Neutralization of the SARS-CoV-2 Delta and Omicron Variants in Previous Non-Responder Kidney Transplant Recipients After Short-Term Withdrawal of Mycophenolic Acid

ABSTRACT

Background: Response to COVID-19 vaccination is significantly impaired in kidney transplant recipients (KTR) even after three doses of an mRNA vaccine. Adaptive immunization strategies are urgently needed to ultimately protect these patients from COVID-19. Method(s) We determined the effect of an additional mRNA-1273 vaccine dose in 76 non-responder KTR with at least 3 previous vaccine doses. In 43 KTR with triple immunosuppressive therapy including a calcineurin inhibitor (CNI), mycophenolic acid (MPA), and corticosteroids (CS), MPA was withdrawn to investigate the effect of short-term MPA withdrawal on COVID-19 vaccine immunogenicity. Seroconversion was determined four weeks after vaccination. In addition, neutralization of the delta and omicron variants was determined using a live-virus assay. In patients with temporary MPA withdrawal, donor-specific antibodies (DSA) and donor-derived cell-free DNA (dd-cfDNA) were monitored before MPA withdrawal and at follow-up. Result(s) After vaccination, 24/69 (35%) KTR showed anti-spike S1 IgG antibodies above the predefined cut-off, excluding 7 breakthrough infections that occurred during follow-up. SARS-CoV-2 specific antibodies were significantly higher in patients where MPA was withdrawn (Figure 1A). Neutralization of the delta variant was significantly better compared to neutralization of the omicron variant (Figure 1B). Higher SARSCoV-2-specific antibodies were associated with better in-vitro neutralization of the delta and omicron variants (Figure 1C). In KTR with MPA withdrawal, no significant changes in S-creatinine, proteinuria or dd-cfDNA were observed. No acute rejection episode occurred during short-term follow-up. However, resurgence of pre-existing DSA was observed in 7 patients and the development of de novo DSA in one patient. Conclusion(s) MPA withdrawal seems reasonable to increase immunogenicity of SARS-CoV-2 vaccination. For safety reasons, this may only be offered to patients without current or previous DSA.