Correlation of Krebs von den Lungen-6 and fibronectin with pulmonary fibrosis in coronavirus disease 2019

Abstract

Objective Coronavirus Disease 2019 (COVID-19) caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still spreading worldwide, which may progress to pulmonary fibrosis (PF), leading to the worsen outcome. As the markers of lung injury, the correlation of Krebs von den Lungen-6 (KL-6) and fibronectin (Fn) with pulmonary fibrosis in COVID-19 was still unclear. Methods 113 patients diagnosed as COVID-19 were enrolled in this retrospective study, and divided into three categories as mild, moderate and severe cases. The concentrations of serum KL-6 and Fn at hospital admission were tested using the method of latex agglutination assay and immunoturbidimetic assay, respectively. Results Compared with that in the non-severe COVID-19 cases and normal control subjects, serum KL-6 concentrations on admission were significantly higher in the severe group, which was positively correlated with C-reactive protein, and negatively correlated with lymphocytes count. Whereas, no obvious elevation in serum Fn concentration was investigated in COVID-19 patients with the different phenotypes. The severe cases displayed the higher incident rate of pulmonary fibrosis at hospital discharge. Compared with non-PF patients, the COVID-19 cases with PF have the higher serum KL-6 values. Conclusion Serum KL-6 concentration was significantly elevated in severe COVID-19 patients, which may be useful for evaluating the disease severity. For early prevention of the development of pulmonary fibrosis, high concentrations of serum KL-6 in the early stage of COVID-19 should be paid close attention.

The Potential of Lung Epithelium Specific Proteins as Biomarkers for COVID-19-Associated Lung Injury

“…Thus, high serum concentrations of KL-6 might predict the pulmonary fibrotic sequelae in COVID-19 patients. Peng et al found that serum KL-6 levels in COVID-19 patients who developed pulmonary fibrosis were higher than those who did not develop pulmonary fibrosis [ 33 ]. In the same study, the prevalence rate of pulmonary fibrosis in severe COVID-19 cases was much higher than in non-severe cases, indicating that high KL-6 levels in serum in severe COVID-19 cases may be a useful biomarker for predicting lung fibrosis [ 33 ].…”

Krebs von den Lungen-6 (KL-6) as a clinical marker for severe COVID-19: A systematic review and meta-analyses

“…The full text of 33 remained studies was assessed for eligibility and 12 case reports or case series ( Horii et al, 2020 ; Inoue et al, 2020 ; Ito et al, 2020 ; Nakamura et al, 2020 ; Scarpati, 2020 , Shibata et al, 2020 ; Shimazu et al, 2020 ; Zeng et al, 2020a ; Fukada et al, 2021 ; Sumimoto et al, 2021 ; Suzuki et al, 2021 ; Yamaya et al, 2021 ), 2 studies that did not report the results clearly ( Miyagami et al, 2021 ; Takeshita et al, 2021 ), 3 studies that did not classify patients based on disease severity ( Frix et al, 2020 ; Chen et al, 2021a ; Scotto et al, 2021 ) and 1 preprint study ( Alimova et al, 2020 ) were excluded. Finally, 15 studies identified as relevant and entered the quality assessment ( Awano et al, 2020 , d'Alessandro et al, 2020a , d'Alessandro and Cameli, 2020 , d'Alessandro et al, 2020b ; Frix et al, 2020 ; jp, 2020 , Saito et al, 2020 ; Wang et al, 2020 ; Xue et al, 2020 ; Anai et al, 2021 ; Bergantini et al, 2021 ; Chen et al, 2021 , d’Alessandro et al, 2021 ; Deng et al, 2021 ; He et al, 2021 ; Peng et al, 2021 ; Scotto et al, 2021 ). Ultimately, 7 studies (1 cross-sectional and 6 case-control studies) met the inclusion criteria of this systematic review ( Awano et al, 2020 , d'Alessandro et al, 2020b ; Saito et al, 2020 ; Bergantini et al, 2021 ; Deng et al, 2021 ; He et al, 2021 ; Peng et al, 2021 ) ( Table 1 ).…”

Pulmonary fibrosis from molecular mechanisms to therapeutic interventions: lessons from post-COVID-19 patients

“…For instance, one important biomarker for ILDs is represented by Krebs von den Lungen-6 (KL6), a glycoprotein classified as human MUC1 mucin: specifically, the MUC1 extracellular region contains the KL-6 epitope domain, which is cleaved from the cell surface in response to injury and released into the surrounding environment [186] . Indeed, increased concentrations of serum KL-6 have been correlated with lung epithelial damage, involved in interstitial lung disease including IPF, caused by damaged AT2 pneumocytes [187] , [188] . To this regard, it has been demonstrated that KL-6 concentrations were increased in COVID-19 patients with fibrotic lung alterations than in the non-fibrotic group; in particular, COVID-19 patients, who developed severe persistent fibrotic lung complications at HRCT, showed persistent high levels of KL-6 during the follow-up [189] .…”

“…To this regard, it has been demonstrated that KL-6 concentrations were increased in COVID-19 patients with fibrotic lung alterations than in the non-fibrotic group; in particular, COVID-19 patients, who developed severe persistent fibrotic lung complications at HRCT, showed persistent high levels of KL-6 during the follow-up [189] . Thus, high concentrations of serum KL-6 in the early stage of COVID-19 should be highly taken into account for the early prevention of PF development [188] .…”