Discussion
The main finding of this study is that correction of ID with FCM does not improve the humoral or cellular post-vaccination immune response against SARS-CoV-2 in KTRs. Although iron-deficient KTRs who were treated with FCM showed a significant increase in plasma ferritin and TSAT compared to placebo, there was no difference in SARS-CoV-2-specific anti-RBD IgG concentration, seroconversion rate or number of IFN-ɣ-producing T-lymphocytes after vaccination. These results are in contrast with studies in other populations, reporting improved vaccination efficacy after iron supplementation (Notably, although there were no significant differences in antibody response between the treatment groups after any of the three vaccination doses, a small advance of the placebo-treated group seemed to decrease after each vaccination dose, until after the third dose, the median SARS-CoV-2-specific anti-RBD IgG concentration was slightly higher in the FCM-treated group. Another study (In the current study, only 68% of patients had a positive SARS-CoV-2-specific anti-RBD IgG response and 61% had SARS-CoV-2-specific T-lymphocyte activation after the second vaccination. These numbers are similar to results of other studies among KTRs (Our study has several strengths as well as limitations. We had the unique chance to assess vaccine efficacy within the scope of a running clinical trial assessing the impact of treatment with FCM versus placebo in iron-deficient KTRs. Another strength is the simultaneous availability of SARS-CoV-2-specific anti-RBD IgG concentration and data on SARS-CoV-2-specific T-lymphocyte activation. Limitations include the relatively small number of participants; nevertheless, since we did not find any trend towards a positive effect, a larger sample size would be unlikely to lead to a different outcome. The current study involved patients participating in an ongoing clinical trial who had not received all study treatments at the time of the Dutch national COVID-19 vaccination campaign, as well as patients who had finished their participation in the trial up to a year before vaccination. Therefore, there was considerable heterogenicity in the number of treatments received at the time of vaccination and the time between the last treatment and vaccination. Nevertheless, there was a clear difference in iron status between the two arms at the time of measurements four weeks after the second vaccination. At the time of the first vaccination, only a small amount of serum was collected from a finger capillary blood sample (collected with a fingerpick sampled at home). Unfortunately, these samples did not allow us to measure iron status parameters at that time. Furthermore, most patients received the mRNA-1273 vaccine whereas some received the mRNA-BNT162b2 vaccine. However, the results were robust in a sensitivity analysis excluding patients who were vaccinated with mRNA-BNT162b2 (In conclusion, in KTRs with ID, intravenous iron supplementation efficiently restored iron status but did not improve the humoral or cellular immune response against SARS-CoV-2 after three vaccinations.