Abstract
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 = 0.090.130.18). Consistent with the recent mTORi study, the odds tended to be higher with mTORi (aOR = 1.001.452.13); however, importantly, this seemingly protective tendency disappeared (aOR = 0.470.731.12) 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 = 2.394.267.92 for mTORi+tacrolimus; 2.345.5415.32 for mTORi-only; and 6.7810.2515.93 for tacrolimus-only), whereas MMF-including regimens were not, regardless of mTORi use (aOR = 0.811.542.98 for MMF + mTORi; and 0.811.512.87 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.
Original language | English (US) |
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Pages (from-to) | 3137-3142 |
Number of pages | 6 |
Journal | American Journal of Transplantation |
Volume | 22 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2022 |
Keywords
- clinical research/practice
- immunosuppressant
- immunosuppression/immune modulation
- infection and infectious agents
- infection and infectious agents—viral: SARS-CoV-2/COVID-19
- infectious disease
- Graft Rejection/prevention & control
- Humans
- Mycophenolic Acid/therapeutic use
- Kidney Transplantation
- Immunosuppression Therapy
- Transplant Recipients
- SARS-CoV-2
- Tacrolimus
- MTOR Inhibitors
- COVID-19 Vaccines
- Antibody Formation
- COVID-19/prevention & control
- Immunosuppressive Agents/therapeutic use
- TOR Serine-Threonine Kinases
ASJC Scopus subject areas
- Transplantation
- Pharmacology (medical)
- Immunology and Allergy