Observational study to assess the SARS-CoV-2 specific immune response in kidney transplant recipients (COVID-19 related immune response)

Due to the high risk of kidney transplant patients for severe COVID-19 pneumonia, we systematically investigated the vaccination response of our kidney transplant patients starting in spring 2021. Early on, we showed that kidney transplanted patients have a significantly reduced vaccination response compared to normal healthy individuals. After second vaccination, only 32/135 (24%) kidney transplanted patients showed SARS-CoV-2 specific antibodies compared to a 100% vaccination response of the 134 healthy controls studied. In those transplant patients who showed seroconversion in the commercial assays, we also examined the formation of neutralizing antibodies to the B.1.1.7 (alpha), B.1.351 (beta), and B.1.617.2 (delta) variants with a live virus assay. Here we showed that kidney transplanted patients neutralized the three variants of concern significantly worse than healthy controls (Benning et al., CJASN 2022). In another study, we compared SARS-CoV-2 specific immunity of kidney transplanted patients after infection with vaccine-induced immunity. We showed that COVID-19 recovered kidney transplanted patients exhibited good cross-reactivity against SARS-CoV-2 wild type as well as B.1.1.7 (alpha), B.1.351 (beta), and B.1.617.2 (delta) variants, independent of the disease-inducing SARS-CoV-2 type. In addition, COVID-19 recovered kidney transplant patients neutralized the tested variants better than COVID-19 vaccinated patients, although commercial assays showed similarly high antibody titers in both groups (Benning et al., Kidney International, 2022). A third vaccination was subsequently recommended for immunocompromised patients in the fall of 2021 because of the markedly limited vaccine response and high risk. In another work, we showed that kidney transplant patients compared to healthy controls were significantly less likely to develop SARS-CoV-2 specific antibodies even after third vaccination. Only 29/49 (59%) of kidney transplanted patients were able to neutralize SARS-CoV-2 wild type and B.1.617.2 (delta) variant after third time vaccination. In addition, this time we also tested against the now newly emerging B.1.1.529 (omicron) variant of concern and showed that both healthy controls and kidney transplanted patients neutralized the omicron variant significantly worse than the SARS-CoV-2 wild type or the B.1.617.2 (delta) variant (Benning et al., American Journal of Transplantation, 2022). Because of the high mortality during the delta wave, the emerging highly infectious omicron wave, and the inadequate vaccine response in our kidney transplant patients, we decided to reduce immunosuppressive therapy for a fourth vaccination in patients with no preexisting risk of rejection to increase immunogenicity. Indeed, we demonstrated that short-term reduction of immunosuppression (pausing mycophenolic acid) improved vaccine response and was not associated with an increased risk of rejection in the short-term (Benning et al, Frontiers in Medicine, 2022; Kühn et al, Transplantation, 2023).