Frontiers in Immunology (Jan 2023)

Ferric carboxymaltose and SARS-CoV-2 vaccination-induced immunogenicity in kidney transplant recipients with iron deficiency: The COVAC-EFFECT randomized controlled trial

  • Joanna Sophia J. Vinke,
  • Dania H. A. Altulea,
  • Michele F. Eisenga,
  • Renate L. Jagersma,
  • Tessa M. Niekolaas,
  • Debbie van Baarle,
  • Marieke van Der Heiden,
  • Maurice Steenhuis,
  • Theo Rispens,
  • Wayel H. Abdulahad,
  • Jan-Stephan F. Sanders,
  • Martin H. De Borst

DOI
https://doi.org/10.3389/fimmu.2022.1017178
Journal volume & issue
Vol. 13

Abstract

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BackgroundKidney transplant recipients (KTRs) have an impaired immune response after vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Iron deficiency (ID) may adversely affect immunity and vaccine efficacy. We aimed to investigate whether ferric carboxymaltose (FCM) treatment improves humoral and cellular responses after SARS-CoV-2 vaccination in iron-deficient KTRs.MethodsWe randomly assigned 48 iron-deficient KTRs to intravenous FCM (1-4 doses of 500mg with six-week intervals) or placebo. Co-primary endpoints were SARS-CoV-2-specific anti-Receptor Binding Domain (RBD) Immunoglobulin G (IgG) titers and T-lymphocyte reactivity against SARS-CoV-2 at four weeks after the second vaccination with mRNA-1273 or mRNA-BNT162b2.ResultsAt four weeks after the second vaccination, patients receiving FCM had higher plasma ferritin and transferrin saturation (P<0.001 vs. placebo) and iron (P=0.02). However, SARS-CoV-2-specific anti-RBD IgG titers (FCM: 66.51 [12.02-517.59] BAU/mL; placebo: 115.97 [68.86-974.67] BAU/mL, P=0.07) and SARS-CoV-2-specific T-lymphocyte activation (FCM: 93.3 [0.85-342.5] IFN-ɣ spots per 106 peripheral blood mononuclear cells (PBMCs), placebo: 138.3 [0.0-391.7] IFN-ɣ spots per 106 PBMCs, P=0.83) were not significantly different among both arms. After the third vaccination, SARS-CoV-2-specific anti-RBD IgG titers remained similar between treatment groups (P=0.99).ConclusionsIntravenous iron supplementation efficiently restored iron status but did not improve the humoral or cellular immune response against SARS-CoV-2 after three vaccinations.

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