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Published on: June 26, 2020
The Role of mTOR Inhibitors in COVID-19 Outcomes Among Heart Transplant Recipients
Agnieszka Kuczaj1, Szymon Warwas1, Mikołaj Tyrka2
1Department 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. Skłodowskiej 9, 41-800 Zabrze, Poland.
Insights
Mammalian target of rapamycin (mTOR) inhibitors in heart transplant recipients did not worsen COVID-19 outcomes. However, mTOR inhibitors without calcineurin inhibitors (CNIs) showed no COVID-19 related deaths, suggesting a potential protective effect.
Area of Science:
- Immunology
- Transplantation Medicine
- Infectious Diseases
Background:
- Heart failure (HF) is a significant global health issue, with heart transplantation (OHT) as the primary treatment for end-stage disease.
- Immunosuppression post-OHT increases risks of infections and malignancies, notably severe SARS-CoV-2 infection during the COVID-19 pandemic.
- Specific immunosuppressants, like mTOR inhibitors, may influence viral replication and immune responses, impacting COVID-19 severity in OHT patients.
Purpose of the Study:
- To assess the impact of mTOR inhibitors on COVID-19 outcomes in OHT recipients.
- To compare COVID-19 outcomes between mTOR-based immunosuppressive regimens (with or without CNIs) and non-mTOR-based regimens.
Main Methods:
- A single-center retrospective observational study of 556 OHT recipients from March 2020 to March 2024.
- Propensity score matching (3:1) was used to compare mTOR inhibitor users (n=88) with non-mTOR recipients based on age, sex, and BMI.
- Data collected from the National Health Fund and clinical follow-ups.
Main Results:
- Overall mortality was 13.5%, with 3.2% COVID-19-related mortality.
- COVID-19 incidence (33% vs. 36.7%) and hospitalization rates (3.4% vs. 6.4%) were similar between mTOR and non-mTOR groups.
- All-cause mortality was higher in mTOR users (21.6% vs. 11.7%, p=0.02), particularly in the mTOR+CNI subgroup. No COVID-19 deaths occurred in the mTOR CNI-free group.
Conclusions:
- mTOR-based immunosuppression is non-inferior to standard therapy for COVID-19 outcomes in OHT patients.
- The lack of COVID-19-related deaths in the mTOR CNI-free group suggests a potential protective role warranting further investigation.
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:
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.
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