mTOR inhibitors, mycophenolates, and other immunosuppression regimens on antibody response to SARS-CoV-2 mRNA vaccines in solid organ transplant recipients

A recent study concluded that SARS-CoV-2 mRNA vaccine responses were improved among transplant patients taking mTOR inhibitors (mTORi). This could have profound implications for vaccine strategies in transplant patients; however, limitations in the study design raise concerns about the conclusions. To address this issue more robustly, in a large cohort with appropriate adjustment for confounders, we conducted various regression- and machine learning-based analyses to compare antibody responses by immunosuppressive agents in a national cohort ( n = 1037). MMF was associated with significantly lower odds of positive antibody response (aOR = 0.09 0.13 0.18 ). Consistent with the recent mTORi study, the odds tended to be higher with mTORi (aOR = 1.00 1.45 2.13 ); however, importantly, this seemingly protective tendency disappeared (aOR = 0.47 0.73 1.12 ) after adjusting for MMF. We repeated this comparison by combinations of immunosuppression agents. Compared to MMF + tacrolimus, MMF-free regimens were associated with higher odds of positive antibody response (aOR = 2.39 4.26 7.92 for mTORi+tacrolimus; 2.34 5.54 15.32 for mTORi-only; and 6.78 10.25 15.93 for tacrolimus-only), whereas MMF-including regimens were not, regardless of mTORi use (aOR = 0.81 1.54 2.98 for MMF + mTORi; and 0.81 1.51 2.87 for MMF-only). We repeated these analyses in an independent cohort ( n = 512) and found similar results. Our study demonstrates that the recently reported findings were confounded by MMF, and that mTORi is not independently associated with improved vaccine responses.