{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T11:29:46Z","timestamp":1766575786951,"version":"3.48.0"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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\u2014particularly mTOR inhibitors\u2014on 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: Overall mortality was 13.5%, and COVID-19-related mortality 3.2%. COVID-19 incidence was 33% in the mTOR group versus 36.7% in the non-mTOR group (p = 0.52). Hospitalization rates were 3.4% and 6.4% (p = 0.29), respectively. All-cause mortality was higher among mTOR users (21.6% vs. 11.7%, p = 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.<\/jats:p>","DOI":"10.3390\/v18010029","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T11:22:14Z","timestamp":1766575334000},"page":"29","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of mTOR Inhibitors in COVID-19 Outcomes Among Heart Transplant Recipients"],"prefix":"10.3390","volume":"18","author":[{"given":"Agnieszka","family":"Kuczaj","sequence":"first","affiliation":[{"name":"Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Silesian Center for Heart Diseases, M.C. Sk\u0142odowskiej 9, 41-800 Zabrze, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9930-5864","authenticated-orcid":false,"given":"Szymon","family":"Warwas","sequence":"additional","affiliation":[{"name":"Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Silesian Center for Heart Diseases, M.C. Sk\u0142odowskiej 9, 41-800 Zabrze, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miko\u0142aj","family":"Tyrka","sequence":"additional","affiliation":[{"name":"Students\u2019 Scientific Association, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, M.C. Sk\u0142odowskiej 9, 41-800 Zabrze, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u0142a\u017cej","family":"Skotnicki","sequence":"additional","affiliation":[{"name":"Students\u2019 Scientific Association, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, M.C. Sk\u0142odowskiej 9, 41-800 Zabrze, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Szymecki","sequence":"additional","affiliation":[{"name":"Students\u2019 Scientific Association, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, M.C. Sk\u0142odowskiej 9, 41-800 Zabrze, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4340-5902","authenticated-orcid":false,"given":"Oliwia","family":"Jewu\u0142a","sequence":"additional","affiliation":[{"name":"Students\u2019 Scientific Association, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, M.C. Sk\u0142odowskiej 9, 41-800 Zabrze, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Szymon","family":"Pawlak","sequence":"additional","affiliation":[{"name":"Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Silesian Center for Heart Diseases, M.C. Sk\u0142odowskiej 9, 41-800 Zabrze, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Przyby\u0142owski","sequence":"additional","affiliation":[{"name":"Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Silesian Center for Heart Diseases, M.C. Sk\u0142odowskiej 9, 41-800 Zabrze, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8945-7351","authenticated-orcid":false,"given":"Tomasz","family":"Hrapkowicz","sequence":"additional","affiliation":[{"name":"Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Silesian Center for Heart Diseases, M.C. Sk\u0142odowskiej 9, 41-800 Zabrze, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"ref_1","unstructured":"Rzhanyi, M., Pechenenko, A., Alcocer, J., Sandoval Mart\u00ednez, E., and Quintana, E. (2023). Cardiac retransplantation. Multimed. Man. Cardiothorac. Surg. MMCTS."},{"key":"ref_2","first-page":"mmv035","article-title":"Orthotopic heart transplantation: The bicaval technique","volume":"2015","author":"Toscano","year":"2015","journal-title":"Multimed. Man. Cardiothorac. Surg. MMCTS"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.bpa.2017.06.003","article-title":"Long-term outcomes and management of the heart transplant recipient","volume":"312","author":"McCartney","year":"2017","journal-title":"Best Pract. Res. Clin. 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