{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:49:00Z","timestamp":1792900140937,"version":"4.5.0"},"reference-count":49,"publisher":"European Respiratory Society (ERS)","issue":"4","license":[{"start":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T00:00:00Z","timestamp":1647475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2022,2,13]]},"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:p>Some patients experience pulmonary sequelae after SARS-CoV-2 infection, ranging from self-limited abnormalities to major lung diseases. Morphological analysis of lung tissue may help our understanding of pathogenic mechanisms and help to provide consistent personalised management. The aim of this study was to ascertain morphological and immunomolecular features of lung tissue. Transbronchial lung cryobiopsy was carried out in patients with persistent symptoms and computed tomography suggestive of residual lung disease after recovery from SARS-CoV-2 infection. 164 patients were referred for suspected pulmonary sequelae after COVID-19; 10 patients with &gt;5% parenchymal lung disease underwent lung biopsy. The histological pattern of lung disease was not homogeneous and three different case clusters could be identified, which was mirrored by their clinical and radiological features. Cluster 1 (\u201cchronic fibrosing\u201d) was characterised by post-infection progression of pre-existing interstitial pneumonias. Cluster 2 (\u201cacute\/subacute injury\u201d) was characterised by different types and grades of lung injury, ranging from organising pneumonia and fibrosing nonspecific interstitial pneumonia to diffuse alveolar damage. Cluster 3 (\u201cvascular changes\u201d) was characterised by diffuse vascular increase, dilatation and distortion (capillaries and venules) within otherwise normal parenchyma. Clusters 2 and 3 had immunophenotypical changes similar to those observed in early\/mild COVID-19 pneumonias (abnormal expression of STAT3 in hyperplastic pneumocytes and PD-L1, IDO and STAT3 in endothelial cells). This is the first study correlating histological\/immunohistochemical patterns with clinical and radiological pictures of patients with post-COVID lung disease. Different phenotypes with potentially different underlying pathogenic mechanisms have been identified.<\/jats:p>","DOI":"10.1183\/13993003.02411-2021","type":"journal-article","created":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T15:50:17Z","timestamp":1647532217000},"page":"2102411","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":84,"title":["Clinical, radiological and pathological findings in patients with persistent lung disease following SARS-CoV-2 infection"],"prefix":"10.1183","volume":"60","author":[{"given":"Claudia","family":"Ravaglia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Doglioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Chilosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6608-0574","authenticated-orcid":false,"given":"Sara","family":"Piciucchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Dubini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0168-4718","authenticated-orcid":false,"given":"Federica","family":"Pedica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Puglisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Donati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4781-6539","authenticated-orcid":false,"given":"Sara","family":"Tomassetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venerino","family":"Poletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2022,3,17]]},"reference":[{"key":"2024102102542890000_60.4.2102411.1","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.cmi.2021.03.012","article-title":"Persistent COVID-19 symptoms are highly prevalent 6\u2005months after hospitalization: results from a large prospective cohort","volume":"27","author":"Ghosn","year":"2021","journal-title":"Clin Microbiol Infect"},{"key":"2024102102542890000_60.4.2102411.2","doi-asserted-by":"crossref","first-page":"E216","DOI":"10.1148\/radiol.2021204482","article-title":"Interstitial lung disease after COVID-19 infection: a catalog of uncertainties","volume":"299","author":"Wells","year":"2021","journal-title":"Radiology"},{"key":"2024102102542890000_60.4.2102411.3","doi-asserted-by":"crossref","first-page":"E177","DOI":"10.1148\/radiol.2021203153","article-title":"Six-month follow-up chest CT findings after severe COVID-19 pneumonia","volume":"299","author":"Han","year":"2021","journal-title":"Radiology"},{"key":"2024102102542890000_60.4.2102411.4","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.ijid.2021.07.016","article-title":"Long-term clinical follow up of patients suffering from moderate to severe COVID-19 infection: a monocentric prospective observational cohort study","volume":"109","author":"Darcis","year":"2021","journal-title":"Int J Infect Dis"},{"key":"2024102102542890000_60.4.2102411.5","doi-asserted-by":"publisher","DOI":"10.7326\/M21-0878"},{"key":"2024102102542890000_60.4.2102411.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2021.06.009"},{"key":"2024102102542890000_60.4.2102411.7","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1007\/s40121-021-00461-3","article-title":"Long-term patient-centred follow-up in a prospective cohort of patients with COVID-19","volume":"10","author":"Righi","year":"2021","journal-title":"Infect Dis Ther"},{"key":"2024102102542890000_60.4.2102411.8","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1016\/j.cmi.2021.05.033","article-title":"Post-COVID-19 symptoms 6\u2005months after acute infection among hospitalized and non-hospitalized patients","volume":"27","author":"Peghin","year":"2021","journal-title":"Clin Microbiol Infect"},{"key":"2024102102542890000_60.4.2102411.9","doi-asserted-by":"crossref","first-page":"e2111417","DOI":"10.1001\/jamanetworkopen.2021.11417","article-title":"Assessment of the frequency and variety of persistent symptoms among patients with COVID-19: a systematic review","volume":"4","author":"Nasserie","year":"2021","journal-title":"JAMA Netw Open"},{"key":"2024102102542890000_60.4.2102411.10","doi-asserted-by":"crossref","first-page":"100122","DOI":"10.1016\/j.lanepe.2021.100122","article-title":"Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study","volume":"6","author":"Augustin","year":"2021","journal-title":"Lancet Reg Health Eur"},{"key":"2024102102542890000_60.4.2102411.11","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/s41584-021-00608-z","article-title":"Systemic and organ-specific immune-related manifestations of COVID-19","volume":"17","author":"Ramos-Casals","year":"2021","journal-title":"Nat Rev Rheumatol"},{"key":"2024102102542890000_60.4.2102411.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01283-z"},{"key":"2024102102542890000_60.4.2102411.13","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01090-2021"},{"key":"2024102102542890000_60.4.2102411.14","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12890-019-0780-3","article-title":"Diagnostic yield and risk\/benefit analysis of trans-bronchial lung cryobiopsy in diffuse parenchymal lung diseases: a large cohort of 699 patients","volume":"19","author":"Ravaglia","year":"2019","journal-title":"BMC Pulm Med"},{"key":"2024102102542890000_60.4.2102411.15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086716"},{"key":"2024102102542890000_60.4.2102411.16","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1159\/000514822","article-title":"COVID-19 interstitial pneumonia: histological and immunohistochemical features on cryobiopsies","volume":"100","author":"Doglioni","year":"2021","journal-title":"Respiration"},{"key":"2024102102542890000_60.4.2102411.17","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1038\/s41379-021-00808-8","article-title":"The pathogenic role of epithelial and endothelial cells in early-phase COVID-19 pneumonia: victims and partners in crime","volume":"34","author":"Chilosi","year":"2021","journal-title":"Mod Pathol"},{"key":"2024102102542890000_60.4.2102411.18","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.1016\/S2213-2600(21)00554-3","article-title":"Awake prone positioning for COVID-19 acute respiratory failure: imaging and histological background","volume":"10","author":"Piciucchi","year":"2022","journal-title":"Lancet Respir Med"},{"key":"2024102102542890000_60.4.2102411.19","doi-asserted-by":"crossref","unstructured":"Chilosi M , Marcolini L , Cali\u00f2 A , et al. Immunohistochemistry and molecular biology in transbronchial cryobiopsies. In: Poletti V , ed. Transbronchial Cryobiopsy in Diffuse Parenchymal Lung Disease. London, Springer, 2019; pp. 81\u2013102.","DOI":"10.1007\/978-3-030-14891-1_9"},{"key":"2024102102542890000_60.4.2102411.20","doi-asserted-by":"crossref","first-page":"27","DOI":"10.5858\/134.1.27","article-title":"Respiratory bronchiolitis\/interstitial lung disease: fibrosis, pulmonary function, and evolving concepts","volume":"134","author":"Churg","year":"2010","journal-title":"Arch Pathol Lab Med"},{"key":"2024102102542890000_60.4.2102411.21","doi-asserted-by":"crossref","first-page":"106201","DOI":"10.1016\/j.rmed.2020.106201","article-title":"Clinical, radiological, and pathological evaluation of \u201cNSIP with OP overlap\u201d pattern compared with NSIP in patients with idiopathic interstitial pneumonias","volume":"174","author":"Enomoto","year":"2020","journal-title":"Respir Med"},{"key":"2024102102542890000_60.4.2102411.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.05.002"},{"key":"2024102102542890000_60.4.2102411.23","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1002\/JLB.4RU0219-051RR","article-title":"Contribution of IDO to human respiratory syncytial virus infection","volume":"106","author":"Bonavente","year":"2019","journal-title":"J Leukoc Biol"},{"key":"2024102102542890000_60.4.2102411.24","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201304-0700OC"},{"key":"2024102102542890000_60.4.2102411.25","first-page":"101356","article-title":"Secondary organizing pneumonia after coronavirus disease 2019: two cases","volume":"32","author":"Kanaoka","year":"2021","journal-title":"Respir Med Case Rep"},{"key":"2024102102542890000_60.4.2102411.26","doi-asserted-by":"crossref","unstructured":"Bae I-G , Hong KW , Jang JW , et al. Persistent pneumonic consolidations due to secondary organizing pneumonia in a patient recovering from COVID-19 pneumonia: a case report. Research Square 2020; preprint [https:\/\/doi.org\/10.21203\/rs.3.rs-37580\/v1].","DOI":"10.21203\/rs.3.rs-37580\/v1"},{"key":"2024102102542890000_60.4.2102411.27","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.athoracsur.2021.06.076","article-title":"Pulmonary parenchymal changes in COVID-19 survivors","volume":"114","author":"Diaz","year":"2022","journal-title":"Ann Thorac Surg"},{"key":"2024102102542890000_60.4.2102411.28","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/his.14162","article-title":"COVID-19 related lung pathology: old patterns in new clothing?","volume":"77","author":"Nicholson","year":"2020","journal-title":"Histopathology"},{"key":"2024102102542890000_60.4.2102411.29","doi-asserted-by":"crossref","first-page":"310","DOI":"10.3892\/mmr.2017.6558","article-title":"Respiratory syncytial virus infection accelerates lung fibrosis through the unfolded protein response in a bleomycin-induced pulmonary fibrosis animal model","volume":"16","author":"Wang","year":"2017","journal-title":"Mol Med Rep"},{"key":"2024102102542890000_60.4.2102411.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2013.06.004"},{"key":"2024102102542890000_60.4.2102411.31","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/S0140-6736(21)01961-9","article-title":"Disease pathology in fibrotic interstitial lung disease: is it all about usual interstitial pneumonia?","volume":"398","author":"Renzoni","year":"2021","journal-title":"Lancet"},{"key":"2024102102542890000_60.4.2102411.32","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/modpathol.2016.147","article-title":"Epithelial to mesenchymal transition-related proteins ZEB1, \u03b2-catenin, and \u03b2-tubulin-III in idiopathic pulmonary fibrosis","volume":"30","author":"Chilosi","year":"2017","journal-title":"Mod Pathol"},{"key":"2024102102542890000_60.4.2102411.33","doi-asserted-by":"crossref","first-page":"e149336","DOI":"10.1172\/JCI149336","article-title":"Basal-epithelial stem cells cross an alarmin checkpoint for post-viral lung disease","volume":"131","author":"Wu","year":"2021","journal-title":"J Clin Invest"},{"key":"2024102102542890000_60.4.2102411.34","doi-asserted-by":"crossref","first-page":"4314","DOI":"10.1038\/s41467-021-24467-0","article-title":"Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity","volume":"12","author":"Bui","year":"2021","journal-title":"Nat Commun"},{"key":"2024102102542890000_60.4.2102411.35","doi-asserted-by":"publisher","DOI":"10.1172\/JCI141772"},{"key":"2024102102542890000_60.4.2102411.36","doi-asserted-by":"publisher","DOI":"10.1038\/nature13954"},{"key":"2024102102542890000_60.4.2102411.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2017.05.002"},{"key":"2024102102542890000_60.4.2102411.38","doi-asserted-by":"crossref","first-page":"673","DOI":"10.3389\/fimmu.2014.00673","article-title":"Cancer immunotherapy by targeting IDO1\/TDO and their downstream effectors","volume":"5","author":"Platten","year":"2015","journal-title":"Front Immunol"},{"key":"2024102102542890000_60.4.2102411.39","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e31823433ca"},{"key":"2024102102542890000_60.4.2102411.40","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2007.01942.x"},{"key":"2024102102542890000_60.4.2102411.41","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.3389\/fimmu.2018.03030","article-title":"Novel role for PD-1: PD-L1 as mediator of pulmonary vascular endothelial cell functions in pathogenesis of indirect ARDS in mice","volume":"9","author":"Lomas-Neira","year":"2018","journal-title":"Front Immunol"},{"key":"2024102102542890000_60.4.2102411.42","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.pulmoe.2020.10.010","article-title":"Reversibility of venous dilatation and parenchymal changes density in SARS-CoV-2 pneumonia: toward the definition of a peculiar pattern","volume":"27","author":"Piciucchi","year":"2021","journal-title":"Pulmonology"},{"key":"2024102102542890000_60.4.2102411.43","doi-asserted-by":"crossref","first-page":"e0033821","DOI":"10.1128\/spectrum.00338-21","article-title":"Amino acid metabolism is significantly altered at the time of admission in hospital for severe COVID-19 patients: findings from longitudinal targeted metabolomics analysis","volume":"9","author":"Ansone","year":"2021","journal-title":"Microbiol Spectr"},{"key":"2024102102542890000_60.4.2102411.44","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1002\/path.5842","article-title":"Indoleamine 2,3-dioxygenase (IDO)-1 and IDO-2 activity and severe course of COVID-19","volume":"256","author":"Guo","year":"2022","journal-title":"J Pathol"},{"key":"2024102102542890000_60.4.2102411.45","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.pulmoe.2021.03.003","article-title":"Pathophysiology of light phenotype SARS-CoV-2 interstitial pneumonia: from histopathological features to clinical presentations","volume":"28","author":"Oldani","year":"2022","journal-title":"Pulmonology"},{"key":"2024102102542890000_60.4.2102411.46","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3892\/ijo.2020.5159","article-title":"Immune-checkpoint inhibitors from cancer to COVID-19: a promising avenue for the treatment of patients with COVID-19 (Review)","volume":"58","author":"Vivarelli","year":"2021","journal-title":"Int J Oncol"},{"key":"2024102102542890000_60.4.2102411.47","doi-asserted-by":"crossref","first-page":"111957","DOI":"10.1016\/j.biopha.2021.111957","article-title":"Potential protective role of the anti-PD-1 blockade against SARS-CoV-2 infection","volume":"142","author":"Awadasseid","year":"2021","journal-title":"Biomed Pharmacother"},{"key":"2024102102542890000_60.4.2102411.48","doi-asserted-by":"crossref","first-page":"e146701","DOI":"10.1172\/jci.insight.146701","article-title":"PD-1 blockade counteracts post-COVID-19 immune abnormalities and stimulates the anti-SARS-CoV-2 immune response","volume":"6","author":"Loretelli","year":"2021","journal-title":"JCI Insight"},{"key":"2024102102542890000_60.4.2102411.49","doi-asserted-by":"crossref","unstructured":"Solomon JJ , Heyman B , Ko JP , et al. CT of postacute lung complications of COVID-19. Radiology 2021: E383\u2013E395. doi:10.1148\/radiol.2021211396","DOI":"10.1148\/radiol.2021211396"}],"container-title":["European Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/13993003.02411-2021","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T07:23:28Z","timestamp":1740381808000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/13993003.02411-2021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,17]]},"references-count":49,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,10,6]]},"published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1183\/13993003.02411-2021"],"URL":"https:\/\/doi.org\/10.1183\/13993003.02411-2021","relation":{},"ISSN":["0903-1936","1399-3003"],"issn-type":[{"value":"0903-1936","type":"print"},{"value":"1399-3003","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,17]]}}}