Krebs von den Lungen 6 (KL-6) as a marker for disease severity and persistent radiological abnormalities following COVID-19 infection at 12 weeks

PLoS One. 2021 Apr 29;16(4):e0249607. doi: 10.1371/journal.pone.0249607. eCollection 2021.


Introduction: Acute presentations of COVID-19 infection vary, ranging from asymptomatic carriage through to severe clinical manifestations including acute respiratory distress syndrome (ARDS). Longer term sequelae of COVID-19 infection includes lung fibrosis in a proportion of patients. Krebs von den Lungen 6 (KL-6) is a mucin like glycoprotein that has been proposed as a marker of pulmonary epithelial cell injury. We sought to determine whether KL-6 was a marker of 1) the severity of acute COVID-19 infection, or 2) the persistence of symptoms/radiological abnormalities at medium term follow up.

Methods: Prospective single centre observational study.

Results: Convalescent KL-6 levels were available for 93 patients (male 63%, mean age 55.8 years) who attended an 12-week follow up appointment after being admitted to hospital with COVID-19. For 67 patients a baseline KL-6 result was available for comparison. There was no significant correlations between baseline KL-6 and the admission CXR severity score or clinical severity NEWS score. Furthermore, there was no significant difference in the baseline KL-6 level and an initial requirement for oxygen on admission or the severity of acute infection as measured at 28 days. There was no significant difference in the 12-week KL-6 level and the presence or absence of subjective breathlessness but patients with abnormal CT scans at 12 weeks had significantly higher convalescent KL-6 levels compared to the remainder of the cohort (median 1101 IU/ml vs 409 IU/ml).

Conclusions: The association between high KL-6 levels at 12 weeks and persisting CT abnormalities (GGO/fibrosis), is a finding that requires further exploration. Whether KL-6 may help differentiate those patients with persisting dyspnoea due to complications rather than deconditioning or dysfunctional breathing alone, is an important future research question.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • COVID-19 / blood*
  • COVID-19 / diagnostic imaging
  • COVID-19 / pathology
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mucin-1 / blood*
  • Prospective Studies
  • SARS-CoV-2 / isolation & purification
  • Severity of Illness Index
  • Tomography, X-Ray Computed


  • Biomarkers
  • MUC1 protein, human
  • Mucin-1

Grant support

Fujirebio Europe UK provided financial support for the KL-6 assays but did not have any role in the study design, data collection and analysis, decision to publish, author salaries or preparation of the manuscript. The DISCOVER study was supported by donations to Southmead Hospital Charity (Registered Charity Number 1055900).