{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T21:39:45Z","timestamp":1789162785596,"version":"build-2803163510"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T00:00:00Z","timestamp":1641427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"NYULH Center for Biospecimen Research and Development, Histology and Immunohistochemistry Laboratory","award":["RRID:SCR_018304"],"award-info":[{"award-number":["RRID:SCR_018304"]}]},{"name":"Laura and Isaac Perlmutter Cancer Center","award":["P30CA016087"],"award-info":[{"award-number":["P30CA016087"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10OD01058"],"award-info":[{"award-number":["S10OD01058"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10OD018338"],"award-info":[{"award-number":["S10OD018338"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may develop end-stage lung disease requiring lung transplantation. We report the clinical course, pulmonary pathology with radiographic correlation, and outcomes after lung transplantation in three patients who developed chronic respiratory failure due to postacute sequelae of SARS-CoV-2 infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective histologic evaluation of explanted lungs due to coronavirus disease 2019 was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>None of the patients had known prior pulmonary disease. The major pathologic findings in the lung explants were proliferative and fibrotic phases of diffuse alveolar damage, interstitial capillary neoangiogenesis, and mononuclear inflammation, specifically macrophages, with varying numbers of T and B lymphocytes. The fibrosis varied from early collagen deposition to more pronounced interstitial collagen deposition; however, pulmonary remodeling with honeycomb change was not present. Other findings included peribronchiolar metaplasia, microvascular thrombosis, recanalized thrombi in muscular arteries, and pleural adhesions. No patients had either recurrence of SARS-CoV-2 infection or allograft rejection following transplant at this time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The major pathologic findings in the lung explants of patients with SARS-CoV-2 infection suggest ongoing fibrosis, prominent macrophage infiltration, neoangiogenesis, and microvascular thrombosis. Characterization of pathologic findings could help develop novel management strategies.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ajcp\/aqab208","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T20:14:17Z","timestamp":1637007257000},"page":"908-926","source":"Crossref","is-referenced-by-count":22,"title":["Pulmonary Pathology of End-Stage COVID-19 Disease in Explanted Lungs and Outcomes After Lung Transplantation"],"prefix":"10.1093","volume":"157","author":[{"given":"Abdallah","family":"Flaifel","sequence":"first","affiliation":[{"name":"Departments of Pathology, NYU Langone Medical Center, New York University School of Medicine , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Kwok","sequence":"additional","affiliation":[{"name":"Medicine, NYU Langone Medical Center, New York University School of Medicine , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Ko","sequence":"additional","affiliation":[{"name":"Radiology, NYU Langone Medical Center, New York University School of Medicine , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6254-7832","authenticated-orcid":false,"given":"Stephanie","family":"Chang","sequence":"additional","affiliation":[{"name":"Cardiothoracic Surgery, NYU Langone Medical Center, New York University School of Medicine , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deane","family":"Smith","sequence":"additional","affiliation":[{"name":"Cardiothoracic Surgery, NYU Langone Medical Center, New York University School of Medicine , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5542-2994","authenticated-orcid":false,"given":"Fang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Departments of Pathology, NYU Langone Medical Center, New York University School of Medicine , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2028-6873","authenticated-orcid":false,"given":"Luis A","family":"Chiriboga","sequence":"additional","affiliation":[{"name":"Departments of Pathology, NYU Langone Medical Center, New York University School of Medicine , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Briana","family":"Zeck","sequence":"additional","affiliation":[{"name":"Departments of Pathology, NYU Langone Medical Center, New York University School of Medicine , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Theise","sequence":"additional","affiliation":[{"name":"Departments of Pathology, NYU Langone Medical Center, New York University School of Medicine , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darya","family":"Rudym","sequence":"additional","affiliation":[{"name":"Medicine, NYU Langone Medical Center, New York University School of Medicine , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Lesko","sequence":"additional","affiliation":[{"name":"Medicine, NYU Langone Medical Center, New York University School of Medicine , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Angel","sequence":"additional","affiliation":[{"name":"Medicine, NYU Langone Medical Center, New York University School of Medicine , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Moreira","sequence":"additional","affiliation":[{"name":"Departments of Pathology, NYU Langone Medical Center, New York University School of Medicine , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navneet","family":"Narula","sequence":"additional","affiliation":[{"name":"Departments of Pathology, NYU Langone Medical Center, New York University School of Medicine , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,6]]},"reference":[{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1001\/jama.2020.6775","article-title":"Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area","volume":"323","author":"Richardson","year":"2020","journal-title":"JAMA."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1056\/NEJMoa2007764","article-title":"Remdesivir for the treatment of Covid-19\u2014preliminary report. Reply","volume":"383","author":"Beigel","year":"2020","journal-title":"N Engl J Med."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1056\/NEJMoa2021436","article-title":"Dexamethasone in hospitalized patients with Covid-19","volume":"384","author":"RECOVERY Collaborative Group","year":"2021","journal-title":"N Engl J Med"},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"190132","DOI":"10.1183\/16000617.0132-2019","article-title":"Developments in lung transplantation over the past decade","volume":"29","author":"van der Mark","year":"2020","journal-title":"Eur Respir Rev."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"eabe4282","DOI":"10.1126\/scitranslmed.abe4282","article-title":"Lung transplantation for patients with severe COVID-19","volume":"12","author":"Bharat","year":"2020","journal-title":"Sci Transl Med."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1097\/CM9.0000000000000839","article-title":"Lung transplantation as therapeutic option in acute respiratory distress syndrome for coronavirus disease 2019\u2013related pulmonary fibrosis","volume":"133","author":"Chen","year":"2020","journal-title":"Chin Med J (Engl)."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/S2213-2600(20)30393-3","article-title":"When to consider lung transplantation for COVID-19","volume":"8","author":"Cypel","year":"2020","journal-title":"Lancet Respir Med."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1093\/ajcp\/aqaa264","article-title":"Pulmonary pathology of COVID-19 following 8 weeks to 4 months of severe disease: a report of three cases, including one with bilateral lung transplantation","volume":"155","author":"Aesif","year":"2021","journal-title":"Am J Clin Pathol."},{"key":"2023031812463957500_","article-title":"The pulmonary pathology of COVID-19 [published online September 23, 2020]","author":"Arrossi","journal-title":"Cleve Clin J Med."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1056\/NEJMoa2015432","article-title":"Pulmonary vascular pathology in Covid-19: reply","volume":"383","author":"Ackermann","year":"2020","journal-title":"N Engl J Med."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1093\/ajcp\/aqaa156","article-title":"Forty postmortem examinations in COVID-19 patients","volume":"154","author":"De Michele","year":"2020","journal-title":"Am J Clin Pathol."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1038\/s41379-020-00661-1","article-title":"COVID-19 pulmonary pathology: a multi-institutional autopsy cohort from Italy and New York City","volume":"33","author":"Borczuk","year":"2020","journal-title":"Mod Pathol."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"e000155","DOI":"10.1136\/jitc-2019-000155","article-title":"The Society for Immunotherapy in Cancer statement on best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) staining and validation","volume":"8","author":"Taube","year":"2020","journal-title":"J Immunother Cancer."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/s42003-021-01962-0","article-title":"Evidence for continuity of interstitial spaces across tissue and organ boundaries in humans","volume":"4","author":"Cenaj","year":"2021","journal-title":"Commun Biol."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/labinvest.2016.115","article-title":"Covalently deposited dyes: a new chromogen paradigm that facilitates analysis of multiple biomarkers in situ","volume":"97","author":"Day","year":"2017","journal-title":"Lab Invest."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"E2","DOI":"10.1038\/s41586-021-03921-5","article-title":"Author correction: a molecular single-cell lung atlas of lethal COVID-19","volume":"598","author":"Melms","year":"2021","journal-title":"Nature."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"e202000955","DOI":"10.26508\/lsa.202000955","article-title":"Profiling of immune dysfunction in COVID-19 patients allows early prediction of disease progression","volume":"4","author":"Rendeiro","year":"2021","journal-title":"Life Sci Alliance."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/s41586-021-03475-6","article-title":"The spatial landscape of lung pathology during COVID-19 progression","volume":"593","author":"Rendeiro","year":"2021","journal-title":"Nature."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1136\/thoraxjnl-2014-206420","article-title":"Streptococcus pneumoniae triggers progression of pulmonary fibrosis through pneumolysin","volume":"70","author":"Knippenberg","year":"2015","journal-title":"Thorax."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"106239","DOI":"10.1016\/j.rmed.2020.106239","article-title":"Pulmonary pathology of ARDS in COVID-19: a pathological review for clinicians","volume":"176","author":"Batah","year":"2021","journal-title":"Respir Med."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1097\/MCP.0000000000000761","article-title":"Pulmonary pathology of COVID-19: a review of autopsy studies","volume":"27","author":"Borczuk","year":"2021","journal-title":"Curr Opin Pulm Med."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S2213-2600(21)00077-1","article-title":"Early outcomes after lung transplantation for severe COVID-19: a series of the first consecutive cases from four countries","volume":"9","author":"Bharat","year":"2021","journal-title":"Lancet Respir Med."},{"key":"2023031812463957500_","first-page":"2557","article-title":"Pulmonary fibrosis in the aftermath of the COVID-19 era (review)","volume":"20","author":"Vasarmidi","year":"2020","journal-title":"Exp Ther Med."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/s41422-021-00523-8","article-title":"A cohort autopsy study defines COVID-19 systemic pathogenesis","volume":"31","author":"Yao","year":"2021","journal-title":"Cell Res."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1097\/00000542-199604000-00002","article-title":"Histopathologic and microbiologic aspects of ventilator-associated pneumonia","volume":"84","author":"F\u00e0bregas","year":"1996","journal-title":"Anesthesiology."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"C987","DOI":"10.1152\/ajpcell.00321.2013","article-title":"Cellular mechanisms of tissue fibrosis: 7. New insights into the cellular mechanisms of pulmonary fibrosis","volume":"306","author":"Barkauskas","year":"2014","journal-title":"Am J Physiol Cell Physiol."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3390\/medicina55040083","article-title":"Epithelial-mesenchymal transition in the pathogenesis of idiopathic pulmonary fibrosis","volume":"55","author":"Salton","year":"2019","journal-title":"Medicina (Kaunas)."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1164\/rccm.200905-0798OC","article-title":"Latent herpesvirus infection augments experimental pulmonary fibrosis","volume":"181","author":"Vannella","year":"2010","journal-title":"Am J Respir Crit Care Med."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"eabf8396","DOI":"10.1126\/scitranslmed.abf8396","article-title":"COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters","volume":"13","author":"de Melo","year":"2021","journal-title":"Sci Transl Med."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1183\/09059180.00004413","article-title":"Tissue remodelling in chronic bronchial diseases: from the epithelial to mesenchymal phenotype","volume":"23","author":"Pain","year":"2014","journal-title":"Eur Respir Rev."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/S0002-9440(10)64282-4","article-title":"Aberrant Wnt\/beta-catenin pathway activation in idiopathic pulmonary fibrosis","volume":"162","author":"Chilosi","year":"2003","journal-title":"Am J Pathol."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1111\/resp.12112","article-title":"Adult stem cells for chronic lung diseases","volume":"18","author":"Mora","year":"2013","journal-title":"Respirology."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"4236973","DOI":"10.1155\/2019\/4236973","article-title":"Mesenchymal stem cell-based therapy of inflammatory lung diseases: current understanding and future perspectives","volume":"2019","author":"Harrell","year":"2019","journal-title":"Stem Cells Int."},{"key":"2023031812463957500_","first-page":"285","article-title":"Feasibility of mesenchymal stem cell therapy for COVID-19: a mini review","volume":"20","author":"Li","year":"2020","journal-title":"Curr Gene Ther."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1056\/NEJMoa2015432","article-title":"Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19","volume":"383","author":"Ackermann","year":"2020","journal-title":"N Engl J Med."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.yexmp.2015.07.011","article-title":"The anti-fibrotic effects of microRNA-153 by targeting TGFBR-2 in pulmonary fibrosis","volume":"99","author":"Liang","year":"2015","journal-title":"Exp Mol Pathol."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s12272-021-01331-9","article-title":"COVID-19 and pulmonary fibrosis: therapeutics in clinical trials, repurposing, and potential development","volume":"44","author":"Yim","year":"2021","journal-title":"Arch Pharm Res."},{"key":"2023031812463957500_","first-page":"85","article-title":"Combined pirfenidone, azithromycin and prednisolone in post-H1N1 ARDS pulmonary fibrosis","volume":"35","author":"Saha","year":"2018","journal-title":"Sarcoidosis Vasc Diffuse Lung Dis."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0272-5231(05)70158-1","article-title":"Pulmonary pathology of acute respiratory distress syndrome","volume":"21","author":"Tomashefski","year":"2000","journal-title":"Clin Chest Med."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/s41586-021-03475-6","article-title":"The spatial landscape of lung pathology during COVID-19 progression","volume":"593","author":"Rendeiro","year":"2021","journal-title":"Nature."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1165\/rcmb.2012-0090OC","article-title":"Pulmonary macrophage subpopulations in the induction and resolution of acute lung injury","volume":"47","author":"Johnston","year":"2012","journal-title":"Am J Respir Cell Mol Biol."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"58","DOI":"10.3164\/jcbn.17-111","article-title":"Pirfenidone suppresses polarization to M2 phenotype macrophages and the fibrogenic activity of rat lung fibroblasts","volume":"63","author":"Toda","year":"2018","journal-title":"J Clin Biochem Nutr."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.molimm.2018.05.003","article-title":"Pirfenidone ameliorates lipopolysaccharide-induced pulmonary inflammation and fibrosis by blocking NLRP3 inflammasome activation","volume":"99","author":"Li","year":"2018","journal-title":"Mol Immunol."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"3124","DOI":"10.1016\/j.jacc.2019.10.036","article-title":"Transition of macrophages to fibroblast-like cells in healing myocardial infarction","volume":"74","author":"Haider","year":"2019","journal-title":"J Am Coll Cardiol."},{"key":"2023031812463957500_","doi-asserted-by":"crossref","first-page":"e2495","DOI":"10.1038\/cddis.2016.402","article-title":"Inflammatory macrophages can transdifferentiate into myofibroblasts during renal fibrosis","volume":"7","author":"Meng","year":"2016","journal-title":"Cell Death Dis."}],"container-title":["American Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajcp\/article-pdf\/157\/6\/908\/49558503\/aqab208.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajcp\/article-pdf\/157\/6\/908\/49558503\/aqab208.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,12]],"date-time":"2023-11-12T17:28:09Z","timestamp":1699810089000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajcp\/article\/157\/6\/908\/6499165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,6]]},"references-count":45,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,1,6]]},"published-print":{"date-parts":[[2022,6,7]]}},"URL":"https:\/\/doi.org\/10.1093\/ajcp\/aqab208","relation":{},"ISSN":["0002-9173","1943-7722"],"issn-type":[{"value":"0002-9173","type":"print"},{"value":"1943-7722","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,6,1]]},"published":{"date-parts":[[2022,1,6]]}}}