{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:11:19Z","timestamp":1779192679010,"version":"3.51.4"},"reference-count":48,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study evaluated the diagnostic usefulness of surfactant protein D (SP-D), chemokine C-C motif ligand 2\/monocyte chemoattractant protein-1 (CCL2\/MCP-1), and interleukin 18 (IL-18) in patients with SARS-CoV-2 infection. The authors focused on lung failure assessment, lung parenchyma involvement, and the early assessment of the risk of developing pulmonary fibrosis at the onset of COVID-19. The study group included 87 patients with COVID-19 and 45 healthy subjects. Concentrations of all three markers were measured using the enzyme immunoassay method. The serum SP-D, CCL2\/MCP-1, and IL-18 concentrations were significantly higher in the COVID-19 patients before admission to the hospital than those in the controls (p &lt; 0.001 for all comparisons). Differences were only found in the IL-18 levels between the groups categorized according to disease severity (p &lt; 0.001); levels were significantly higher in patients with critical disease severity compared to those with moderate disease severity (p &lt; 0.001). IL-18 also showed a positive correlation with the disease severity (p = 0.025). SP-D and IL-18 levels varied depending on the amount of oxygen administration (p = 0.017 and p &lt; 0.001, respectively). Among the blood gas parameters, SP-D levels were negatively associated with the partial pressure of arterial oxygen (PaO2) and oxygen saturation (O2Sat) (p = 0.026 and p = 0.048, respectively), IL-18 with O2Sat (p = 0.036), and CCL2\/MCP-1 with PaO2 (p = 0.042). SP-D and IL-18 were significantly negatively correlated with oxygen therapy (p = 0.003 and p = 0.014, respectively). Conversely, CCL2\/MCP-1 was significantly positively correlated with the pulmonary involvement severity (p = 0.017) and level of hyaluronic acid (HA), a marker of fibrosis (p = 0.042). We also observed a significant correlation between the IL-18 level and the pulmonary involvement severity (p &lt; 0.001), HA (p &lt; 0.001), and other markers of fibrosis. In summary, our study\u2019s results indicate that SP-D, CCL2\/MCP-1, and IL-18 may be used to assess lung function in the early stage of COVID-19 infection; additionally, SP-D may serve as an indicator of alveolar injury, while CCL2\/MCP-1 and IL-18 may be markers of lung parenchyma involvement and potential predictors of the development of pulmonary fibrosis.<\/jats:p>","DOI":"10.3390\/ijms27104190","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T19:10:52Z","timestamp":1778267452000},"page":"4190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic Usefulness of SP-D, CCL2\/MCP-1, and IL-18 in Assessing Respiratory Function and Risk of Pulmonary Fibrosis in COVID-19 Patients"],"prefix":"10.3390","volume":"27","author":[{"given":"Bogdan","family":"Cylwik","sequence":"first","affiliation":[{"name":"Department of Paediatric Laboratory Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kacper","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Internal Diseases, Voivodeship Hospital in Bialystok, 15-278 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2013-3023","authenticated-orcid":false,"given":"Marcin","family":"Kazberuk","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Internal Diseases, Voivodeship Hospital in Bialystok, 15-278 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7702-5148","authenticated-orcid":false,"given":"Ewa","family":"Gruszewska","sequence":"additional","affiliation":[{"name":"Department of Biochemical Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anatol","family":"Panasiuk","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Internal Diseases, Voivodeship Hospital in Bialystok, 15-278 Bialystok, Poland"},{"name":"Department of Clinical Medicine, Medical University of Bialystok, 15-269 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Sienkiewicz","sequence":"additional","affiliation":[{"name":"Department of Paediatric Laboratory Diagnostics, Medical University of Bialystok Children\u2019s Clinical Hospital, 15-274 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malgorzata","family":"Wojtkowska","sequence":"additional","affiliation":[{"name":"Department of Paediatric Laboratory Diagnostics, Medical University of Bialystok Children\u2019s Clinical Hospital, 15-274 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6701-1861","authenticated-orcid":false,"given":"Lech","family":"Chrostek","sequence":"additional","affiliation":[{"name":"Department of Biochemical Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Severe features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1055\/s-0040-1712187","article-title":"Epidemiology of COVID-19","volume":"11","author":"Chowdhury","year":"2020","journal-title":"J. Dig. Endosc."},{"key":"ref_3","unstructured":"(2024). WHO COVID-19 Dashboard, World Health Organization. Available online: https:\/\/covid19.who.int\/."},{"key":"ref_4","first-page":"1861","article-title":"Clinical characteristics of COVID-19 in China","volume":"382","author":"Guan","year":"2020","journal-title":"Reply. N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/nrd.2017.170","article-title":"Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease","volume":"16","author":"Mora","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"173","DOI":"10.4103\/atm.atm_7_23","article-title":"Post-COVID-19 pulmonary fibrosis: An ongoing concern","volume":"18","author":"Aljarhi","year":"2023","journal-title":"Ann. Thorac. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.arbres.2022.03.007","article-title":"Pulmonary fibrosis in the time of COVID-19","volume":"58","author":"Buendia","year":"2022","journal-title":"Arch. Bronconeumol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lassan, S., Tesar, T., Tisonova, J., and Lassanova, M. (2023). Pharmacological approaches to pulmonary fibrosis following COVID-19. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1143158"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e70034","DOI":"10.1002\/ctd2.70034","article-title":"Post-COVID-19 pulmonary fibrosis: Mechanisms, biomarkers, and therapeutic perspectives","volume":"5","author":"Sardarni","year":"2025","journal-title":"Clin. Transl. Disc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2101499","DOI":"10.1183\/13993003.01499-2021","article-title":"ERS\/ATS technical standard on interpretive strategies for routine lung function tests","volume":"60","author":"Stanojevic","year":"2022","journal-title":"Eur. Respir. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1515\/cclm-2021-0199","article-title":"Prognostic role of Krebs von den Lungen-6 (KL-6) measurement in idiopathic pulmonary fibrosis: A systematic review and meta-analysis","volume":"59","author":"Ioisio","year":"2021","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.clinbiochem.2023.01.010","article-title":"Krebs von den Lungen-6 (KL-6) as a diagnostic marker for pulmonary fibrosis: A systematic review and meta-analysis","volume":"114","author":"Wang","year":"2023","journal-title":"Clin. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1111\/jcmm.16275","article-title":"Identification of key candidate biomarkers for severe influenza infection by integrated bioinformatical analysis and initial clinical validation","volume":"25","author":"Liu","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Da-Silva-Neto, P.V., Do Valle, V.B., Fuzo, C.A., Fernandes, T.M., Toro, D.M., Fraga-Silva, T.F.C., Basile, P.A., de Carvalho, J.C.S., Pimentel, V.E., and Perez, M.M. (2022). Matrix metalloproteinases on severe COVID-19 lung disease pathogenesis: Cooperative actions of MMP-8\/MMP-2 axis on immune response through HLA-G shedding and oxidative stress. Biomolecules, 12.","DOI":"10.3390\/biom12050604"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"108","DOI":"10.55133\/eji.310411","article-title":"Impact of serum IL-10 level on the clinical outcome of COVID-19 patients and the development of post-COVID pulmonary fibrosis","volume":"31","author":"Mariam","year":"2024","journal-title":"Egypt J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hrenak, J., and Simko, F. (2020). Renin-angiotensin system: An important player in the pathogenesis of acute respiratory distress syndrome. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218038"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Pan, X., Huang, Z., Tao, N., Huang, C., Wang, S., Cheng, Z., Fan, R., and Liu, S. (2025). Increase circulating levels of SP-D and IL-10 are associated with the development of disease severity and pulmonary fibrosis in patients with COVID-19. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1553283"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"107598","DOI":"10.1016\/j.intimp.2021.107598","article-title":"MCP-1: Function, regulation, and involvement in disease","volume":"101","author":"Singh","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yasuda, K., Nakanishi, K., and Tsutsui, H. (2019). Interleukin-18 in health and disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030649"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.1017\/S0950268821002636","article-title":"Interleukin-18 and COVID-19","volume":"150","author":"Schooling","year":"2021","journal-title":"Epidemiol. Infect."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40635-022-00488-x","article-title":"Elevated free interleukin-18 associated with severity and mortality in prospective cohort study of 206 hospitalised COVID-19 patients","volume":"11","author":"Nasser","year":"2023","journal-title":"Intensive Care Med. Exp."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1002\/jmv.26589","article-title":"Evaluation of alpha defensin, IL-1 receptor antagonist, and IL-18 levels in COVID-19 patients with macrophage activation syndrome and acute respiratory distress syndrome","volume":"93","author":"Kerget","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41413-020-0084-5","article-title":"Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: A 15-year follow-up from a prospective cohort study","volume":"8","author":"Zhang","year":"2020","journal-title":"Bone Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1001\/jamainternmed.2020.0994","article-title":"Risk factors associated with acute respiratory distress syndrome and death in patients with Coronavirus Disease 2019 pneumonia in Wuhan, China","volume":"180","author":"Wu","year":"2020","journal-title":"JAMA Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Colarusso, C., Maglio, A., Terlizzi, M., Vitale, C., Molino, A., Pinto, A., Vatrella, A., and Sorrentino, R. (2021). Post-COVID-19 Patients who develop lung fibrotic-like changes have lower circulating levels of IFN-\u03b2 but higher levels of IL-1\u03b1 and TGF-\u03b2. Biomedicines, 9.","DOI":"10.3390\/biomedicines9121931"},{"key":"ref_26","first-page":"2","article-title":"Chest CT Findings in Cases from the Cruise Ship Diamond Princess with Coronavirus Disease (COVID-19)","volume":"2","author":"Inui","year":"2020","journal-title":"Radiol. Cardiothorac. Imaging"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1056\/NEJM198401193100304","article-title":"Interstitial lung diseases of unknown cause. Disorders characterized by chronic inflammation of the lower respiratory tract (first of two parts)","volume":"310","author":"Crystal","year":"1984","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Maddaloni, L., Zullino, V., Bugani, G., Lazzaro, A., Brisciani, M., Mastroianni, C.M., Santinelli, L., and Ruberto, F. (2024). Could SP-A and SP-D serum levels predict COVID-19 severity?. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202402.0739.v2"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"101413","DOI":"10.1016\/j.cocis.2020.101413","article-title":"Exogenous pulmonary surfactant: A review focused on adjunctive therapy for severe acute respiratory syndrome coronavirus 2 including SP-A and SP-D as added clinical marker","volume":"51","author":"Ghati","year":"2021","journal-title":"Curr. Opin. Colloid Interface Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.cca.2022.10.013","article-title":"Surfactant protein D (SP-D) as a biomarker of SARS-CoV-2 infection","volume":"537","author":"Salvioni","year":"2022","journal-title":"Clin. Chim. Acta"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s00408-020-00393-8","article-title":"Are serum interleukin 6 and surfactant protein D levels associated with the clinical course of COVID-19?","volume":"198","author":"Kerget","year":"2020","journal-title":"Lung"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S1074-7613(00)80165-X","article-title":"Chemokines: A new classification system and their role in immunity","volume":"12","author":"Zlotnik","year":"2000","journal-title":"Immunity"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S1359-6101(99)00005-2","article-title":"The MCP\/eotaxin subfamily of CC chemokines","volume":"10","author":"Opdenakker","year":"1999","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bagheri, V., Khorramdelazad, H., Kafi, M., and Abbasifard, M. (2024). Chemokine CCL2 and its receptor CCR2 in different age groups of patients with COVID-19. BMC Immunol., 25.","DOI":"10.1186\/s12865-024-00662-8"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"109325","DOI":"10.1016\/j.intimp.2022.109325","article-title":"Role of CCL2\/CCR2 axis in the pathogenesis of COVID-19 and possible treatments: All options on the table","volume":"113","author":"Ranjbar","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e2578","DOI":"10.1002\/rmv.2578","article-title":"Virus-induced host chemokine CCL2 in COVID-19 pathogenesis: Potential prognostic marker and target of anti-inflammatory strategy","volume":"34","author":"Ansari","year":"2024","journal-title":"Rev. Med. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s10020-020-00230-x","article-title":"IP-10 and MCP-1 as biomarkers associated with disease severity of COVID-19","volume":"26","author":"Chen","year":"2020","journal-title":"Mol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.jmii.2025.02.003","article-title":"Role of CCL2\/CCR2 axis in pulmonary fibrosis induced by respiratory viruses","volume":"58","author":"Li","year":"2025","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"155302","DOI":"10.1016\/j.cyto.2020.155302","article-title":"Prognostic value of interleukin-18 and its association with other inflammatory markers and disease severity in COVID-19","volume":"137","author":"Ozgerb","year":"2021","journal-title":"Cytokine"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1080\/08923973.2023.2215405","article-title":"Targeting the cGAS-STING pathway as an inflammatory crossroad in coronavirus disease 2019 (COVID-19)","volume":"45","author":"Elahi","year":"2023","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_41","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":"ref_42","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1001\/jama.2021.3331","article-title":"Four-month clinical status of a cohort of patients after hospitalization for COVID-19","volume":"325","author":"Morin","year":"2021","journal-title":"JAMA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1038\/s41379-020-0603-3","article-title":"A systematic review of pathological findings in COVID-19: A pathophysiological timeline and possible mechanisms of disease progression","volume":"33","author":"Polak","year":"2020","journal-title":"Med. Pathol."},{"key":"ref_44","unstructured":"(2020). World Health Organization Working Group on the Clinical Characterisation and management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect. Dis., 20, e192\u2013e197."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"501","DOI":"10.7861\/clinmedicine.12-6-501","article-title":"The national early warning score development and implementation group","volume":"12","author":"Newsdig","year":"2012","journal-title":"Clin. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e200047","DOI":"10.1148\/ryct.2020200047","article-title":"Chest CT severity score: An imaging tool for assessing severe COVID-19","volume":"2","author":"Yang","year":"2020","journal-title":"Radiol. Cardiothorac. Imaging"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.jmir.2023.02.003","article-title":"Computed tomography severity score as a predictor of disease severity and mortality in COVID-19 patients: A systematic review and meta-analysis","volume":"54","author":"Prakash","year":"2023","journal-title":"J. Med. Imaging Radiat. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1097\/RLI.0000000000000672","article-title":"The Clinical and Chest CT Features Associated with Severe and Critical COVID-19 Pneumonia","volume":"55","author":"Li","year":"2020","journal-title":"Investig. Radiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4190\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T11:54:48Z","timestamp":1779191688000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":48,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104190"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104190","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,8]]}}}