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

J Med Virol. 2020 Oct;92(10):2216-2220. doi: 10.1002/jmv.26087. Epub 2020 Jun 9.


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.

Keywords: COVID-19; KL-6; biomarker; prognosis.

MeSH terms

  • Aged
  • Biomarkers / blood*
  • COVID-19 / blood*
  • COVID-19 / diagnosis*
  • COVID-19 / immunology
  • COVID-19 / virology
  • Female
  • Humans
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / virology
  • Lung / immunology
  • Lung / virology
  • Male
  • Middle Aged
  • Mucin-1 / blood*
  • Pandemics
  • Prognosis
  • ROC Curve
  • SARS-CoV-2 / pathogenicity


  • Biomarkers
  • MUC1 protein, human
  • Mucin-1