mTOR Inhibitor Use Is Associated With a Favorable Outcome of COVID-19 in Patients of Kidney Transplant: Results of a Retrospective Study

Abstract

IntroductionIn solid organ transplant recipients, COVID-19 is associated with a poor prognosis because of immunosuppression. Some studies suggest a potential therapeutic role of mammalian Target of Rapamycin (mTOR) inhibitors in SARS-CoV-2 infection. This study aimed to assess the impact of mTOR employment on the evolution and outcome of SARS-CoV-2 infection in solid organ transplant recipients.MethodsWe enrolled kidney transplant patients attending the Azienda Ospedaliera Universitaria Federico II in Naples and followed up on these patients from March 2020 to June 2021. We evaluated the risk of acquiring the SARS-CoV-2 infection, the clinical presentation of the disease, and its outcome together with the type of immunosuppressive therapy. Finally, we assessed the impact of mTOR inhibitors on relevant clinical metrics of SARS-CoV-2 infection.ResultsWe enrolled 371 patients, of whom 56 (15.1%) contracted SARS-CoV-2 infection during the period of the study. There were no differences observed among the different immunosuppressive therapies concerning the risk of acquiring SARS-CoV-2 infection. In contrast, the type of immunosuppressive therapy had a significant impact on the outcome of the disease. In detail, patients who received mTOR inhibitors, as part of their immunosuppressive therapy, compared to other regimens had a lower chance of developing a moderate or severe form of the disease (OR = 0.8, 95, CI: (0.21–0.92), P = 0.041).ConclusionIn kidney transplant patients, the use of mTOR inhibitors as part of an immunosuppressive regimen is associated with a better prognosis in the case of COVID-19.

Role of mTOR inhibitor in the cellular and humoral immune response to a booster dose of SARS-CoV-2 mRNA-1273 vaccine in kidney transplant recipients

“…Nevertheless, this beneficial effect of mTORi after two doses of vaccine was no maintained in the adjusted model in our cohort, findings also noted by Bae (33). Several authors found similar results with MPA and mTORi in different groups of patients who received two doses (33)(34)(35)(36)(37), even proposing the temporary suspension of treatment during the vaccination process (38). But we go further and performed an analysis of immune response after the third or booster dose and different results were observed.…”

COVID-19 in solid organ transplant recipients after 2 years of pandemic: Outcome and impact of antiviral treatments in a single-center study

“…The finding of the favorable impact of mTOR inhibitors confirmed what was reported by Heldman et al ( 22 ) and what reported from our previous experience, in which the patients who received mTOR inhibitors, as part of their immunosuppressive therapy, compared to other regimens had a lower chance of developing a moderate or severe form of the disease [OR = 0.8, 95, CI: (0.21–0.92), p = 0.041] ( 36 ). However, our own data are not in agreement to what has been reported by Genuardi et al ( 37 ).…”

Protracted COVID‐19 pneumonitis early post‐ABO incompatible kidney transplantation: Management considerations and the role of whole genome sequencing

“…12 The optimal management of transplant immunosuppression during COVID-19 is unclear. We stopped MMF and later introduced a mTOR inhibitor, as these have been associated with less and more favourable outcomes, respectively, in KT recipients with COVID-19, 13,14 despite the potential for everolimus to cause pulmonary toxicity. 15 F I G U R E 3 Whole genome sequencing analysis of seven samples collected between week 4 and 18 post initial infection.…”