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

Abstract

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.

Association of serum Krebs von den Lungen-6 and chest CT as potential prognostic factors in severe acute respiratory syndrome SARS-CoV-2: a preliminary experience

“…sought to investigate and characterize the associations between clinical, laboratory, and imaging characteristics of asymptomatic and pre-symptomatic patients with SARS-CoV-2, finding that serum KL-6 value was one of the best parameters to distinguish asymptomatic patients with COVID-19-related CT infiltrates from asymptomatic patients without CT changes [27]. Finally, in more recent work by Arnold DT et al, the authors found that patients with abnormal CT scans at 12 weeks had significantly higher KL-6 levels during recovery than the group with negative CT [28]. In agreement with the above-mentioned works, we also found a significant association between KL-6 elevation and the presence of radiological alterations.…”

Krebs von den Lungen 6 (KL-6) levels in COVID-19 ICU patients are associated with mortality

“…The use of biomarkers to predict disease severity has proven essential for resource allocation, particularly for respiratory support needs. In a previous study on a population of 67 COVID survivors [ 15 ], median KL-6 was 365 U/ml (IQR 233–493), and the authors concluded that “high KL-6 levels at 12 weeks with persisting CT abnormalities (GGO/fibrosis) is a finding that requires further exploration”. D’Alessandro et al [ 16 ], in 14 severe COVID patients, found very elevated serum KL-6 concentrations (median IQR , 1125; 495–2034).…”

PASCLex: A comprehensive post-acute sequelae of COVID-19 (PASC) symptom lexicon derived from electronic health record clinical notes

“…[2] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] Most early studies on PASC symptoms relied on patient survey data, manual chart review, and in person follow-up. [6] , [12] , [13] , [15] , [16] , [17] , [18] These studies were often limited by sample size and reporting biases. Longitudinal electronic health record (EHR) data serve as a rich data source for studying PASC symptoms.…”