{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:32:59Z","timestamp":1790865179992,"version":"4.1.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:00:00Z","timestamp":1698969600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:00:00Z","timestamp":1698969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Free State of Bavaria, Germany","award":["BayVOC"],"award-info":[{"award-number":["BayVOC"]}]},{"name":"Free State of Bavaria, Germany","award":["BayVOC"],"award-info":[{"award-number":["BayVOC"]}]},{"DOI":"10.13039\/501100005722","name":"Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005722","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Infection"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Lung transplant recipients are at increased risk of severe disease following infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) due to high-dose immunosuppressive drugs and the lung is the main organ affected by Coronavirus disease 2019 (COVID-19). Several studies have confirmed increased SARS-CoV-2-related mortality and morbidity in patients living with lung allografts; however, detailed immunological studies of patients with SARS-CoV-2 infection in the early phase following transplantation remain scarce.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We investigated patients who were infected with SARS-CoV-2 in the early phase (18\u2013103\u00a0days) after receiving double-lung allografts (<jats:italic>n<\/jats:italic>\u2009=\u20094, LuTx) in comparison to immunocompetent patients who had not received solid organ transplants (<jats:italic>n<\/jats:italic>\u2009=\u200988, noTx). We analyzed SARS-CoV-2-specific antibody responses against the SARS-CoV-2 spike and nucleocapsid proteins using enzyme-linked immunosorbent assays (ELISA), chemiluminescence immunoassays (CLIA), and immunoblot assays. T cell responses were investigated using Elispot assays.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>One LuTx patient suffered from persistent infection with fatal outcome 122\u00a0days post-infection despite multiple interventions including remdesivir, convalescent plasma, and the monoclonal antibody bamlanivimab. Two patients experienced clinically mild disease with prolonged viral shedding (47 and 79\u00a0days), and one patient remained asymptomatic. Antibody and T cell responses were significantly reduced or undetectable in all LuTx patients compared to noTx patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Patients in the early phase following lung allograft transplantation are vulnerable to infection with SARS-CoV-2 due to impaired immune responses. This patient population should be vaccinated before LuTx, protected from infection post\u2013LuTx, and in case of infection treated generously with currently available interventions.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s15010-023-02116-6","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T11:01:38Z","timestamp":1699009298000},"page":"847-855","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Impaired immune responses and prolonged viral replication in lung allograft recipients infected with SARS-CoV-2 in the early phase after transplantation"],"prefix":"10.1007","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2380-4223","authenticated-orcid":false,"given":"Olaf M.","family":"Glueck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0572-5188","authenticated-orcid":false,"given":"Xiaoling","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6629-3542","authenticated-orcid":false,"given":"Irina","family":"Badell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0942-0637","authenticated-orcid":false,"given":"Paul R.","family":"Wratil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Graf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Krebs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Blum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8409-3037","authenticated-orcid":false,"given":"Johannes C.","family":"Hellmuth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Scherer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Hollaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia M.","family":"Spaeth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burak","family":"Karakoc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thimo","family":"Fuchs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Zimmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Kauke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Moosmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver T.","family":"Keppler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7016-0470","authenticated-orcid":false,"given":"Maximilian","family":"Muenchhoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,3]]},"reference":[{"key":"2116_CR1","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1111\/ajt.14208","volume":"17","author":"JA Fishman","year":"2017","unstructured":"Fishman JA. Infection in organ transplantation. Am J Transplant. 2017;17:856\u201379.","journal-title":"Am J Transplant"},{"key":"2116_CR2","first-page":"741","volume":"11","author":"P Hernandez Mdel","year":"2015","unstructured":"Hernandez Mdel P, Martin P, Simkins J. Infectious complications after liver transplantation. Gastroenterol Hepatol (N Y). 2015;11:741\u201353.","journal-title":"Gastroenterol Hepatol (N Y)"},{"key":"2116_CR3","doi-asserted-by":"publisher","first-page":"e00042\u201319","DOI":"10.1128\/CMR.00042-19","volume":"32","author":"MG Ison","year":"2019","unstructured":"Ison MG, Hirsch HH. Community-acquired respiratory viruses in transplant patients: diversity, impact, unmet clinical needs. Clin Microbiol Rev. 2019;32:e00042\u201319.","journal-title":"Clin Microbiol Rev."},{"key":"2116_CR4","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.13511","volume":"33","author":"O Manuel","year":"2019","unstructured":"Manuel O, Estabrook M, P. American Society of Transplantation Infectious Diseases Community of. RNA respiratory viral infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33: e13511.","journal-title":"Clin Transplant"},{"key":"2116_CR5","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1034\/j.1600-6143.2002.20315.x","volume":"2","author":"RA Vilchez","year":"2002","unstructured":"Vilchez RA, et al. Influenza virus infection in adult solid organ transplant recipients. Am J Transplant. 2002;2:287\u201391.","journal-title":"Am J Transplant"},{"key":"2116_CR6","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1097\/MOT.0000000000000663","volume":"24","author":"HH Nam","year":"2019","unstructured":"Nam HH, Ison MG. Community-acquired respiratory viruses in solid organ transplant. Curr Opin Organ Transplant. 2019;24:483\u20139.","journal-title":"Curr Opin Organ Transplant"},{"key":"2116_CR7","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1111\/j.1365-2249.2005.02671.x","volume":"139","author":"G Hodge","year":"2005","unstructured":"Hodge G, et al. Intracellular cytokines in blood T cells in lung transplant patients\u2013a more relevant indicator of immunosuppression than drug levels. Clin Exp Immunol. 2005;139:159\u201364.","journal-title":"Clin Exp Immunol"},{"key":"2116_CR8","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1111\/j.1365-2249.2010.04186.x","volume":"161","author":"G Hodge","year":"2010","unstructured":"Hodge G, et al. Time post-lung transplant correlates with increasing peripheral blood T cell granzyme B and proinflammatory cytokines. Clin Exp Immunol. 2010;161:584\u201390.","journal-title":"Clin Exp Immunol"},{"key":"2116_CR9","doi-asserted-by":"publisher","first-page":"2477","DOI":"10.1097\/TP.0000000000001685","volume":"101","author":"DA van Kessel","year":"2017","unstructured":"van Kessel DA, et al. Long-term follow-up of humoral immune status in adult lung transplant recipients. Transplantation. 2017;101:2477\u201383.","journal-title":"Transplantation"},{"key":"2116_CR10","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.1093\/cid\/cix1082","volume":"66","author":"Y Natori","year":"2018","unstructured":"Natori Y, et al. A double-blind, randomized trial of high-dose vs standard-dose influenza vaccine in adult solid-organ transplant recipients. Clin Infect Dis. 2018;66:1698\u2013704.","journal-title":"Clin Infect Dis"},{"key":"2116_CR11","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1164\/rccm.202109-2026LE","volume":"205","author":"V Gerovasili","year":"2022","unstructured":"Gerovasili V, et al. Impaired humoral and cellular responses to COVID-19 vaccine in heart and lung transplant recipients. Am J Respir Crit Care Med. 2022;205:1476\u20139.","journal-title":"Am J Respir Crit Care Med"},{"key":"2116_CR12","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1007\/s00392-021-01880-5","volume":"110","author":"R Schramm","year":"2021","unstructured":"Schramm R, et al. Poor humoral and T-cell response to two-dose SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients. Clin Res Cardiol. 2021;110:1142\u20139.","journal-title":"Clin Res Cardiol"},{"key":"2116_CR13","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1007\/s15010-022-01914-8","volume":"51","author":"N Kneidinger","year":"2023","unstructured":"Kneidinger N, et al. Outcome of lung transplant recipients infected with SARS-CoV-2\/Omicron\/B.1.1.529: a Nationwide German study. Infection. 2023;51:749\u201357.","journal-title":"Infection"},{"key":"2116_CR14","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1111\/ajt.14042","volume":"17","author":"M Peghin","year":"2017","unstructured":"Peghin M, et al. Epidemiology and immediate indirect effects of respiratory viruses in lung transplant recipients: a 5-year prospective study. Am J Transplant. 2017;17:1304\u201312.","journal-title":"Am J Transplant"},{"key":"2116_CR15","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1111\/ajt.15944","volume":"20","author":"OS Kates","year":"2020","unstructured":"Kates OS, et al. Earliest cases of coronavirus disease 2019 (COVID-19) identified in solid organ transplant recipients in the United States. Am J Transplant. 2020;20:1885\u201390.","journal-title":"Am J Transplant"},{"key":"2116_CR16","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1097\/TP.0000000000003508","volume":"105","author":"J Messika","year":"2021","unstructured":"Messika J, et al. COVID-19 in lung transplant recipients. Transplantation. 2021;105:177\u201386.","journal-title":"Transplantation"},{"key":"2116_CR17","doi-asserted-by":"publisher","first-page":"1816","DOI":"10.1111\/ajt.16364","volume":"21","author":"B Saez-Gimenez","year":"2021","unstructured":"Saez-Gimenez B, et al. COVID-19 in lung transplant recipients: a multicenter study. Am J Transplant. 2021;21:1816\u201324.","journal-title":"Am J Transplant"},{"key":"2116_CR18","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1016\/j.transproceed.2021.12.014","volume":"54","author":"J Zimmermann","year":"2022","unstructured":"Zimmermann J, et al. COVID-19 in recent lung transplant recipients: clinical outcomes and management strategies. Transplant Proc. 2022;54:1504\u201316.","journal-title":"Transplant Proc"},{"key":"2116_CR19","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/s00430-021-00719-0","volume":"210","author":"A Osterman","year":"2021","unstructured":"Osterman A, et al. Comparison of four commercial, automated antigen tests to detect SARS-CoV-2 variants of concern. Med Microbiol Immunol. 2021;210:263\u201375.","journal-title":"Med Microbiol Immunol"},{"issue":"43","key":"2116_CR20","doi-asserted-by":"publisher","first-page":"2002066","DOI":"10.2807\/1560-7917.ES.2021.26.43.2002066","volume":"26","author":"M Muenchhoff","year":"2021","unstructured":"Muenchhoff M, et al. Genomic epidemiology reveals multiple introductions of SARS-CoV-2 followed by community and nosocomial spread, Germany, February to May 2020. Euro Surveill. 2021;26(43):2002066.","journal-title":"Euro Surveill."},{"issue":"7","key":"2116_CR21","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.1111\/ajt.15929","volume":"20","author":"M Fernandez-Ruiz","year":"2020","unstructured":"Fernandez-Ruiz M, et al. COVID-19 in solid organ transplant recipients: A single-center case series from Spain. Am J Transplant. 2020;20(7):1849\u201358.","journal-title":"Am J Transplant"},{"key":"2116_CR22","doi-asserted-by":"publisher","first-page":"1800","DOI":"10.1111\/ajt.15941","volume":"20","author":"MR Pereira","year":"2020","unstructured":"Pereira MR, et al. COVID-19 in solid organ transplant recipients: Initial report from the US epicenter. Am J Transplant. 2020;20:1800\u20138.","journal-title":"Am J Transplant"},{"key":"2116_CR23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0247461","volume":"16","author":"A Booth","year":"2021","unstructured":"Booth A, et al. Population risk factors for severe disease and mortality in COVID-19: a global systematic review and meta-analysis. PLoS ONE. 2021;16: e0247461.","journal-title":"PLoS ONE"},{"key":"2116_CR24","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1186\/s12879-021-06536-3","volume":"21","author":"ZG Dessie","year":"2021","unstructured":"Dessie ZG, Zewotir T. Mortality-related risk factors of COVID-19: a systematic review and meta-analysis of 42 studies and 423,117 patients. BMC Infect Dis. 2021;21:855.","journal-title":"BMC Infect Dis"},{"key":"2116_CR25","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s15010-020-01509-1","volume":"49","author":"D Wolff","year":"2021","unstructured":"Wolff D, et al. Risk factors for Covid-19 severity and fatality: a structured literature review. Infection. 2021;49:15\u201328.","journal-title":"Infection"},{"key":"2116_CR26","doi-asserted-by":"publisher","first-page":"e283","DOI":"10.1016\/S2666-5247(21)00068-9","volume":"2","author":"S Jangra","year":"2021","unstructured":"Jangra S, et al. SARS-CoV-2 spike E484K mutation reduces antibody neutralisation. Lancet Microbe. 2021;2:e283\u20134.","journal-title":"Lancet Microbe"},{"key":"2116_CR27","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1038\/s41591-021-01386-7","volume":"27","author":"EM Bange","year":"2021","unstructured":"Bange EM, et al. CD8(+) T cells contribute to survival in patients with COVID-19 and hematologic cancer. Nat Med. 2021;27:1280\u20139.","journal-title":"Nat Med"},{"key":"2116_CR28","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/s41590-021-01122-w","volume":"23","author":"P Moss","year":"2022","unstructured":"Moss P. The T cell immune response against SARS-CoV-2. Nat Immunol. 2022;23:186\u201393.","journal-title":"Nat Immunol"},{"key":"2116_CR29","doi-asserted-by":"publisher","first-page":"9318","DOI":"10.1128\/JVI.01049-10","volume":"84","author":"J Zhao","year":"2010","unstructured":"Zhao J, Zhao J, Perlman S. T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice. J Virol. 2010;84:9318\u201325.","journal-title":"J Virol"},{"key":"2116_CR30","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1182\/blood.2021012248","volume":"140","author":"AAR Tobian","year":"2022","unstructured":"Tobian AAR, Cohn CS, Shaz BH. COVID-19 convalescent plasma. Blood. 2022;140:196\u2013207.","journal-title":"Blood"},{"key":"2116_CR31","doi-asserted-by":"publisher","first-page":"2012","DOI":"10.1038\/s41591-021-01488-2","volume":"27","author":"P Begin","year":"2021","unstructured":"Begin P, et al. Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial. Nat Med. 2021;27:2012\u201324.","journal-title":"Nat Med"},{"key":"2116_CR32","volume-title":"SARS-CoV-2 variant mutations conferring reducedsusceptibility to antiviral drugs and monoclonal antibodies: a non-systematic literature review for surveillance purposes\u2014July 2023","author":"European Centre for Disease Prevention and Control","year":"2023","unstructured":"European Centre for Disease Prevention and Control. SARS-CoV-2 variant mutations conferring reducedsusceptibility to antiviral drugs and monoclonal antibodies: a non-systematic literature review for surveillance purposes\u2014July 2023. Stockholm: ECDC; 2023."}],"container-title":["Infection"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s15010-023-02116-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s15010-023-02116-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s15010-023-02116-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T17:04:01Z","timestamp":1717175041000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s15010-023-02116-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,3]]},"references-count":32,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["2116"],"URL":"https:\/\/doi.org\/10.1007\/s15010-023-02116-6","relation":{},"ISSN":["0300-8126","1439-0973"],"issn-type":[{"value":"0300-8126","type":"print"},{"value":"1439-0973","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,3]]},"assertion":[{"value":"26 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no competing interests to declare that are relevant to the content of this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was approved by the local ethics committee (Institutional Review Board) (No: 20-245). Furthermore, all patients were recruited into the COVID-19 Registry of the LMU University Hospital Munich (CORKUM) under the WHO trial ID DRKS00021225. All patients gave their written consent to participate in this study and for any resulting publication. This study was conducted following the guidelines of the declaration of Helsinki and the Rules of Good Scientific Practice (GSP) of the Ludwig Maximilian University Munich.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}