Benefits of Switching Mycophenolic Acid to Sirolimus on Serological Response after a SARS-CoV-2 Booster Dose among Kidney Transplant Recipients: A Pilot Study

Abstract

Kidney transplant recipients (KTRs) have a suboptimal immune response to COVID-19 vaccination due to the effects of immunosuppression, mostly mycophenolic acid (MPA). This study investigated the benefits of switching from the standard immunosuppressive regimen (tacrolimus (TAC), MPA, and prednisolone) to a regimen of mammalian target of rapamycin inhibitor (mTORi), TAC and prednisolone two weeks pre- and two weeks post-BNT162b2 booster vaccination. A single-center, opened-label pilot study was conducted in KTRs, who received two doses of ChAdOx-1 and a single dose of BNT162b2. The participants were randomly assigned to continue the standard regimen (control group, n = 14) or switched to a sirolimus (an mTORi), TAC, and prednisolone (switching group, n = 14) regimen two weeks before and two weeks after receiving a booster dose of BNT162b2. The anti-SARS-CoV-2 S antibody level after vaccination in the switching group was significantly greater than the control group (4051.0 [IQR 3142.0–6466.0] BAU/mL vs. 2081.0 [IQR 1077.0–3960.0] BAU/mL, respectively; p = 0.01). One participant who was initially seronegative in the control group remained seronegative after the booster dose. These findings suggest humoral immune response benefits of switching the standard immunosuppressive regimen to the regimen of mTORi, TAC, and prednisolone in KTRs during vaccination.

Effects of Sirolimus Treatment on Fetal Hemoglobin Production and Response to SARS-CoV-2 Vaccination: A Case Report Study

“…For instance, Cheng et al reported that the neutralizing antibody responses to a SARS-CoV-2 vaccine were unchanged in sirolimus-treated lymphangioleiomyomatosis patients, suggesting that monotherapy with sirolimus or other mTOR inhibitors does not prevent antibody responses to SARS-CoV-2 vaccines [40]. In other studies, a positive, beneficial effect of sirolimus and mTOR inhibitors on anti-SARS-CoV-2 antibody production was reported [24,41,42]. For instance, an immunosuppressive regimen based on low doses of the mTOR inhibitor everolimus was found by de Boer et al to be associated with a higher humoral response rate after COVID-19 vaccination in elderly kidney transplant recipients [42].…”