{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:49:51Z","timestamp":1790729391751,"version":"4.1.0"},"reference-count":40,"publisher":"European Respiratory Society (ERS)","issue":"3","license":[{"start":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:00:00Z","timestamp":1707350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016652","name":"Duke Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016652","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2024,1,26]]},"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Long COVID impacts \u223c10% of people diagnosed with coronavirus disease 2019 (COVID-19), yet the pathophysiology driving ongoing symptoms is poorly understood. We hypothesised that<jats:sup>129<\/jats:sup>Xe magnetic resonance imaging (MRI) could identify unique pulmonary phenotypic subgroups of long COVID. Therefore, we evaluated ventilation and gas exchange measurements with cluster analysis to generate imaging-based phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>COVID-negative controls and participants who previously tested positive for COVID-19 underwent<jats:sup>129<\/jats:sup>Xe MRI \u223c14\u2005months post-acute infection across three centres. Long COVID was defined as persistent dyspnoea, chest tightness, cough, fatigue, nausea and\/or loss of taste\/smell at MRI; participants reporting no symptoms were considered fully recovered.<jats:sup>129<\/jats:sup>Xe MRI ventilation defect percent (VDP) and membrane-to-gas (Mem\/Gas), red blood cell-to-membrane (RBC\/Mem) and red blood cell-to-gas (RBC\/Gas) ratios were used in k-means clustering for long COVID, and measurements were compared using ANOVA with post-hoc Bonferroni correction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We evaluated 135 participants across three centres: 28 COVID-negative (mean\u00b1<jats:sc>sd<\/jats:sc>age 40\u00b116\u2005years), 34 fully recovered (42\u00b114\u2005years) and 73 long COVID (49\u00b113\u2005years). RBC\/Mem (p=0.03) and forced expiratory volume in 1\u2005s (FEV<jats:sub>1<\/jats:sub>) (p=0.04) were different between long COVID and COVID-negative; FEV<jats:sub>1<\/jats:sub>and all other pulmonary function tests (PFTs) were within normal ranges. Four unique long COVID clusters were identified compared with recovered and COVID-negative. Cluster 1 was the youngest with normal MRI and mild gas trapping; Cluster 2 was the oldest, characterised by reduced RBC\/Mem but normal PFTs; Cluster 3 had mildly increased Mem\/Gas with normal PFTs; and Cluster 4 had markedly increased Mem\/Gas with concomitant reduction in RBC\/Mem and restrictive PFT pattern.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified four<jats:sup>129<\/jats:sup>Xe MRI long COVID phenotypes with distinct characteristics.<jats:sup>129<\/jats:sup>Xe MRI can dissect pathophysiological heterogeneity of long COVID to enable personalised patient care.<\/jats:p><\/jats:sec>","DOI":"10.1183\/13993003.02301-2023","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T16:45:23Z","timestamp":1707410723000},"page":"2302301","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Cluster analysis to identify long COVID phenotypes using<sup>129<\/sup>Xe magnetic resonance imaging: a multicentre evaluation"],"prefix":"10.1183","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2541-1645","authenticated-orcid":false,"given":"Rachel L.","family":"Eddy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Mummy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aryil","family":"Bechtel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradie","family":"Frizzell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firoozeh V.","family":"Gerayeli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathon A.","family":"Leipsic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice M.","family":"Leung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastiaan","family":"Driehuys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9188-9244","authenticated-orcid":false,"given":"Loretta G.","family":"Que","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don D.","family":"Sin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Niedbalski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2024,2,8]]},"reference":[{"key":"2024102103225481000_63.3.2302301.1","unstructured":"National Institute for Health and Care Excellence . COVID-19 rapid guideline: managing the long-term effects of COVID-19. 2020. www.nice.org.uk\/guidance\/ng188 Date last accessed: 2 February 2024."},{"key":"2024102103225481000_63.3.2302301.2","unstructured":"US Centers for Disease Control and Prevention . Long COVID or post-COVID conditions. 2023. www.cdc.gov\/coronavirus\/2019-ncov\/long-term-effects\/index.html Date last accessed: 4 September 2023."},{"key":"2024102103225481000_63.3.2302301.3","unstructured":"World Health Organisation . A clinical case definition of post COVID-19 condition by a Delphi consensus. 2021. www.who.int\/publications\/i\/item\/WHO-2019-nCoV-Post_COVID-19_condition-Clinical_case_definition-2021.1 Date last accessed: 2 February 2024."},{"key":"2024102103225481000_63.3.2302301.4","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.18931"},{"key":"2024102103225481000_63.3.2302301.5","doi-asserted-by":"publisher","DOI":"10.1093\/INFDIS\/JIAC136"},{"key":"2024102103225481000_63.3.2302301.6","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41579-022-00846-2","article-title":"Long COVID: major findings, mechanisms and recommendations","volume":"21","author":"Davis","year":"2023","journal-title":"Nat Rev Microbiol"},{"key":"2024102103225481000_63.3.2302301.7","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7232a3"},{"key":"2024102103225481000_63.3.2302301.8","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1038\/s41591-023-02521-2","article-title":"Postacute 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