{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T07:48:58Z","timestamp":1774338538925,"version":"3.50.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aims to evaluate the prevalence, clinical characteristics, severity, mortality, and outcomes of COVID-19 infection in heart transplant recipients, focusing on risk factors for severe disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective, observational study was conducted on adult heart transplant patients (HTxs) at Fuwai Hospital from December 1, 2022, to February 28, 2023, with follow-up until May 30, 2024. Clinical data were collected via telephone surveys and medical records. Logistic regression analyses were conducted to explore risk factors for severe disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 728 of the 916 HTxs were infected with COVID-19 (79.48%); the vaccination rate was 27.95%. Of infected cases, 56.18% were mild, 18.82% moderate, 19.26% severe, and 5.77% critical. Severe disease occurred in 25.00%, with a mortality rate of 4.54%. Logistic regression analyses revealed that age (OR 1.048, 95% CI 1.031-1.066, P&amp;lt;0.001), history of diabetes (OR 1.829, 95% CI 1.221-2.740, P=0.005), Chronic kidney disease stage\u22653 (OR 2.557, 95% CI 1.650-3.963, P&amp;lt;0.001) and immunosuppressive regimens including sirolimus (OR 1.639, 95% CI 1.145-2.348, P=0.007) were independent risk factors for severe infection, while age (OR 1.102, 95% CI 1.053-1.154, P&amp;lt;0.001) and Chronic kidney disease stage\u22653 (OR 6.342, 95% CI 2.980-13.499, P&amp;lt;0.001) were independent risk factors for post-infection mortality. COVID-19 vaccination (OR 0.169, 95% CI 0.039-0.733, P=0.018) was found to be a protective factor against post-infection mortality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>COVID-19 vaccination is recommended for HTxs to reduce severe outcomes and mortality. Sirolimus use was independently associated with severe infection, highlighting the need for careful management of immunosuppression.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1597333","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T04:13:31Z","timestamp":1753848811000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Risk factor analysis and outcomes of heart transplant recipients infected by COVID-19"],"prefix":"10.3389","volume":"16","author":[{"given":"Lin","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sipeng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanshan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenfei","family":"Rao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongkai","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaonan","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoying","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000003670","article-title":"Outcomes of COVID-19 in solid organ transplant recipients: A propensity-matched analysis of a large research network","volume":"105","author":"Hadi","year":"2021","journal-title":"Transplantation"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.2159","article-title":"Characteristics and outcomes of recipients of heart transplant with Coronavirus disease 2019","volume":"5","author":"Latif","year":"2020","journal-title":"JAMA Cardiol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.jchf.2020.10.009","article-title":"COVID-19 in heart transplant recipients: A multicenter analysis of the northern Italian outbreak","volume":"9","author":"Bottio","year":"2021","journal-title":"JACC Heart failure"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2021.05.006","article-title":"Coronavirus disease 2019 in heart transplant recipients: Risk factors, immunosuppression, and outcomes","volume":"40","author":"Genuardi","year":"2021","journal-title":"J Heart Lung Transplant"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2023.09.007","article-title":"Coronavirus disease 2019 outcomes in heart transplant recipients: A large Australian cohort","volume":"43","author":"Cherrett","year":"2024","journal-title":"J Heart Lung Transplant"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2024.03.011","article-title":"Longitudinal outcomes of COVID-19 in solid organ transplant recipients from 2020 to 2023","volume":"24","author":"Solera","year":"2024","journal-title":"Am J Transplant"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000004162","article-title":"COVID-19 clinical outcomes in solid organ transplant recipients during the omicron surge","volume":"106","author":"Cochran","year":"2022","journal-title":"Transplantation"},{"key":"B8","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1002\/hcs2.36","article-title":"Diagnosis and treatment protocol for COVID-19 patients (Tentative 10th Version)","volume":"2","year":"2023","journal-title":"Health Care Sci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15941","article-title":"COVID-19 in solid organ transplant recipients: Initial report from the US epicenter","volume":"20","author":"Pereira","year":"2020","journal-title":"Am J Transplant"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/eurjpc\/zwab175","article-title":"Incidence and prognosis of COVID-19 amongst heart transplant recipients: a systematic review and meta-analysis","volume":"29","author":"Ahmed","year":"2022","journal-title":"Eur J Prev Cardiol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.3780","article-title":"Secondary attack rates for omicron and delta variants of SARS-CoV-2 in Norwegian households","volume":"327","author":"Jorgensen","year":"2022","journal-title":"JAMA"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.4683","article-title":"Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy","volume":"323","author":"Onder","year":"2020","journal-title":"JAMA"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2020.06.016","article-title":"A case series of novel coronavirus infection in heart transplantation from 2 centers in the pandemic area in the North of Italy","volume":"39","author":"Iacovoni","year":"2020","journal-title":"J Heart Lung Transplant"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-020-01722-w","article-title":"COVID-19 among heart transplant recipients in Germany: a multicenter survey","volume":"109","author":"Rivinius","year":"2020","journal-title":"Clin Res Cardiol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2020.05.008","article-title":"Coronavirus disease-2019 in heart transplant recipients in Southeastern Michigan: A case series","volume":"26","author":"Ketcham","year":"2020","journal-title":"J cardiac failure"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s12471-022-01720-9","article-title":"Characteristics and outcomes of COVID-19 in heart transplantation recipients in the Netherlands","volume":"30","author":"Muller","year":"2022","journal-title":"Netherlands Heart J"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.16431","article-title":"Inpatient COVID-19 outcomes in solid organ transplant recipients compared to non-solid organ transplant patients: A retrospective cohort","volume":"21","author":"Avery","year":"2021","journal-title":"Am J Transplant"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1097","article-title":"Coronavirus disease 2019 in solid organ transplant: A multicenter cohort study","volume":"73","author":"Kates","year":"2021","journal-title":"Clin Infect Dis"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00462-7","article-title":"Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study","volume":"399","author":"Nyberg","year":"2022","journal-title":"Lancet"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/ejcts\/ezad229","article-title":"Veno-arterial extracorporeal membrane oxygenation for circulatory failure in COVID-19 patients: insights from the ECMOSARS registry","volume":"64","author":"Anselmi","year":"2023","journal-title":"Eur J cardio-thoracic Surg"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000005134","article-title":"Mortality and hospitalization risk in solid organ transplant patients and SARS-CoV-2-omicron variant","volume":"109","author":"Basharim","year":"2024","journal-title":"Transplantation"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01656-7","article-title":"Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters: pooled analysis of national prospective cohort studies of 30 million individuals in England, Northern Ireland, Scotland, and Wales","volume":"400","author":"Agrawal","year":"2022","journal-title":"Lancet"},{"key":"B23","doi-asserted-by":"publisher","first-page":"112420","DOI":"10.1016\/j.biopha.2021.112420","article-title":"Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets","volume":"145","author":"Farahani","year":"2022","journal-title":"Biomedicine pharmacother = Biomed pharmacotherapie"},{"key":"B24","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1038\/s41421-020-0153-3","article-title":"Network-based drug repurposing for novel coronavirus 2019-nCoV\/SARS-CoV-2","volume":"6","author":"Zhou","year":"2020","journal-title":"Cell discov"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1172\/JCI160766","article-title":"Rapalogs downmodulate intrinsic immunity and promote cell entry of SARS-CoV-2","volume":"132","author":"Shi","year":"2022","journal-title":"J Clin Invest"},{"key":"B26","doi-asserted-by":"publisher","first-page":"108464","DOI":"10.1016\/j.clim.2020.108464","article-title":"Targeting T-cell senescence and cytokine storm with rapamycin to prevent severe progression in COVID-19","volume":"216","author":"Omarjee","year":"2020","journal-title":"Clin Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2099206","article-title":"Neutrophil autophagy and NETosis in COVID-19: perspectives","volume":"19","author":"Zhang","year":"2023","journal-title":"Autophagy"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1876","DOI":"10.1038\/s41467-021-22166-4","article-title":"SARS-CoV-2 infection rewires host cell metabolism and is potentially susceptible to mTORC1 inhibition","volume":"12","author":"Mullen","year":"2021","journal-title":"Nat Commun"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-7568(20)30068-4","article-title":"The potential of rapalogs to enhance resilience against SARS-CoV-2 infection and reduce the severity of COVID-19","volume":"2","author":"Bischof","year":"2021","journal-title":"Lancet Healthy longevity"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.resinv.2023.12.009","article-title":"Safety and efficacy of sirolimus in hospitalised patients with COVID-19 pneumonia","volume":"62","author":"Singla","year":"2024","journal-title":"Respir Invest"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.42006","article-title":"COVID-19 hospitalization in solid organ transplant recipients on immunosuppressive therapy","volume":"6","author":"Kolla","year":"2023","journal-title":"JAMA network Open"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.16155","article-title":"Effects of mTOR inhibitor-related proteinuria on progression of cardiac allograft vasculopathy and outcomes among heart transplant recipients","volume":"21","author":"Asleh","year":"2021","journal-title":"Am J Transpl"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.14228","article-title":"Mtor inhibitors associated with higher cardiovascular adverse events-A large population database analysis","volume":"35","author":"Nguyen","year":"2021","journal-title":"Clin Transpl"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1053\/j.gastro.2020.11.045","article-title":"Protective role of tacrolimus, deleterious role of age and comorbidities in liver transplant recipients with Covid-19: results from the ELITA\/ELTR multi-center European study","volume":"160","author":"Belli","year":"2021","journal-title":"Gastroenterology"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa150","article-title":"Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia","volume":"221","author":"Wang","year":"2020","journal-title":"J Infect Dis"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.46234\/ccdcw2023.070","article-title":"Effectiveness of COVID-19 vaccination against SARS-CoV-2 omicron variant infection and symptoms - China, December 2022-February 2023","volume":"5","author":"Fu","year":"2023","journal-title":"China CDC weekly"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00345-0","article-title":"Vaccine effectiveness of one, two, and three doses of BNT162b2 and CoronaVac against COVID-19 in Hong Kong: a population-based observational study","volume":"22","author":"McMenamin","year":"2022","journal-title":"Lancet Infect diseases"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.17876","article-title":"Association of primary and booster vaccination and prior infection with SARS-CoV-2 infection and severe COVID-19 outcomes","volume":"328","author":"Lin","year":"2022","journal-title":"JAMA"},{"key":"B39","doi-asserted-by":"publisher","first-page":"105547","DOI":"10.1016\/j.jcv.2023.105547","article-title":"Effectiveness of BNT162b2 and Sinovac vaccines against the transmission of SARS-CoV-2 during Omicron-predominance in Hong Kong: A retrospective cohort study of COVID-19 cases","volume":"166","author":"Zhao","year":"2023","journal-title":"J Clin Virol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02219-5","article-title":"Real-world COVID-19 vaccine effectiveness against the Omicron BA.2 variant in a SARS-CoV-2 infection-naive population","volume":"29","author":"Lau","year":"2023","journal-title":"Nat Med"},{"key":"B41","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1186\/s12916-022-02606-8","article-title":"Effectiveness of inactivated and Ad5-nCoV COVID-19 vaccines against SARS-CoV-2 Omicron BA. 2 variant infection, severe illness, and death","volume":"20","author":"Huang","year":"2022","journal-title":"BMC Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.28900","article-title":"Analysis of COVID-19 incidence and severity among adults vaccinated with 2-dose mRNA COVID-19 or inactivated SARS-CoV-2 vaccines with and without boosters in Singapore","volume":"5","author":"Ng","year":"2022","journal-title":"JAMA network Open"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.3390\/vaccines11121845","article-title":"Impact of SARS-CoV-2 infection on humoral and cellular immunity in a cohort of vaccinated solid organ transplant recipients","volume":"11","author":"Ayala-Borges","year":"2023","journal-title":"Vaccines"},{"key":"B44","doi-asserted-by":"publisher","first-page":"755","DOI":"10.3390\/microorganisms11030755","article-title":"Effect of a fourth dose of mRNA vaccine and of immunosuppression in preventing SARS-CoV-2 breakthrough infections in heart transplant patients","volume":"11","author":"Masetti","year":"2023","journal-title":"Microorganisms"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2021.04.003","article-title":"BNT162b2 vaccination in heart transplant recipients: Clinical experience and antibody response","volume":"40","author":"Peled","year":"2021","journal-title":"J Heart Lung Transplant"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2021.07.026","article-title":"SARS-CoV-2 messenger RNA vaccine antibody response and reactogenicity in heart and lung transplant recipients","volume":"40","author":"Hallett","year":"2021","journal-title":"J Heart Lung Transplant"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.16768","article-title":"Cellular and humoral immune response after mRNA-1273 SARS-CoV-2 vaccine in liver and heart transplant recipients","volume":"21","author":"Herrera","year":"2021","journal-title":"Am J Transplant"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-022-02075-2","article-title":"Third dose of the BNT162b2 vaccine in cardiothoracic transplant recipients: predictive factors for humoral response","volume":"112","author":"Costard-Jackle","year":"2023","journal-title":"Clin Res Cardiol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2021.08.010","article-title":"Third dose of the BNT162b2 vaccine in heart transplant recipients: Immunogenicity and clinical experience","volume":"41","author":"Peled","year":"2022","journal-title":"J Heart Lung Transplant"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2022.0670","article-title":"Association of COVID-19 vaccination with risk of COVID-19 infection, hospitalization, and death in heart transplant recipients","volume":"7","author":"Peters","year":"2022","journal-title":"JAMA Cardiol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"107661","DOI":"10.1016\/j.carpath.2024.107661","article-title":"Early, rapidly progressive vasculopathy in a transplanted heart: A possible complication of COVID-19","volume":"72","author":"Pearson","year":"2024","journal-title":"Cardiovasc Pathol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2023.06.003","article-title":"Case report: the challenge for diagnosis of myocarditis and transplant rejection after COVID infection in a heart-transplanted adolescent","volume":"55","author":"Pegado","year":"2023","journal-title":"Transplant Proc"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1111\/tid.14225","article-title":"Rapidly progressive graft vasculopathy in a heart transplant recipient with confirmed SARS-CoV-2 infection","volume":"26","author":"MacKay","year":"2024","journal-title":"Transplant Infect Dis"},{"key":"B54","doi-asserted-by":"publisher","first-page":"2336126","DOI":"10.1080\/0886022X.2024.2336126","article-title":"COVID-19 and renal allograft rejection: insight from controlled and non-controlled studies","volume":"46","author":"Daoud","year":"2024","journal-title":"Renal failure"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1597333\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T04:13:32Z","timestamp":1753848812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1597333\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,30]]},"references-count":54,"alternative-id":["10.3389\/fimmu.2025.1597333"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1597333","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,30]]},"article-number":"1597333"}}