In particular, mTOR inhibitors may modulate viral replication and immune responses, potentially influencing disease severity.<h4>Objectives</h4>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.<h4>Methods</h4>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. The gene discussed is MTOR; the disease is COVID-19.