Serum KL‐6 concentrations as a novel biomarker of severe COVID‐19

Severe acute respiratory syndrome coronavirus 2–induced direct cytopathic effects against type I and II pneumocytes mediate lung damage. Krebs von den Lungen‐6 (KL‐6) is mainly produced by damaged or regenerating alveolar type II pneumocytes. This preliminary study analyzed serum concentrations of KL‐6 in patients with coronavirus disease (COVID‐19) to verify its potential as a prognostic biomarker of severity. Twenty‐two patients (median age [interquartile range] 63 [59‐68] years, 16 males) with COVID‐19 were enrolled prospectively. Patients were divided into mild‐moderate and severe groups, according to respiratory impairment and clinical management. KL‐6 serum concentrations and lymphocyte subset were obtained. Peripheral natural killer (NK) cells/µL were significantly higher in nonsevere patients than in the severe group (P = .0449) and the best cut‐off value was 119 cells/µL. KL‐6 serum concentrations were significantly higher in severe patients than the nonsevere group (P = .0118). Receiver operating characteristic analysis distinguished severe and nonsevere patients according to KL‐6 serum levels and the best cut‐off value was 406.5 U/mL. NK cell analysis and assay of KL‐6 in serum can help identify severe COVID‐19 patients. Increased KL‐6 serum concentrations were observed in patients with severe pulmonary involvement, revealing a prognostic value and supporting the potential usefulness of KL‐6 measurement to evaluate COVID‐19 patients' prognosis.

[1]  D. Bennett,et al.  Peripheral lymphocyte subset monitoring in COVID19 patients: a prospective Italian real-life case series. , 2020, Minerva medica.

[2]  E. Bargagli,et al.  Serum KL‐6 levels in pulmonary Langerhans’ cell histiocytosis , 2020, European journal of clinical investigation.

[3]  M. Mazzei,et al.  Bronchoalveolar lavage and serum KL-6 concentrations in chronic hypersensitivity pneumonitis: correlations with radiological and immunological features , 2020, Internal and Emergency Medicine.

[4]  E. Bargagli,et al.  BAL biomarkers’ panel for differential diagnosis of interstitial lung diseases , 2020, Clinical and Experimental Medicine.

[5]  S. Homma,et al.  Serial change in serum biomarkers during treatment of Non-HIV Pneumocystis pneumonia. , 2019, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy.

[6]  D. Bennett,et al.  Serial KL-6 analysis in patients with idiopathic pulmonary fibrosis treated with nintedanib. , 2019, Respiratory investigation.

[7]  E. Lee,et al.  Serum KL-6 levels reflect the severity of interstitial lung disease associated with connective tissue disease , 2019, Arthritis Research & Therapy.

[8]  M. Hosoya,et al.  Serum KL‐6 levels as a biomarker of lung injury in respiratory syncytial virus bronchiolitis , 2009, Journal of Medical Virology.

[9]  Y. Ohtsuki,et al.  Clinical utility of serum beta-D-glucan and KL-6 levels in Pneumocystis jirovecii pneumonia. , 2009, Internal medicine.

[10]  T. Evans,et al.  KL‐6 levels are elevated in plasma from patients with acute respiratory distress syndrome , 2004, European Respiratory Journal.

[11]  K. Hisata,et al.  Clinical significance of the serum surfactant protein D and KL-6 levels in patients with measles complicated by interstitial pneumonia , 2001, European Journal of Pediatrics.