Int J Biol Sci 2021; 17(6):1565-1573. doi:10.7150/ijbs.58825

Research Paper

Krebs Von den Lungen-6 as a predictive indicator for the risk of secondary pulmonary fibrosis and its reversibility in COVID-19 patients

Mingshan Xue1#, Teng Zhang2#, Hao Chen3#, Yifeng Zeng1, Runpei Lin1, Yingjie Zhen1, Ning Li1, Zhifeng Huang1, Haisheng Hu1, Luqian Zhou1, Hui Wang4, Xiaohua Douglas Zhang2✉, Baoqing Sun1✉

1. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
2. Faculty of Health Sciences, University of Macau. Taipa, Macau, China.
3. Department of Allergy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
4. Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.
# These three authors contributed equally to this work and should be regarded as Joint First Authors.

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Citation:
Xue M, Zhang T, Chen H, Zeng Y, Lin R, Zhen Y, Li N, Huang Z, Hu H, Zhou L, Wang H, Zhang XD, Sun B. Krebs Von den Lungen-6 as a predictive indicator for the risk of secondary pulmonary fibrosis and its reversibility in COVID-19 patients. Int J Biol Sci 2021; 17(6):1565-1573. doi:10.7150/ijbs.58825. Available from https://www.ijbs.com/v17p1565.htm

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Abstract

Dysregulated immune response and abnormal repairment could cause secondary pulmonary fibrosis of varying severity in COVID-19, especially for the elders. The Krebs Von den Lungen-6 (KL-6) as a sensitive marker reflects the degree of fibrosis and this study will focus on analyzing the evaluative efficacy and predictive role of KL-6 in COVID-19 secondary pulmonary fibrosis. The study lasted more than three months and included total 289 COVID-19 patients who were divided into moderate (n=226) and severe groups (n=63) according to the severity of illness. Clinical information such as inflammation indicators, radiological results and lung function tests were collected. The time points of nucleic acid test were also recorded. Furthermore, based on Chest radiology detection, it was identified that 80 (27.7%) patients developed reversible pulmonary fibrosis and 34 (11.8%) patients developed irreversible pulmonary fibrosis. Receiver operating characteristic (ROC) curve analysis shows that KL-6 could diagnose the severity of COVID-19 (AUC=0.862) and predict the occurrence of pulmonary fibrosis (AUC = 0.741) and irreversible pulmonary fibrosis (AUC=0.872). Importantly, the cross-correlation analysis demonstrates that KL-6 rises earlier than the development of lung radiology fibrosis, thus also illuminating the predictive function of KL-6. We set specific values (505U/mL and 674U/mL) for KL-6 in order to assess the risk of pulmonary fibrosis after SARS-CoV-2 infection. The survival curves for days in hospital show that the higher the KL-6 levels, the longer the hospital stay (P<0.0001). In conclusion, KL-6 could be used as an important predictor to evaluate the secondary pulmonary fibrosis degree for COVID-19.

Keywords: Krebs von den Lungen-6, Coronavirus disease 2019, Pulmonary fibrosis