Enhanced Humoral Immune Response After COVID-19 Vaccination in Elderly Kidney Transplant Recipients on Everolimus Versus Mycophenolate Mofetil-containing Immunosuppressive Regimens

Abstract

Background: Elderly kidney transplant recipients (KTRs) represent almost one third of the total kidney transplant population. These patients have a very high coronavirus disease 2019 (COVID-19)-related mortality, whereas their response to COVID-19 vaccination is impaired. Finding ways to improve the COVID-19 vaccination response in this vulnerable population is of uttermost importance.

Methods: In the OPTIMIZE trial, we randomly assign elderly KTRs to an immunosuppressive regimen with standard-exposure calcineurin inhibitor (CNI), mycophenolate mofetil, and prednisolone or an adapted regimen with low dose CNI, everolimus, and prednisolone. In this substudy, we measured the humoral response after 2 (N = 32) and 3 (N = 22) COVID-19 mRNA vaccinations and the cellular response (N = 15) after 2 vaccinations.

Results: . The seroconversion rates of elderly KTRs on a standard immunosuppressive regimen were only 13% and 38% after 2 and 3 vaccinations, respectively, whereas the response rates of KTRs on the everolimus regimen were significantly higher at 56% ( P = 0.009) and 100% ( P = 0.006). Levels of severe acute respiratory syndrome coronaVirus 2 IgG antibodies were significantly higher at both time points in the everolimus group ( P = 0.004 and P < 0.001). There were no differences in cellular response after vaccination.

Conclusions: An immunosuppressive regimen without mycophenolate mofetil, a lower CNI dose, and usage of everolimus is associated with a higher humoral response rate after COVID-19 vaccination in elderly KTRs after transplantation. This encouraging finding should be investigated in larger cohorts, including transplant recipients of all ages.

FIGURE 1.

Patient flow diagram. COVID-19, coronavirus disease 2019; KTR, kidney transplant recipient; RTX, rituximab; UMCG, University Medical Center Groningen.

FIGURE 2.

IgG (spike receptor-binding domain [S-RBD]) antibody level after 2 vaccinations. The dotted line indicates threshold for seroresponse. Maximal threshold of quantification is 40 000 AU/mL. AU, arbitrary units; EVR, everolimus; MMF, mycophenolate mofetil.

FIGURE 3.

Changes in IgG (spike receptor-binding domain [S-RBD]) antibody level between second and third vaccination. The dotted line indicates threshold for seroresponse. Maximal threshold of quantification is 40 000 AU/mL. AU, arbitrary units; EVR, everolimus; MMF, mycophenolate mofetil.