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.