{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T01:32:00Z","timestamp":1793928720900,"version":"4.8.0"},"reference-count":48,"publisher":"European Respiratory Society (ERS)","issue":"3","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"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"}]},{"name":"COVID-19 Immunity Task Force"}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["ERJ Open Res"],"accepted":{"date-parts":[[2025,1,29]]},"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>It is unclear why patients with post-acute coronavirus disease 2019 sequelae (PACS) often present with persistent respiratory symptoms. We hypothesised that autoimmune inflammatory biomarkers may be associated with the persistence and\/or resolution of these symptoms. We performed symptom-based unsupervised cluster analysis to evaluate airway and systemic immune responses in PACS participants over time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Individuals with confirmed SARS-CoV-2 infection, a persistent range of PACS symptoms for &gt;12 weeks and no previous diagnosis of chronic lung disease were recruited and assessed at a 6-month follow-up. Assessments included St George's Respiratory Questionnaire (SGRQ), pulmonary function testing, 6-min walk test and analysis of blood and sputum inflammatory markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Unsupervised clustering based on SGRQ domains of 85 PACS individuals revealed four clusters. Cluster 1 (14%) reported no impairment and normal lung function, whereas clusters 2 (24%) and 3 (36%) were moderately symptomatic. Cluster 3 had a greater proportion of reduced lung function. Cluster 4 (26%) reported severe impairment across all SGRQ domains, with significantly lower 6-min walk distance, dyspnoea and fatigue. Clusters 3 and 4 had evidence of systemic inflammation (C-reactive protein and anti-SS-B\/La). Sputum analysis showed no evidence of airway inflammation in any cluster. After 6 months, improved symptoms in 43% of individuals correlated with increased forced expiratory volume in 1\u2005s percentage predicted and low serum interleukin-8 (p&lt;0.05) over time. Multivariate regression suggested that a reduction in serum anti-SS-B\/La IgG over 6 months was associated with improvement of SGRQ impact (t=3.17, p=0.003) and activity (t=2.04, p=0.005).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A subset of previously healthy PACS patients have clinically relevant respiratory burden as identified by unbiased SGRQ domain analysis associated with systemic inflammation and autoantibodies.<\/jats:p><\/jats:sec>","DOI":"10.1183\/23120541.01331-2024","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T12:08:41Z","timestamp":1741349321000},"page":"01331-2024","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Respiratory burden in post-acute COVID-19 sequelae: a longitudinal study of airway and systemic inflammation and clinical outcomes"],"prefix":"10.1183","volume":"11","author":[{"given":"Mei Nee","family":"Chiu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhiroop","family":"Chowdhury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snehal","family":"Somalwar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rameen","family":"Jamil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashutosh","family":"Thakar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Sidhom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nardien","family":"Sedhom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2683-5464","authenticated-orcid":false,"given":"Neel","family":"Thanavala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manan","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Kjarsgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen Garrido","family":"Venegas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisarg","family":"Radadia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia S.","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zil","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabila","family":"Ahammed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuma","family":"Isshiki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3995-7662","authenticated-orcid":false,"given":"Santi","family":"Nolasco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zain","family":"Chagla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3837-1467","authenticated-orcid":false,"given":"Martin","family":"Kolb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9197-2547","authenticated-orcid":false,"given":"Mylinh","family":"Duong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea S.","family":"Gershon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parameswaran","family":"Nair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4206-6000","authenticated-orcid":false,"given":"Imran","family":"Satia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Tselios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0412-6538","authenticated-orcid":false,"given":"Terence","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narayanaswamy","family":"Balakrishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Svenningsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7924-7211","authenticated-orcid":false,"given":"Manali","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"2025062304002686000_11.3.01331-2024.1","unstructured":"World Health Organisation (WHO) . Coronavirus disease (COVID-19): post COVID-19 condition. 2023. Date last accessed: 10 January 2024. www.who.int\/news-room\/questions-and-answers\/item\/coronavirus-disease-(covid-19)-post-covid-19-condition"},{"key":"2025062304002686000_11.3.01331-2024.2","unstructured":"Kuang S , Earl S , Clarke J , et al. Experiences of Canadians with long-term symptoms following COVID-19. Insights on Canadian Society, 2023."},{"key":"2025062304002686000_11.3.01331-2024.3","unstructured":"Johns Hopkins University of Medicine . COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). Date last accessed: 23 January 2024. https:\/\/coronavirus.jhu.edu\/map.html."},{"key":"2025062304002686000_11.3.01331-2024.4","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01947-2023"},{"key":"2025062304002686000_11.3.01331-2024.5","doi-asserted-by":"publisher","DOI":"10.1136\/bmjresp-2023-001770"},{"key":"2025062304002686000_11.3.01331-2024.6","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.7861\/clinmed.2020-0896","article-title":"Autonomic dysfunction in \u2018long COVID\u2019: rationale, physiology and management strategies","volume":"21","author":"Dani","year":"2021","journal-title":"Clin Med (Lond)"},{"key":"2025062304002686000_11.3.01331-2024.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2023.03.049"},{"key":"2025062304002686000_11.3.01331-2024.8","doi-asserted-by":"crossref","first-page":"e0290893","DOI":"10.1371\/journal.pone.0290893","article-title":"One-fourth of COVID-19 patients have an impaired pulmonary function after 12 months of disease onset. Yon DK, ed","volume":"18","author":"Van Willigen","year":"2023","journal-title":"PLoS ONE"},{"key":"2025062304002686000_11.3.01331-2024.9","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01532-2022"},{"key":"2025062304002686000_11.3.01331-2024.10","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s15010-021-01669-8","article-title":"Pulmonary function impairment of asymptomatic and persistently symptomatic patients 4 months after COVID-19 according to disease severity","volume":"50","author":"Munker","year":"2022","journal-title":"Infection"},{"key":"2025062304002686000_11.3.01331-2024.11","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiac017"},{"key":"2025062304002686000_11.3.01331-2024.12","doi-asserted-by":"crossref","first-page":"2200970","DOI":"10.1183\/13993003.00970-2022","article-title":"Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long-COVID symptoms","volume":"61","author":"Son","year":"2022","journal-title":"Eur Respir J"},{"key":"2025062304002686000_11.3.01331-2024.13","unstructured":"World Health Organization . A clinical case definition of post-COVID-19 condition by a Delphi consensus. Date last accessed: 11 March 2023. www.who.int\/publications\/i\/item\/WHO-2019-nCoV-Post_COVID-19_condition-Clinical_case_definition-2021.1"},{"key":"2025062304002686000_11.3.01331-2024.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2011.05.004"},{"key":"2025062304002686000_11.3.01331-2024.15","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02089-2015"},{"key":"2025062304002686000_11.3.01331-2024.16","doi-asserted-by":"publisher","DOI":"10.1136\/thorax.58.4.339"},{"key":"2025062304002686000_11.3.01331-2024.17","doi-asserted-by":"publisher","DOI":"10.1136\/bmjresp-2021-001136"},{"key":"2025062304002686000_11.3.01331-2024.18","doi-asserted-by":"publisher","DOI":"10.1081\/COPD-200050513"},{"key":"2025062304002686000_11.3.01331-2024.19","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00102509"},{"key":"2025062304002686000_11.3.01331-2024.20","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.96.09061174"},{"key":"2025062304002686000_11.3.01331-2024.21","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.jaci.2017.06.033","article-title":"Sputum autoantibodies in patients with severe eosinophilic asthma","volume":"141","author":"Mukherjee","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"2025062304002686000_11.3.01331-2024.22","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00016-2016"},{"key":"2025062304002686000_11.3.01331-2024.23","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201908-1590ST"},{"key":"2025062304002686000_11.3.01331-2024.24","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00150314"},{"key":"2025062304002686000_11.3.01331-2024.25","unstructured":"R Core Team . R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria . 2021. www.R-project.org\/"},{"key":"2025062304002686000_11.3.01331-2024.26","unstructured":"Meyer D , Dimitriadou E , Hornik K , et al. E1071: misc functions of the department of statistics, TU Wien. R package version 17\u201311. 2022. https:\/\/CRAN.R-project.org\/package=e1071"},{"key":"2025062304002686000_11.3.01331-2024.27","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.161.2.9903097"},{"key":"2025062304002686000_11.3.01331-2024.28","doi-asserted-by":"crossref","first-page":"7717","DOI":"10.1038\/s41598-023-34678-8","article-title":"Impaired health-related quality of life in long-COVID syndrome after mild to moderate COVID-19","volume":"13","author":"Malesevic","year":"2023","journal-title":"Sci Rep"},{"key":"2025062304002686000_11.3.01331-2024.29","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.18931"},{"key":"2025062304002686000_11.3.01331-2024.30","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02411-2021"},{"key":"2025062304002686000_11.3.01331-2024.31","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.212170"},{"key":"2025062304002686000_11.3.01331-2024.32","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13558"},{"key":"2025062304002686000_11.3.01331-2024.33","doi-asserted-by":"crossref","first-page":"e222888","DOI":"10.1148\/radiol.222888","article-title":"Longitudinal assessment of chest CT findings and pulmonary function after COVID-19 infection","volume":"307","author":"Han","year":"2023","journal-title":"Radiology"},{"key":"2025062304002686000_11.3.01331-2024.34","doi-asserted-by":"crossref","first-page":"e222462","DOI":"10.1148\/radiol.222462","article-title":"Current and emerging knowledge in COVID-19","volume":"306","author":"Jeong","year":"2023","journal-title":"Radiology"},{"key":"2025062304002686000_11.3.01331-2024.35","doi-asserted-by":"publisher","DOI":"10.1136\/thorax-2022-219378"},{"key":"2025062304002686000_11.3.01331-2024.36","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1002\/jmri.28940","article-title":"Review of hyperpolarized pulmonary functional129 Xe MR for long-COVID","volume":"59","author":"Wild","year":"2024","journal-title":"Magn Reson Imaging"},{"key":"2025062304002686000_11.3.01331-2024.37","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S2213-2600(23)00239-4","article-title":"Post-acute sequelae of COVID-19: understanding and addressing the burden of multisystem manifestations","volume":"11","author":"Parotto","year":"2023","journal-title":"Lancet Respir Med"},{"key":"2025062304002686000_11.3.01331-2024.38","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00089-2020"},{"key":"2025062304002686000_11.3.01331-2024.39","doi-asserted-by":"crossref","first-page":"e14415","DOI":"10.14814\/phy2.14415","article-title":"The contribution of FEV 1 and airflow limitation on the intensity of dyspnea and leg effort during exercise. Insights from a real-world cohort","volume":"8","author":"Satia","year":"2020","journal-title":"Physiol Rep"},{"key":"2025062304002686000_11.3.01331-2024.40","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3389\/fpsyt.2020.00107","article-title":"The Role of chronic stress in normal visceroception: insights from an experimental visceral pain study in healthy volunteers","volume":"11","author":"Icenhour","year":"2020","journal-title":"Front Psychiatry"},{"key":"2025062304002686000_11.3.01331-2024.41","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.immuni.2022.01.017","article-title":"Immuno-proteomic profiling reveals aberrant immune cell regulation in the airways of individuals with ongoing post-COVID-19 respiratory disease","volume":"55","author":"Vijayakumar","year":"2022","journal-title":"Immunity"},{"key":"2025062304002686000_11.3.01331-2024.42","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abo5795"},{"key":"2025062304002686000_11.3.01331-2024.43","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0011-2016"},{"key":"2025062304002686000_11.3.01331-2024.44","doi-asserted-by":"crossref","first-page":"103071","DOI":"10.1016\/j.autneu.2022.103071","article-title":"Investigating the possible mechanisms of autonomic dysfunction post-COVID-19","volume":"245","author":"Jammoul","year":"2023","journal-title":"Auton Neurosci"},{"key":"2025062304002686000_11.3.01331-2024.45","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.3390\/v13112239","article-title":"Lasting changes to circulating leukocytes in people with mild SARS-CoV-2 infections","volume":"13","author":"Kennedy","year":"2021","journal-title":"Viruses"},{"key":"2025062304002686000_11.3.01331-2024.46","doi-asserted-by":"crossref","unstructured":"Chen H-J , Appelman B , Willemen H , et al. Transfer of IgG from long COVID patients induces symptomology in mice. bioRxiv 2024; preprint doi:10.1101\/2024.05.30.596590","DOI":"10.1101\/2024.05.30.596590"},{"key":"2025062304002686000_11.3.01331-2024.47","doi-asserted-by":"crossref","unstructured":"Santos Guedes De Sa K , Silva J , Bayarri-Olmos R , et al. A causal link between autoantibodies and neurological symptoms in long COVID. medRxiv 2024 ; preprint [https:\/\/doi.org\/10.1101\/2024.06.18.24309100].","DOI":"10.1101\/2024.06.18.24309100"},{"key":"2025062304002686000_11.3.01331-2024.48","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1001\/jama.2020.17709","article-title":"As Their numbers grow, COVID-19 \u201clong haulers\u201d stump experts","volume":"324","author":"Rubin","year":"2020","journal-title":"JAMA"}],"container-title":["ERJ Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/23120541.01331-2024","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T11:00:38Z","timestamp":1750676438000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/23120541.01331-2024"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,27]]},"references-count":48,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,6,23]]},"published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1183\/23120541.01331-2024"],"URL":"https:\/\/doi.org\/10.1183\/23120541.01331-2024","relation":{},"ISSN":["2312-0541"],"issn-type":[{"value":"2312-0541","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,27]]}}}