Combined use of serum KL-6 and respiratory functional parameters for identifying fibrotic lung damage in SARS-CoV-2-induced interstitial pneumonia

Combined use of serum KL-6 and respiratory functional parameters for identifying fibrotic lung damage in SARS-CoV-2-induced interstitial pneumonia

Authors

  • Miriana d'Alessandro Respiratory diseases Unit. Department of Medical Sciences, Surgery and Neurosciences. University of Siena, Siena, Italy
  • Irene Paggi Respiratory diseases Unit. Department of Medical Sciences, Surgery and Neurosciences. University of Siena, Siena, Italy
  • Giusy Montuori Respiratory diseases Unit. Department of Medical Sciences, Surgery and Neurosciences. University of Siena, Siena, Italy
  • Paolo Cameli Respiratory diseases Unit. Department of Medical Sciences, Surgery and Neurosciences. University of Siena, Siena, Italy
  • Sara Biancucci Respiratory diseases Unit. Department of Medical Sciences, Surgery and Neurosciences. University of Siena, Siena, Italy
  • Laura Bergantini Respiratory diseases Unit. Department of Medical Sciences, Surgery and Neurosciences. University of Siena, Siena, Italy
  • Elena Bargagli Respiratory diseases Unit. Department of Medical Sciences, Surgery and Neurosciences. University of Siena, Siena, Italy

Keywords:

KL-6, pulmonary fibrosis post-COVID19, Interstitial lung diseases

Abstract

Background: Post-COVID19 pulmonary fibrosis (PCPF) has been reported in a significant proportion of patients who survive the acute SARS-CoV-2 infection. Krebs von den Lungen-6 (KL-6) emerges as a marker of disease severity and progression in COVID-19-related lung involvement.

Methods: A total of 231 patients (median age (interquartile range, IQR), 65[57-74] years; 143 males) were enrolled in the study. Thirty-four had IPF, 56 sarcoidosis, 141 had been hospitalized for COVID-19. After hospital discharge (median (IQR), 7(5–17) months), a diagnosis of PCPF was made in 65/141 patients and 76/141 did not show fibrotic abnormalities. Serum KL‐6 concentrations were measured by KL‐6 reagent assay (AIA-CL300, Tosoh Biosciences).

Results: Most PC-nonPF patients (n=70, 92%) did not require invasive mechanical ventilation (IMV) during hospital stay, while 27 (41.5%) of PCPF patients did. KL-6 concentrations were strongly suggestive of lung fibrosis with a cutoff value of 467.8 U/mL (sensitivity 73% and specificity 66%). Model obtained though machine learning approach combined lung parameters and KL-6 values for clustering fibrotic and non-fibrotic patients with an acceptable accuracy. KL-6>765 U/mL and FVC%≤88 cluster for 67% of IPF patients, while KL-6 values ≤765U/mL and FVC >60% for 81% of PCPF patients.

Conclusion: KL-6 levels are not significantly elevated in patients undergoing IMV, indicating that IMV per se does not alter the values of this biomarker, thereby further supporting its reliability in detecting PCPF. Our study proposed a combination of KL-6 values and clinical data may lead to a further improvement in diagnostic accuracy for pulmonary fibrosis, idiopathic and secondary to COVID19.

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Published

27-03-2026

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Section

Original Articles: Laboratory Research

How to Cite

1.
d'Alessandro M, Paggi I, Montuori G, Cameli P, Biancucci S, Bergantini L, et al. Combined use of serum KL-6 and respiratory functional parameters for identifying fibrotic lung damage in SARS-CoV-2-induced interstitial pneumonia. Sarcoidosis Vasc Diffuse Lung Dis [Internet]. 2026 Mar. 27 [cited 2026 Apr. 17];43(1):18009. Available from: https://mail.mattioli1885journals.com/index.php/sarcoidosis/article/view/18009