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The Role of mTOR Inhibitors in COVID-19 Outcomes Among Heart Transplant Recipients

Year: 2025

Type: article

Abstract: BACKGROUND: Heart failure (HF) remains a major global health challenge, with orthotopic heart transplantation (OHT) serving as the gold-standard therapy for end-stage disease. Chronic immunosuppression required to prevent graft rejection increases the risk of infections and malignancies. The COVID-19 pandemic underscored the particular vulnerability of transplant recipients to severe SARS-CoV-2 infection. Specific immunosuppressive agents used in OHT patients may differentially affect SARS-CoV-2 infection. In particular, mTOR inhibitors may modulate viral replication and immune responses, potentially influencing disease severity. OBJECTIVES: This study evaluated the impact of immunosuppressive regimens-particularly mTOR inhibitors-on COVID-19 outcomes in heart transplant recipients, comparing mTOR-based therapy (with or without calcineurin inhibitors, CNIs) to non-mTOR-based regimens. METHODS: This single-center retrospective observational study included 556 orthotopic heart transplant recipients (76.3% male; median age, 58 years) followed from March 2020 to March 2024. To compare patients receiving mTOR inhibitors with similar non-mTOR recipients, 3:1 propensity score matching was performed based on age, sex, and body mass index. Among the study population, 88 patients (15.8%) received mTOR inhibitors (everolimus or sirolimus), of whom 66 were concomitantly treated with calcineurin inhibitors and 22 without. Data were obtained from the National Health Fund database and clinical follow-ups. RESULTS: = 0.02), especially in the mTOR+CNI subgroup. Notably, no COVID-19-related deaths occurred in the mTOR CNI-free group. CONCLUSIONS: mTOR-based immunosuppression was non-inferior to standard therapy for COVID-19 outcomes. The absence of COVID-19-related deaths in patients on mTOR CNI-free regimens suggests potential protective effects that merit further investigation.

Source: Viruses

DOI: 10.3390/v18010029