Role of Immunosuppression on Efficacy of Anti-SARS-CoV-2 Vaccines in Heart Transplanted (HT) Patients

PURPOSE: Vaccines against COVID-19 have a lower efficacy in HT patients (pts); factors influencing their immunogenicity are unknown. The aim of this study is to investigate the role of immunosuppression on mRNA vaccines efficacy. METHODS: We included all HT pts followed in our Center completing the vaccine cycle (03-06/21), for whom levels of IgG anti-RBD after the second dose were known, excluding those with a previous COVID infection. Demography, immunosuppression (drugs and trough blood level), lymphocyte count, previous rejection episodes were collected before the first dose. The endpoint was vaccine-induced immunization after the second dose according to our laboratory's threshold of IgG anti-RBD. RESULTS: Among 201 vaccinated, IgG anti-RBD values were available for 63 pts at 2± 1 months after the second dose (22±3 days after the first; 89% BNT162b2; 60±11 yrs, 5±1 yrs from HT, 75% males, 3 with rejection > 1R in the previous 6 months). All pts were on CNI-inhibitors (35% tacrolimus, TAC, 65% cyclosporine, CyA), 57% on MMF, 23% mTOR, 69% steroids (CS). 41.7% had no response to vaccine. At univariate analysis the predictors of lack of response to vaccine were: MMF (43% vs 71%), TAC vs CSA (27% vs 73%), steroids (46% vs 76%), steroid dose > 5mg, lymphocytes <18% of leukocytes (both identified by ROC), more than 5 years from HT; mTOR was more likely associated with protection (80% vs 49%), p<0.05 all. Importantly, age was not predictive of immunogenicity. At stepwise multivariate analysis all these factors maintained statistical significance (p<0.05 all). IgG anti-RBD values were influenced by low lymphocytes, steroids and TAC trough levels (p< 0.05 all).Response to vaccine was the lowest for MMF+TAC+CS (23.1%), intermediate for MMF+CyA+CS (53.3%) and steroid-free regimens (68.7%), highest (87.5%) for mTOR+CNI+CS (20%,23%,24%,23% of pts, p=0.01). No rejection episodes were registered 3 months after the second dose of vaccine. CONCLUSION: While confirming a low response to COVID-19 vaccines a in HT pts, our study underscores the negative effect of immunosuppression, particularly of MMF, high doses of steroids and TAC. Given that MMF is a cornerstone of most protocols, from these results it arises the hypothesis (to be tested in larger studies) if switching stable patients from TAC to Cya or to lower steroid doses may favor the attempts to increase the response to vaccines.