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

Abstract

The immunogenicity of SARS‐CoV‐2 vaccines in kidney transplant recipients is limited, resulting in inadequately low serological response rates and low immunoglobulin (Ig) levels, correlating with reduced protection against death and hospitalization from COVID‐19. We retrospectively examined the time course of anti‐SARS‐CoV‐2 Ig antibody levels after up to five repeated vaccinations in 644 previously nonresponding kidney transplant recipients. Using anti SARS‐CoV‐2 IgG/IgA ELISA and the total Ig ECLIA assays, we compared antibody levels at 1 month with levels at 2 and 4 months, respectively. Additionally, we correlated the measurements of the used assays. Between 1 and 2 months, and between 1 and 4 months, mean anti‐SARS‐CoV‐2 Ig levels in responders decreased by 14% and 25%, respectively, depending on the assay. Absolute Ig values and time course of antibody levels showed high interindividual variability. Ig levels decreased by at least 20% in 77 of 148 paired samples with loss of sufficient serological protection over time occurring in 18 out of 148 (12.2%). IgG ELISA and total Ig ECLIA assays showed a strong positive correlation (Kendall’s tau = 0.78), yet the two assays determined divergent results in 99 of 751 (13.2%) measurements. IgG and IgA assays showed overall strong correlation but divergent results in 270 of 1.173 (23.0%) cases and only weak correlation of antibody levels in positive samples. Large interindividual variability and significant loss of serological response after 4 months supports repeated serological sampling and consideration of shorter vaccination intervals in kidney transplant recipients.