Volume 25, Issue 6 (11-2021)                   IBJ 2021, 25(6): 381-389 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Witarto A P, Witarto B S, Putra A J E, Pramudito S L, Rosyid A N. Serum Krebs von den Lungen-6 for Predicting the Severity of COVID-19 Lung Injury: A Systematic Review and Meta-Analysis. IBJ 2021; 25 (6) :381-389
URL: http://ibj.pasteur.ac.ir/article-1-3472-en.html
Introduction: Lung injury is common in coronavirus disease 2019 (COVID-19) patients. The severity of lung injury appears to be reflected in serum Krebs von den Lungen-6 (KL-6), a glycoprotein expressed on type II alveolar epithelium. This study aims to assess the role of serum KL-6 in reflecting the severity of lung injury in COVID-19 patients. Methods: A systematic search was conducted in Scopus, PubMed, Wiley Online Library, and ProQuest. Articles were screened based on several eligibility criteria and assessed for study quality using Newcastle-Ottawa Scale. Results: This systematic review included four studies involving a total of 151 adult COVID-19 patients. Pooled analysis revealed that serum KL-6 was significantly higher in severe patients (SMD = 1.16; 95% CI = 0.69–1.63) with moderately high pooled sensitivity (79%; 95% CI = 61–91%) and specificity (86%; 95% CI = 72–95%). Conclusion: High serum KL-6 may depict more severe lung injury in COVID-19 patients with moderately high sensitivity and specificity.
Type of Study: Full Length/Original Article | Subject: Related Fields

1. World Health Organization. Clinical management of COVID-19: interim guidance. World health organization 2020; Avaiable at: https:// creativecommons.org/licenses/by-nc-sa/3.0/igo/deed.ar
2. Liu M, Wang T, Zhou Y, Zhao Y, Zhang Y, Li J. Potential role of ACE2 in coronavirus disease 2019 (COVID-19) prevention and management. Journal of translational internal medicine 2020; 8(1): 9-19. [DOI:10.2478/jtim-2020-0003]
3. World Health Organization. Public health surveillance for COVID-19: Interim guidance. World health organization 2020; Available at: https://www.who. int/publications/i/item/who-2019-nCoV-surveillance guidance-2020.8.
4. Carasana L, Sonzogni A, Nasr A, Rossi RS, Pellegrinelli A, Zerbi P, Rech R, Colombo R, Antinori S, Corbellino M, Galli M, Catena E, Tosoni A, Gianatti A, Nebuloni M. Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study. The lancet infectious diseases 2020; 20(10): 1135-1140. [DOI:10.1016/S1473-3099(20)30434-5]
5. Ma H, Lu J, Song Y, Wang H, Yin S. The value of serum Krebs von den lungen-6 as a diagnostic marker in connective tissue disease associated with interstitial lung disease. BMC pulmonary medicine 2020; 20(6): 1-8. [DOI:10.1186/s12890-019-1043-z]
6. Miyazaki K, Kurishima K, Kagohashi K, Kawaguchi M, Ishikawa H, Satoh H, Hizawa N. Serum KL-6 levels in lung cancer patients with or without interstitial lung disease. Journal of clinical laboratory analysis 2010; 24(5): 295-299. [DOI:10.1002/jcla.20404]
7. Ohshimo S, Ishikawa N, Horimasu Y, Hattori N, Horhashi N, Tanigawa K, Kohno N, Bonella F, Guzman J, Costabel U. Baseline KL-6 predicts increased risk for acute exacerbation of idiopathic pulmonary fibrosis. Respiratory medicine 2014; 108(7): 1031-1039. [DOI:10.1016/j.rmed.2014.04.009]
8. Zheng P, Liu X, Huang H, Guo Z, Wu G, Hu H, Cai C, Luo W, Nili W, Han Q, Sun B. Diagnostic value of KL-6 in idiopathic interstitial pneumonia. Journal of thoracic disease 2018; 10(8): 4724-4732. [DOI:10.21037/jtd.2018.07.54]
9. Kim HC, Choi KH, Jacob J, Song JW. Prognostic role of blood KL-6 in rheumatoid arthritis-associated interstitial lung disease. PLoS one 2020: 15(3): 1-13. [DOI:10.1371/journal.pone.0229997]
10. Xue M, Zheng P, Bian X, Huang Z, Huang H, Zeng Y, Hu H, Liu X, Zhou L, Sun B, Wu J, Zhong N. Exploration and correlation analysis of changes in Krebs von den Lungen-6 levels in COVID-19 patients with different types in China. BioScience trends 2020; 14(4): 290-296. [DOI:10.5582/bst.2020.03197]
11. Awano N, Inomata M, Kuse N, Tone M, Takada K, Muta Y, Fujimoto K, Akagi Y, Mawatari M, Ueda A, Izumo T. Serum KL-6 level is a useful biomarker for evaluating the severity of coronavirus disease 2019. Respiratory investigation 2020; 58(6): 440-447. [DOI:10.1016/j.resinv.2020.07.004]
12. Moher D, Liberati A, Tetzlaff A, Altman DG. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA statement. PLoS medicine 2009; 6(7): e1000097. [DOI:10.1371/journal.pmed.1000097]
13. Shi J, Luo D, Weng H, Zeng X, Lin L, Chu H, Tong T. Optimally estimating the sample standard deviation from the five-number summary. Research synthesis methods 2020; 11(5): 641-654. [DOI:10.1002/jrsm.1429]
14. Zamora J, Abraira V, Muriel A, Khan K, Coomarasamy A. Meta-DiSc: a software for meta-analysis of test accuracy data. BMC medical research methodology 2006; 6: 31. [DOI:10.1186/1471-2288-6-31]
15. d'Alessandro M, Bergantini L, Cameli P, Curatola G, Remediani L, Sestini P, Bargagli E. Peripheral biomarkers' panel for severe COVID-19 patients. Journal of medical virology 2020; 93(3): 1-3. [DOI:10.1002/jmv.26577]
16. d'Alessandro M, Cameli P, Refini RM, Bergantini L, Alonzi V, Lanzarone N, Bennett D, Rana GD, Montagnani F, Scolleta S, Franchi F, Frediani B, Valente S, Mazzei MA, Bonella F, Bargagli E. Serum KL-6 concentrations as a novel biomarker of severe COVID-19. Journal medical virology 2020; 92(10): 1-5. [DOI:10.1002/jmv.26087]
17. Power M, Fell G, Wright M. Principles for high-quality, high-value testing. Evidence-based medicine 2013; 18(1): 5-10. [DOI:10.1136/eb-2012-100645]
18. Qin H, Xu XP, Zou J, Zhao XJ, Wu HW, Zha QF, Chen S, Kang Y, Jiang HD. Krebns von den Lungen-6 associated with chest high-resolution CT score in evaluation severity of patients with interstitial lung disease. Pulmonology 2019; 25(3): 143-148. [DOI:10.1016/j.pulmoe.2018.05.008]
19. Hu Y, Wang L, Jin Y, Du S, Du Y, He X, Weng D, Zhou Y, Li Q, Shen L, Zhang F, Su Y, Sun X, Ding J, Zhang W, Cai H, Dai H, Dai J, Li H. Serum Krebs von den Lungen-6 level as a diagnostic biomarker for interstitial lung disease in Chinese patients. Clinical respiratory journal 2017; 11(3): 337-345. [DOI:10.1111/crj.12341]
20. Jee AS, Sahhar J, Youssef P, Bleasel P, Adelstein S, Nguyen M, Corte TJ. Review: Serum biomarkers in idiopathic pulmonary fibrosis and systemic sclerosis associated interstitial lung disease-frontiers and horizons. Pharmacology and therapeutics 2019; 202: 40-52. [DOI:10.1016/j.pharmthera.2019.05.014]
21. Hisata S, Kimura Y, Shibata N, Ono S, Kobayashi T, Chiba S, Ohta H, Nukiwa T, Ebina M. A normal range of KL-6/MUC1 independent of elevated SP-D indicated a better prognosis in the patients with honeycombing on High-Resolution computed tomography. Pulmonary medicine 2011; 2011: 1-7. [DOI:10.1155/2011/806014]
22. Menon B, Tiwari M, Gopi A, Raj P, Panwar K. Serum krebs von den lungen-6 (KL-6): a promising biomarker in sarcoidosis. MOJ current research and reviews 2018; 1(2): 45-47. [DOI:10.15406/mojcrr.2018.01.00009]
23. Determann RM, Royakkers AANM, Haitsma JJ, Zhang H, Slutsky AS, Ranieri VM, Schultz MJ. Plasma levels of surfactant protein D and KL-6 for evaluation of lung injury in critically ill mechanically ventilated patients. BMC pulmonary medicine 2010; 10: 6. [DOI:10.1186/1471-2466-10-6]
24. Gassas A, Schechter T, Krueger J, Craig-Barnes H, Sung L, Ali M, Dell S, Egeler RM, Zaidman I, Palaniyar N. Serum Krebs Von Den Lungen-6 as a biomarker for early detection of bronchiolitis obliterans syndrome in children undergoing allogeneic stem cell transplantation. Biol blood marrow transplant 2015; 21:1524-1531. [DOI:10.1016/j.bbmt.2015.04.021]
25. Kumánovics G, Görbe É, Minier T, Simon D, Berki T, Czirják L. Follow-up of serum KL-6 lung fibrosis biomarker levels in 173 patients with systemic sclerosis. Clinical exprimental rheumatology 2014; 32 (Suppl. 86): S138-S144.
26. Zeng H, Chen D, Yan J, Yang Q, Han Q, Li S, Cheng L. Proteomic characteristics of bronchoalveolar lavage fluid in critical COVID-19 patients. FEBS Journal 2020; 288(17): 1-25. [DOI:10.1111/febs.15609]
27. Nakamura H, Miyagi K, Otsuki M, Higure Y, Nishiyama N, Kinjo T, Nakamatsu M, Haranaga S, Tateyama M, Fujita J. Serum KL-6 can distinguish between different phenotypes of severe COVID-19. Journal medical virology 2021; 93(1): 158-160. [DOI:10.1002/jmv.26268]
28. Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, Camporota L COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive care medicin 2020; 46(6): 1099-1102. [DOI:10.1007/s00134-020-06033-2]

Add your comments about this article : Your username or Email:

Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2024 CC BY-NC 4.0 | Iranian Biomedical Journal

Designed & Developed by : Yektaweb