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In this longitudinal cohort study of individuals followed up at 4 (n = 57) and 7 months (n = 54) after the Omicron BA.5 outbreak in China, we comprehensively analyzed physician-administered PASC symptom assessments, clinical respiratory evaluations (pulmonary function and chest computed tomography), immunological response profiles, and inflammatory markers. Our findings demonstrated that patients with respiratory system\u2013specific PASC (R-PASC) endure long-term pulmonary function impairment (restrictive ventilation and diffusion dysfunction), sustained severe residual lung lesions (predominant fibrosis), and chronic systemic inflammatory responses. Patients with R-PASC exhibited enhanced SARS-CoV-2\u2013specific T-cell responses, whereas in the control group, moderate-magnitude and polyfunctional virus-specific T-cell response correlated with improved lung function and alleviated inflammation. Sustained neutralizing antibody titers were also observed in patients with R-PASC, whereas humoral responses showed minimal association with disease pathophysiology. Moreover, prolonged activation of complement classical and alternative pathway in patients with R-PASC is associated with worsening respiratory parameters, whereas mannose-binding lectin within the lectin pathway exhibits protective correlations with pulmonary tissue function preservation. Overall, our study delineates the extensively perturbed immune\u2013inflammation\u2013organ dysfunction in patients with R-PASC, thereby providing valuable insights into the pathogenesis of this condition and highlighting potential targets for therapeutic intervention.<\/jats:p>","DOI":"10.1093\/ofid\/ofag050","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T12:41:39Z","timestamp":1770122499000},"source":"Crossref","is-referenced-by-count":0,"title":["Extensive Immunological and Inflammatory Perturbation Underpins the Respiratory Sequelae of Postacute COVID-19"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5063-0338","authenticated-orcid":false,"given":"Gang","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University , Guangzhou ,","place":["China"]},{"name":"Guangzhou National Laboratory, Bioland , Guangzhou, Guangdong ,","place":["China"]},{"name":"The Affiliated Hospital of Kunming University of Science and Technology. Department of Respiratory and Critical Care Medicine, The First People's Hospital of Yunnan Province , Kunming, Yunnan ,","place":["China"]},{"name":"Yunnan Baiyao Group Co., Ltd., Central Research Institute , Kunming, Yunnan ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinpeng","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University , Guangzhou ,","place":["China"]},{"name":"Guangzhou National Laboratory, Bioland , Guangzhou, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shidong","family":"Deng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University , Guangzhou ,","place":["China"]},{"name":"Guangzhou National Laboratory, Bioland , Guangzhou, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingjiao","family":"Xia","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Kunming University of Science and Technology. Department of Respiratory and Critical Care Medicine, The First People's Hospital of Yunnan Province , Kunming, Yunnan ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Kunming University of Science and Technology. Department of Respiratory and Critical Care Medicine, The First People's Hospital of Yunnan Province , Kunming, Yunnan ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Qin","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Kunming University of Science and Technology. Department of Respiratory and Critical Care Medicine, The First People's Hospital of Yunnan Province , Kunming, Yunnan ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyun","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University , Guangzhou ,","place":["China"]},{"name":"Guangzhou National Laboratory, Bioland , Guangzhou, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Sun","sequence":"additional","affiliation":[{"name":"Yunnan Baiyao Group Co., Ltd., Central Research Institute , Kunming, Yunnan ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daxiang","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University , Guangzhou ,","place":["China"]},{"name":"Guangzhou National Laboratory, Bioland , Guangzhou, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Sun","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Kunming University of Science and Technology. 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