations. Except for belatacept-treated patients, repeated SARS-CoV-2 vaccination of up to five times effectively induces serological response in kidney transplant recipients. It can be enhanced by pausing MPA at the time of vaccination.

Development and Validation of Multivariable Prediction Models of Serological Response to SARS-CoV-2 Vaccination in Kidney Transplant Recipients

“…Details of the underlying patient population, as well as the assays and cutoffs used have been previously reported. 5 Briefly, KTR received up to five doses of SARS-CoV-2 vaccine in case of sustained lack of sufficient serological response to vaccination at our institution, usually combined with reduction or pausing MPA for fourth and fifth vaccination. For the enzyme-linked immunosorbent assays (ELISA) for the detection of IgG antibodies against the S1 domain of the SARS-CoV-2 spike (S) protein in serum (Anti-SARS-CoV-2-ELISA (IgG), EUROIMMUN Medizinische Labordiagnostika AG, Lübeck, Germany), samples with a cutoff index ≥ 1.1 (in comparison to the previously obtained cut-off value of the calibrator) were considered to be positive, samples with a cutoff index ≥ 0.8, and < 1.1 were considered low positive, and samples with a cutoff index <0.8 were considered negative, as suggested by the manufacturer.…”

“…4 Existing data comprises risk factors identified through multivariable analyses, which are helpful to identify factors associated with insufficient vaccination response but are not easily interpretable for the single patient or vaccination. 5-7 Specifically, no tool exists to predict response to a vaccination in a particular patient. Risk calculators can build a bridge to help assess the likelihood of vaccination success in an individual and help decide between different possible actions to take such as passive or active immunization or adjustment of immunosuppressive medication.…”

Declining Course of Humoral Immune Response in Initially Responding Kidney Transplant Recipients after Repeated SARS-CoV-2 Vaccination

“…Reduced immunogenicity of SARS-CoV-2 vaccines leads to a low rate of sufficient serological response and lower levels of antibodies in KTR [ 8 , 9 , 10 ]. Specifically, only 19–54% of KTR showed sufficient response after two doses of the vaccine [ 8 , 11 , 12 ]. Similarly, only 42% of KTR exhibited vaccination response after a third dose of the vaccine, while seroconversion reached 95% in dialysis patients and 98% in medical personnel [ 10 , 12 , 13 ].…”

“…Specifically, only 19–54% of KTR showed sufficient response after two doses of the vaccine [ 8 , 11 , 12 ]. Similarly, only 42% of KTR exhibited vaccination response after a third dose of the vaccine, while seroconversion reached 95% in dialysis patients and 98% in medical personnel [ 10 , 12 , 13 ]. The result is a lack of protection against COVID-19 in KTR as compared with healthy individuals [ 14 , 15 ].…”

“…A third vaccination was recommended early on for KTR in order to increase immune response [ 16 ]. Further, repeated vaccinations under modulated immunosuppression effectively increase protection, yet a substantial number of patients do not reach protective antibody levels [ 12 , 17 , 18 ].…”