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

Arnold, David T.; Donald, Charmaine; Lyon, Max; Hamilton, Fergus W.; Morley, Anna J.; Attwood, Marie; Dipper, Alexandra; Barratt, Shaney L.

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.