Serum KL-6 level is a useful biomarker for evaluating the severity of coronavirus disease 2019

Abstract

Background Coronavirus disease 2019 (COVID-19) is currently spreading worldwide. This study examined whether serum Krebs von den Lungen-6 (KL-6) level is a useful biomarker for evaluating the severity of COVID-19. Methods We retrospectively examined patients diagnosed with COVID-19 at the Japanese Red Cross Medical Center between February 1, 2020, and May 15, 2020. Patients were divided into four categories based on clinical and radiological findings: mild, moderate, severe, and critical. Patients who presented with a mild or moderate illness and patients who started with or worsened to a severe or critical illness were classified as the non-severe and severe groups, respectively. The two groups were compared for patient characteristics, including serum KL-6 levels. Receiver operating characteristic curves were used to define the optimum cut-off value of serum KL-6 level to evaluate COVID-19 severity. Results A total of 54 patients were enrolled, including 33 in the non-severe group and 21 in the severe group, of which four died. Compared with those in the non-severe group, more patients in the severe group were significantly older and had comorbidities. Serum KL-6 levels were significantly higher in the severe group than in the non-severe group both at diagnosis (median, 338 U/mL) and at peak levels within one week after diagnosis (median, 781 U/mL) (both p < 0.001). Serum KL-6 value at peak level (371 U/mL) was used as the optimal cut-off to evaluate disease severity (sensitivity, 85.7%; specificity, 96.6%). Conclusions Serum KL-6 levels were significantly elevated in severe COVID-19 and is useful for evaluating its severity.

Risk factors for severe and critically ill COVID‐19 patients: A review

“…KL‐6 is mainly produced by damaged or regenerating alveolar type II pneumocytes 39 . Both baseline or peak serum KL‐6 levels were higher in critical and severe COVID‐19 cases than in nonsevere cases 225 . Consistently, another study also demonstrated higher serum concentrations of KL‐6 in severe patients than in nonsevere patients, with a cutoff value of 406.5 U/ml 39 .…”

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

“…On the other hand, the elevated serum KL-6 may be also related to the more severe lung injury occurring in the severe COVID-19 patients. The previous studies have reported that serum KL-6 may be used to evaluate the severity of COVID-19 [14] , [30] . A very recent study also reported that serum KL-6 may be a novel biomarker for accessing COVID-19 severity and predicting the prognosis of lung injury [31] .…”

“…A recent study reported that there is a complexity of interactions between coexisting idiopathic pulmonary fibrosis/ILD and COVID-19 disease [6] . Serum KL-6 has been suggested to be a useful biomarker for evaluating the severity of COVID-19, however, the results from another research did not demonstrate that KL-6 can discriminate different ventilatory phenotypes in COVID-19 patients [14] , [15] , [16] . Moreover, pulmonary fibrosis is identified by excessive deposition of extracellular matrix (ECM) proteins, such as fibronectin (Fn) [17] .…”

Serial KL-6 measurements in COVID-19 patients

“…Moreover, KL-6 has been also proposed as bioindicator of acute respiratory distress syndrome (ARDS) and infective pneumonia (ref). Since the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, KL-6 has also been proposed as a prognostic marker for this disease [6][7][8][9]. The pathogenesis of COVID-19 (as the lung disease caused by SARS-CoV-2 is defined) is not entirely clear [10], although it is postulated that elevated serum concentrations of proinflammatory cytokines and oxidative…”