Intensity of mycophenolate mofetil treatment is associated with an impaired immune response to SARS-CoV-2 vaccination in kidney transplant recipients

Kantauskaite, Marta; Müller, Lisa; Kolb, Thilo; Fischer, Svenja; Hillebrandt, Jonas; Ivens, Katrin; Andree, Marcel; Luedde, Tom; Orth, Hans Martin; Adams, Ortwin; Schaal, Heiner; Schmidt, Claudia; Königshausen, Eva; Rump, Lars C; Timm, Jörg; Stegbauer, Johannes

Kidney transplant recipients (KTRs) are extremely vulnerable to SARS-CoV-2 infection and show an impaired immune response to SARS-CoV-2 vaccination. We analyzed factors related to vaccination efficiency in KTRs. In a multicenter prospective observational study (NCT04743947), IgG antibodies levels against SARS-CoV-2 spike S1 subunit and their neutralization capacity after SARS-CoV-2 vaccination were analyzed in 225 KTRs and compared to 176 controls. After the vaccination, 56 (24.9%) KTRs became seropositive of whom 68% had neutralizing antibodies. This immune response was significantly lower compared to controls [239 (78-519) BAU/ml versus 1826 (560-3180) BAU/ml for KTRs and controls, p<0.0001]. The strongest predictor for an impaired response was mycophenolate mofetil (MMF) treatment. Multivariate regression analysis revealed that MMF-free regimen was highly associated with seroconversion (OR 13.25, 95% CI 3.22-54.6; p<0.001). In contrast, other immunosuppressive drugs had no significant influence. 187 out of 225 KTRs were treated with MMF of whom 26 (13.9%) developed antibodies. 23 of these seropositive KTRs had a daily MMF dose ≤1g. Furthermore, higher trough MMF concentrations correlated with lower antibody titers (R -0.354, p<0.001) supporting a dose-dependent unfavorable effect of MMF. Our data indicate that MMF dose modification could lead to an improved immune response.