COVID-19 Vaccination Response in Tacrolimus Treated Kidney Transplant Recipients with and without Mycophenolate Mofetil: Follow-Up of a Randomized Controlled Trial

ABSTRACT

Purpose: To investigate the effect of mycophenolate mofetil (MMF) on SARSCoV- 2 vaccination response in kidney transplant recipients using the standard immunosuppressive regimen of tacrolimus (TAC) and MMF. Method(s) A randomized controlled trial in immunologically low risk kidney transplant recipients was performed (EudraCT nr. 2014-001372-66). Patients were randomized to standard TAC/MMF or TAC monotherapy (TACmono) from 9 months onwards, without steroids. Antibody based immune responses to SARS-CoV-2 vaccination (mRNA-1273 or BNT162b2) were investigated in a central laboratory, as part of the RECOVAC Antibody study (EudraCT nr. 2021-283 001520-18), 4-8 weeks after the second vaccination. Measurement involved the presence of antibodies against the receptor binding domain (RBD) of the SARS-CoV-2 S-protein (IgG anti-RBD antibody) using the Sanquin anti-SARS-CoV-2 RBD IgG ELISA assay. Patients were classified as non-responders (<=50 BAU/mL), low-responders (50-300 BAU/ mL) and responders (>300 BAU/mL). Result(s) Between 2015 and 2018, 79 recipients were randomized to TAC/MMF (n=41) and TACmono (n=38). At the outbreak of the COVID-19 pandemic in early 2020, 67 patients were alive with a functioning graft (TAC/MMF n=35, TACmono n=32). In 27 patients antibody responses could be established Ten patients were excluded from the analyses due to symptomatic COVID-19 infection and 1 due to a positive nucleocapsid test, possibly from an asymptomatic infection. The rest did not participate in the vaccination study, because of ChAdOx1-S, age >80 years or lack of informed consent. Mean age was 64 (43-75) years, median time after transplantation 4.2 (3.0-6.5) years and eGFR was 53 (36-105) ml/min/1.73m2. TAC trough levels were 6.6 (+/-0.3) mug/L in both groups, and MMF dose was 1000 mg daily (range 500- 2000) in TAC/MMF. Median SARS-CoV-2 Spike S1-specific IgG antibody levels were 37.3 BAU/ml in TAC/MMF (5 non, 7 low, 1 responder) and 715.6 BAU/ml in TACmono (1 non, 6 low, 7 responders, p =0.004, figure 1). Of note is that antibody levels of >1000 BAU/ml, as a presumed threshold for protection against Omicron (B.1.1.529), was reached in 1/13 TAC/MMF and 7/14 TACmono patients (p=0.03). Conclusion(s) In this controlled study mycophenolate mofetil on top of tacrolimus severely hampered serological COVID-19 vaccination response.