[en] ("[en] BACKGROUND: The global coronavirus disease 2019 (COVID-19) has presented significant challenges and created concerns worldwide. Besides, patients who have experienced a SARS-CoV-2 infection could present post-viral complications that can ultimately lead to pulmonary fibrosis. Serum levels of Krebs von den Lungen 6 (KL-6), high molecular weight human MUC1 mucin, are increased in the most patients with various interstitial lung damage. Since its production is raised during epithelial damages, KL-6 could be a helpful non-invasive marker to monitor COVID-19 infection and predict post-infection sequelae.
METHODS: We retrospectively evaluated KL-6 levels of 222 COVID-19 infected patients and 70 healthy control. Serum KL-6, fibrinogen, lactate dehydrogenase (LDH), platelet-lymphocytes ratio (PLR) levels and other biological parameters were analyzed. This retrospective study also characterized the relationships between serum KL-6 levels and pulmonary function variables.
RESULTS: Our results showed that serum KL-6 levels in COVID-19 patients were increased compared to healthy subjects (470 U/ml vs 254 U/ml, P <0.00001). ROC curve analysis enabled us to identify that KL-6 > 453.5 U/ml was associated with COVID-19 (AUC = 0.8415, P < 0.0001). KL-6 level was positively correlated with other indicators of disease severity such as fibrinogen level (r = 0.1475, P = 0.0287), LDH level (r = 0,31, P = 0,004) and PLR level (r = 0.23, P = 0.0005). However, KL-6 levels were not correlated with pulmonary function tests (r = 0.04, P = 0.69).
CONCLUSIONS: KL-6 expression was correlated with several disease severity indicators. However, the association between mortality and long-term follow-up outcomes needs further investigation. More extensive trials are required to prove that KL-6 could be a marker of disease severity in COVID-19 infection.","[en] ","")
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Cambier, Maureen ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Henket, Monique ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Frix, Anne-Noëlle ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Gofflot, Stéphanie ; Centre Hospitalier Universitaire de Liège - CHU > > Biothèque Hospitalo-Universitaire de Liège (BHUL)
THYS, Marie ; Centre Hospitalier Universitaire de Liège - CHU > > Service des informations médico économiques (SIME)
Tomasetti, Sara; Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
Peired, Anna ; Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy
Struman, Ingrid ; Université de Liège - ULiège > GIGA > GIGA Cancer - Molecular Angiogenesis Laboratory
Rousseau, Anne-Françoise ; Centre Hospitalier Universitaire de Liège - CHU > > Service des soins intensifs
Misset, Benoît ; Centre Hospitalier Universitaire de Liège - CHU > > Service des soins intensifs
Darcis, Gilles ; Centre Hospitalier Universitaire de Liège - CHU > > Service des maladies infectieuses - médecine interne
Moutschen, Michel ; Centre Hospitalier Universitaire de Liège - CHU > > Service des maladies infectieuses - médecine interne
Louis, Renaud ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Njock, Makon-Sébastien ; Centre Hospitalier Universitaire de Liège - CHU > > Service de rhumatologie
Cavalier, Etienne ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chimie clinique
Guiot, Julien ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. New England Journal of Medicine. 2020; 382: 727–733. https://doi.org/10.1056/NEJMoa2001017 PMID: 31978945
Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, et al. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020; 382: 929–936. https://doi.org/10.1056/NEJMoa2001191 PMID: 32004427
Tang D, Comish P, Kang R. The hallmarks of COVID-19 disease. Hobman TC, editor. PLoS Pathog. 2020; 16: e1008536. https://doi.org/10.1371/journal.ppat.1008536 PMID: 32442210
Huang W-H, Teng L-C, Yeh T-K, Chen Y-J, Lo W-J, Wu M-J, et al. 2019 novel coronavirus disease (COVID-19) in Taiwan: Reports of two cases from Wuhan, China. J Microbiol Immunol Infect. 2020; 53: 481–484. https://doi.org/10.1016/j.jmii.2020.02.009 PMID: 32111449
Frix A, Schoneveld L, Ladang A, Henket M, Duysinx B, Vaillant F, et al. Could KL-6 levels in COVID-19 help to predict lung disease? Respiratory Research. Respir Res; 2020. https://doi.org/10.1186/s12931-020-01560-4 PMID: 33234132
Guiot J, Henket M, Frix AN, Delvaux M, Denis A, Giltay L, et al. Single-center experience of patients with interstitial lung diseases during the early days of the COVID-19 pandemic. Respir Investig. 2020; 58: 437–439. https://doi.org/10.1016/j.resinv.2020.08.006 PMID: 32978099
Schoneveld L, Ladang A, Henket M, Frix A-N, Cavalier E, Guiot J, et al. YKL-40 as a new promising prognostic marker of severity in COVID infection. Crit Care. 2021; 25: 66. https://doi.org/10.1186/s13054-020-03383-7 PMID: 33593373
Defêche J, Azarzar S, Mesdagh A, Dellot P, Tytgat A, Bureau F, et al. In-Depth Longitudinal Comparison of Clinical Specimens to Detect SARS-CoV-2. Pathogens. 2021; 10: 1362. https://doi.org/10.3390/pathogens10111362 PMID: 34832518
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020; 181: 271–280.e8. https://doi.org/10.1016/j.cell.2020.02.052 PMID: 32142651
Venkataraman T, Coleman CM, Frieman MB. Overactive Epidermal Growth Factor Receptor Signaling Leads to Increased Fibrosis after Severe Acute Respiratory Syndrome Coronavirus Infection. J Virol. 2017;91. https://doi.org/10.1128/JVI.00182-17 PMID: 28404843
Guiot J, Moermans C, Henket M, Corhay JL, Louis R. Blood Biomarkers in Idiopathic Pulmonary Fibrosis. Lung. Lung; 2017. pp. 273–280. https://doi.org/10.1007/s00408-017-9993-5 PMID: 28353114
Inoue Y, Kaner RJ, Guiot J, Maher TM, Tomassetti S, Moiseev S, et al. Diagnostic and Prognostic Biomarkers for Chronic Fibrosing Interstitial Lung Diseases With a Progressive Phenotype. Chest. 2020; 158: 646–659. https://doi.org/10.1016/j.chest.2020.03.037 PMID: 32268131
Bonhomme O, André B, Gester F, de Seny D, Moermans C, Struman I, et al. Biomarkers in systemic sclerosis-associated interstitial lung disease: review of the literature. Rheumatology (Oxford). 2019; 58: 1534–1546. https://doi.org/10.1093/rheumatology/kez230 PMID: 31292645
Ohshimo S, Yokoyama A, Hattori N, Ishikawa N, Hirasawa Y, Kohno N. KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts. Biochem Biophys Res Commun. 2005; 338: 1845–1852. https://doi.org/10.1016/j.bbrc.2005.10.144 PMID: 16289035
Hirasawa Y, Kohno N, Yokoyama A, Inoue Y, Abe M, Hiwada K. KL-6, a human MUC1 mucin, is chemo-tactic for human fibroblasts. Am J Respir Cell Mol Biol. 1997; 17: 501–7. https://doi.org/10.1165/ajrcmb.17.4.2253 PMID: 9376125
Ohnishi H, Yokoyama A, Yasuhara Y, Watanabe A, Naka T, Hamada H, et al. Circulating KL-6 levels in patients with drug induced pneumonitis. Thorax. 2003; 58: 872. https://doi.org/10.1136/thorax.58.10. 872 PMID: 14514942
Kohno N, Awaya Y, Oyama T, Yamakido M, Akiyama M, Inoue Y, et al. KL-6, a mucin-like glycoprotein, in bronchoalveolar lavage fluid from patients with interstitial lung disease. Am Rev Respir Dis. 1993; 148: 637–42. https://doi.org/10.1164/ajrccm/148.3.637 PMID: 8368634
Ishizaka A, Matsuda T, Albertine KH, Koh H, Tasaka S, Hasegawa N, et al. Elevation of KL-6, a lung epithelial cell marker, in plasma and epithelial lining fluid in acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol. 2004; 286: 1088–1094. https://doi.org/10.1152/ajplung.00420.2002 PMID: 12959931
Bagoly Z, Szegedi I, Kálmándi R, Tóth NK, Csiba L. Markers of Coagulation and Fibrinolysis Predicting the Outcome of Acute Ischemic Stroke Thrombolysis Treatment: A Review of the Literature. Front Neurol. 2019; 10: 513. https://doi.org/10.3389/fneur.2019.00513 PMID: 31316444
Åttingsberg E, Hoyer N, Wilcke T, Prior TS, Bendstrup E, Shaker S. Lactate dehydrogenase as a biomarker of advanced disease in idiopathic pulmonary fibrosis. Idiopathic interstitial pneumonias. European Respiratory Society; 2019. p. PA4701. https://doi.org/10.1183/13993003.congress-2019. PA4701
Simadibrata DM, Pandhita BAW, Ananta ME, Tango T. Platelet-to-lymphocyte ratio, a novel biomarker to predict the severity of COVID-19 patients: A systematic review and meta-analysis. J Intensive Care Soc. 2020 [cited 10 Nov 2021]. https://doi.org/10.1177/1751143720969587
He JL, Luo L, Luo ZD, Lyu JX, Ng MY, Shen XP, et al. Diagnostic performance between CT and initial real-time RT-PCR for clinically suspected 2019 coronavirus disease (COVID-19) patients outside Wuhan, China. Respir Med. 2020; 168: 105980. https://doi.org/10.1016/j.rmed.2020.105980 PMID: 32364959
Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN, et al. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell. 2020; 181: 1016-1035.e19. https://doi.org/10.1016/j.cell.2020.04. 035 PMID: 32413319
Sato H, Callister MEJ, Mumby S, Quinlan GJ, Welsh KI, DuBois RM, et al. KL-6 levels are elevated in plasma from patients with acute respiratory distress syndrome. European Respiratory Journal. 2004; 23: 142–145. https://doi.org/10.1183/09031936.03.00070303 PMID: 14738246
Kondo T, Hattori N, Ishikawa N, Murai H, Haruta Y, Hirohashi N, et al. KL-6 concentration in pulmonary epithelial lining fluid is a useful prognostic indicator in patients with acute respiratory distress syndrome. Respir Res. 2011; 12: 1–7. https://doi.org/10.1186/1465-9921-12-32/FIGURES/4
Xue M, Zheng P, Bian X, Huang Z, Huang H, Zeng Y, et al. Exploration and correlation analysis of changes in Krebs von den Lungen-6 levels in COVID-19 patients with different types in China. Biosci Trends. 2020; 14: 290–296. https://doi.org/10.5582/bst.2020.03197 PMID: 32565512
Awano N, Inomata M, Kuse N, Tone M, Takada K, Muto Y, et al. Serum KL-6 level is a useful biomarker for evaluating the severity of coronavirus disease 2019. Respir Investig. 2020; 58: 440–447. https://doi.org/10.1016/j.resinv.2020.07.004 PMID: 32863199
Han H, Yang L, Liu R, Liu F, Liu F, Wu KL, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020; 58: 1116–1120. https://doi.org/10.1515/cclm-2020-0188 PMID: 32172226
Kim S, Nadel JA. Fibrinogen binding to ICAM-1 promotes EGFR-dependent mucin production in human airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2009; 297: L174–83. https://doi.org/10.1152/ajplung.00032.2009 PMID: 19429776
Patra T, Meyer K, Geerling L, Isbell TS, Hoft DF, Brien J, et al. SARS-CoV-2 spike protein promotes IL-6 trans-signaling by activation of angiotensin II receptor signaling in epithelial cells. PLoS Pathog. 2020;16. https://doi.org/10.1371/journal.ppat.1009128 PMID: 33284859
Qu R, Ling Y, Zhang Y hui zhi, Wei L ya, Chen X, Li X mian, et al. Platelet-to-lymphocyte ratio is associated with prognosis in patients with coronavirus disease-19. J Med Virol. 2020; 92: 1533–1541. https://doi.org/10.1002/jmv.25767 PMID: 32181903
Gong J, Ou J, Qiu X, Jie Y, Chen Y, Yuan L, et al. A tool for early prediction of severe coronavirus disease 2019 (covid-19): A multicenter study using the risk nomogram in Wuhan and Guangdong, China. Clinical Infectious Diseases. 2020; 71: 833–840. https://doi.org/10.1093/cid/ciaa443 PMID: 32296824
Henry BM, Aggarwal G, Wong J, Benoit S, Vikse J, Plebani M, et al. Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: A pooled analysis. Am J Emerg Med. 2020; 38: 1722–1726. https://doi.org/10.1016/j.ajem.2020.05.073 PMID: 32738466
Chiang CH, Shih JF, Su WJ, Perng RP. Eight-month prospective study of 14 patients with hospital-acquired severe acute respiratory syndrome. Mayo Clin Proc. 2004; 79: 1372–1379. https://doi.org/10.4065/79.11.1372 PMID: 15544014
RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021; 384: 693–704. https://doi.org/10.1056/NEJMoa2021436 PMID: 32678530
Scotto R, Pinchera B, Perna F, Atripaldi L, Giaccone A, Sequino D, et al. Serum KL-6 Could Represent a Reliable Indicator of Unfavourable Outcome in Patients with COVID-19 Pneumonia. Int J Environ Res Public Health. 2021; 18: 2078. https://doi.org/10.3390/ijerph18042078 PMID: 33672761
Similar publications
Sorry the service is unavailable at the moment. Please try again later.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.
