{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:56:46Z","timestamp":1790607406153,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Pulmonary function impairment significantly affects quality of life, work ability, and healthcare utilization. Among patients with COVID-19, respiratory symptoms vary in severity. This study aimed to assess whether biomarkers related to respiratory function and inflammation at emergency department (ED) admittance can predict long-term pulmonary function impairment in COVID-19 survivors. Methods: This prospective single-center study recruited patients 4\u20135 months post-COVID-19 infection using consecutive sampling. All attendees at the respiratory outpatient clinic were invited to participate. Pulmonary function tests, including diffusing capacity of the lungs for carbon monoxide (DLCO), total lung capacity (TLC), forced expiratory volume in the first second (FEV1), and forced vital capacity (FVC), were performed, with DLCO &lt; 80% as the key indicator of impairment. Baseline biomarkers\u2014C-Reactive Protein (CRP), leukocyte counts, and soluble urokinase Plasminogen Activator Receptor (suPAR)\u2014were correlated with post-discharge DLCO values. Results: This study enrolled 110 patients with COVID-19; 58.2% were female, the median age was 61.5, and the average BMI was 27.2. Smoking history showed that 53.7% were never smokers, 43.5% were former smokers, and 2.8% were current smokers. A diffusion deficit (DLCO &lt; 80%) was present in 48.6% of patients. Leukocyte counts and suPAR had the highest sensitivity (&gt;0.80) for predicting DLCO impairment but showed low specificity and a positive predictive value (PPV) of around 0.50. However, combining all biomarkers improved prediction accuracy, with a negative predictive value (NPV) of 0.93. Conclusions: The chosen inflammatory biomarkers by themselves had a limited ability to predict long-term pulmonary function impairment in COVID-19 survivors. However, when combined, they demonstrated a high negative predictive value (NPV) for identifying DLCO impairment. This strategy could help clinicians better tailor follow-up care for patients with COVID-19.<\/jats:p>","DOI":"10.3390\/jcm14051717","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T04:58:17Z","timestamp":1741064297000},"page":"1717","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Predictive Role of C-Reactive Protein, Leukocyte Cell Count, and Soluble Urokinase Plasminogen Activator Receptor for Pulmonary Sequelae in Hospitalized COVID-19 Survivors: A Prospective Single-Center Cohort Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Izzet","family":"Altintas","sequence":"first","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"},{"name":"Emergency Department, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7356-6481","authenticated-orcid":false,"given":"Thomas","family":"Kallemose","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3892-6645","authenticated-orcid":false,"given":"Mette Bendtz","family":"Lindstr\u00f8m","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran","family":"Parvaiz","sequence":"additional","affiliation":[{"name":"Emergency Department, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iben","family":"Rokkedal","sequence":"additional","affiliation":[{"name":"Emergency Department, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6864-963X","authenticated-orcid":false,"given":"Lene Juel","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrine Kj\u00e6r","family":"Iversen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4630-4275","authenticated-orcid":false,"given":"Jesper","family":"Eugen-Olsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"},{"name":"Emergency Department, Copenhagen University Hospital Herlev and Gentofte, 2730 Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasper Karmark","family":"Iversen","sequence":"additional","affiliation":[{"name":"Emergency Department, Copenhagen University Hospital Herlev and Gentofte, 2730 Herlev, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7269-0712","authenticated-orcid":false,"given":"Ejvind Frausing","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8689-3695","authenticated-orcid":false,"given":"Charlotte Suppli","family":"Ulrik","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, University of Copenhagen, 2100 Copenhagen, Denmark"},{"name":"Department of Respiratory Medicine, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Olof","family":"Nehlin","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ove","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"},{"name":"Emergency Department, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tudoran, C., Tudoran, M., Lazureanu, V.E., Marinescu, A.R., Cut, T.G., Oancea, C., Pescariu, S.A., and Pop, G.N. (2021). Factors Influencing the Evolution of Pulmonary Hypertension in Previously Healthy Subjects Recovering from a SARS-CoV-2 Infection. J. Clin. Med., 10.","DOI":"10.37247\/PAMED4ED.4.22.4"},{"key":"ref_2","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":"ref_3","doi-asserted-by":"crossref","first-page":"101019","DOI":"10.1016\/j.eclinm.2021.101019","article-title":"Characterizing long COVID in an international cohort: 7 months of symptoms and their impact","volume":"38","author":"Davis","year":"2021","journal-title":"eClinicalMedicine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2024735","DOI":"10.1080\/20018525.2021.2024735","article-title":"Hospital admission for COVID-19 pneumonitis\u2014Long-term impairment in quality of life and lung function","volume":"9","author":"Vejen","year":"2022","journal-title":"Eur. Clin. Respir. J."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Benedetto, I.G., da Silva, R.M.C., Hetzel, G.M., da Silva Viana, G., Guimar\u00e3es, A.R., Folador, L., Brentano, V.B., Garcia, T.S., Ribeiro, S.P., and de Tarso Roth Dalcin, P. (2023). Impact of impaired pulmonary function on clinical outcomes in survivors of severe COVID-19 without pre-existing respiratory disease. J. Bras. Pneumol., e20220452.","DOI":"10.36416\/1806-3756\/e20220452"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.cmi.2021.02.019","article-title":"Pulmonary long-term consequences of COVID-19 infections after hospital discharge","volume":"27","author":"Blanco","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"eabj7790","DOI":"10.1126\/scitranslmed.abj7790","article-title":"Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19","volume":"13","author":"Walters","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_8","first-page":"CD013879","article-title":"COVID-19 and its cardiovascular effects: A systematic review of prevalence studies","volume":"2022","author":"Pellicori","year":"2021","journal-title":"Cochrane Database Syst. Rev. [Internet]"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/MCC.0000000000000911","article-title":"Pathophysiology of coronavirus-19 disease acute lung injury","volume":"28","author":"Camporota","year":"2022","journal-title":"Curr. Opin. Crit. Care"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"The Lille COVID-19 ICU and Anatomopathology Group, Copin, M.C., Parmentier, E., Duburcq, T., Poissy, J., and Mathieu, D. (2020). Time to consider histologic pattern of lung injury to treat critically ill patients with COVID-19 infection. Intensive Care Med., 46, 1124\u20131126.","DOI":"10.1007\/s00134-020-06057-8"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2001217","DOI":"10.1183\/13993003.01217-2020","article-title":"Abnormal pulmonary function in Patients with COVID-19 at time of hospital discharge","volume":"55","author":"Mo","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e001347","DOI":"10.1136\/bmjresp-2022-001347","article-title":"Respiratory function and CT abnormalities among survivors of COVID-19 pneumonia: A nationwide follow-up study","volume":"9","author":"Axelsson","year":"2022","journal-title":"BMJ Open Respir. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"109676","DOI":"10.1016\/j.ejrad.2021.109676","article-title":"Post-discharge chest CT findings and pulmonary function tests in severe Patients with COVID-19","volume":"138","author":"Balbi","year":"2021","journal-title":"Eur. J. Radiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1136\/thorax-2022-219378","article-title":"Longitudinal follow-up of postacute COVID-19 syndrome: DLCO, quality-of-life and MRI pulmonary gas-exchange abnormalities","volume":"78","author":"Matheson","year":"2023","journal-title":"Thorax"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Altintas, I., Eugen-Olsen, J., Sepp\u00e4l\u00e4, S., Tingleff, J., Stauning, M.A., El Caidi, N.O., Elmajdoubi, S., Gamst-Jensen, H., Lindstr\u00f8m, M.B., and Rasmussen, L.J.H. (2021). suPAR Cut-Offs for Risk Stratification in Patients With Symptoms of COVID-19. Biomark. Insights, 16.","DOI":"10.1177\/11772719211034685"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Littlefield, K.M., Watson, R.O., Schneider, J.M., Neff, C.P., Yamada, E., Zhang, M., Campbell, T.B., Falta, M.T., Jolley, S.E., and Fontenot, A.P. (2022). SARS-CoV-2-specific T cells associate with inflammation and reduced lung function in pulmonary post-acute sequalae of SARS-CoV-2. PLOS Pathog., 18.","DOI":"10.1101\/2022.02.14.480317"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.immuni.2021.03.005","article-title":"Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19","volume":"54","author":"Szabo","year":"2021","journal-title":"Immunity"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mancilla-Ceballos, R., Milne, K.M., Guenette, J.A., and Cortes-Telles, A. (2023). Inflammation associated with lung function abnormalities in COVID-19 survivors. BMC Pulm. Med., 23.","DOI":"10.1186\/s12890-023-02521-5"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1600016","DOI":"10.1183\/13993003.00016-2016","article-title":"2017 ERS\/ATS standards for single-breath carbon monoxide uptake in the lung","volume":"49","author":"Graham","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e70","DOI":"10.1164\/rccm.201908-1590ST","article-title":"Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement","volume":"200","author":"Graham","year":"2019","journal-title":"Am. J. Respir. Crit Care Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1183\/09041950.005s1693","article-title":"Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society","volume":"16","author":"Quanjer","year":"1993","journal-title":"Eur. Respir. J. Suppl."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1183\/09041950.041s1693","article-title":"Standardization of the measurement of transfer factor (diffusing capacity). Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society","volume":"16","author":"Cotes","year":"1993","journal-title":"Eur. Respir. J. Suppl."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.jemermed.2021.03.012","article-title":"Soluble Urokinase Plasminogen Activator Receptor as a Decision Marker for Early Discharge of Patients with COVID-19 Symptoms in the Emergency Department","volume":"61","author":"Stauning","year":"2021","journal-title":"J. Emerg. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1007\/s15010-021-01638-1","article-title":"COVID-19: Persistence of symptoms and lung alterations after 3\u20136 months from hospital discharge","volume":"49","author":"Fortini","year":"2021","journal-title":"Infection"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Reynolds, H.Y. (2012). Respiratory Structure and Function. Goldman\u2019s Cecil Medicine [Internet], Elsevier. Available online: https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/B9781437716047000853.","DOI":"10.1016\/B978-1-4377-1604-7.00553-4"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1378\/chest.110.6.1430","article-title":"Membrane Diffusion and Capillary Blood Volume in Chronic Thromboembolic Pulmonary Hypertension","volume":"110","author":"Bernstein","year":"1996","journal-title":"Chest"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s12024-020-00310-8","article-title":"Autopsy findings in COVID-19-related deaths: A literature review","volume":"17","author":"Maiese","year":"2021","journal-title":"Forensic Sci. Med. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e069590","DOI":"10.1136\/bmj-2021-069590","article-title":"Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: Nationwide self-controlled cases series and matched cohort study","volume":"377","author":"Katsoularis","year":"2022","journal-title":"BMJ"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1186\/s12931-019-1234-4","article-title":"The biomarkers suPAR and blood eosinophils are associated with hospital readmissions and mortality in asthma\u2014A retrospective cohort study","volume":"20","author":"Hakansson","year":"2019","journal-title":"Respir. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"733","DOI":"10.2147\/COPD.S229904","article-title":"High suPAR and Low Blood Eosinophil Count are Risk Factors for Hospital Readmission and Mortality in Patients with COPD","volume":"15","author":"Ulrik","year":"2020","journal-title":"Int. J. Chron. Obstruct. Pulm\u00f3n. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Notarte, K.I., de Oliveira, M.H.S., Peligro, P.J., Velasco, J.V., Macaranas, I., Ver, A.T., Pangilinan, F.C., Pastrana, A., Goldrich, N., and Kavteladze, D. (2022). Age, Sex and Previous Comorbidities as Risk Factors Not Associated with SARS-CoV-2 Infection for Long COVID-19: A Systematic Review and Meta-Analysis. J. Clin. Med., 11.","DOI":"10.3390\/jcm11247314"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1038\/s41591-021-01499-z","article-title":"Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: A double-blind, randomized controlled phase 3 trial","volume":"27","author":"Kyriazopoulou","year":"2021","journal-title":"Nat. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"106394","DOI":"10.1016\/j.rmed.2021.106394","article-title":"Impaired diffusing capacity for carbon monoxide is common in critically ill Patients with COVID-19 at four months post-discharge","volume":"182","author":"Ekbom","year":"2021","journal-title":"Respir. Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/5\/1717\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:46:44Z","timestamp":1760028404000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/5\/1717"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,4]]},"references-count":33,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["jcm14051717"],"URL":"https:\/\/doi.org\/10.3390\/jcm14051717","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,4]]}}}