Increased KL-6 levels in moderate to severe COVID-19 infection

Maureen Cambier; Monique Henket; Anne Noelle Frix; Stéphanie Gofflot; Marie Thys; Sara Tomasetti; Anna Peired; Ingrid Struman; Anne-Françoise Rousseau; Benoît Misset; Gilles Darcis; Michel Moutschen; Renaud Louis; Makon-Sébastien Njock; Etienne Cavalier; Julien Guiot

doi:10.1371/journal.pone.0273107

Increased KL-6 levels in moderate to severe COVID-19 infection

PLoS One. 2022 Nov 28;17(11):e0273107. doi: 10.1371/journal.pone.0273107. eCollection 2022.

Authors

Maureen Cambier^{1

2}, Monique Henket¹, Anne Noelle Frix¹, Stéphanie Gofflot³, Marie Thys⁴, Sara Tomasetti⁵, Anna Peired⁶, Ingrid Struman², Anne-Françoise Rousseau⁷, Benoît Misset⁷, Gilles Darcis⁸, Michel Moutschen^{8

9}, Renaud Louis^{1

10}, Makon-Sébastien Njock^{1

10}, Etienne Cavalier¹¹, Julien Guiot^{1

10}

Affiliations

¹ Department of Pneumology, University Hospital of Liège, Liège, Belgium.
² Laboratory of Molecular Angiogenesis, GIGA Research Center, University of Liège, Liège, Belgium.
³ Biothèque Hospitalo-Universitaire de Liège, University Hospital of Liège, Liège, Belgium.
⁴ Department of Biostatistics and Medico-Economic Information, University Hospital of Liège, Liège, Belgium.
⁵ Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy.
⁶ Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
⁷ Department of Intensive Care, University Hospital of Liège, Liège, Belgium.
⁸ Department of Infectious Diseases and General Internal Medicine, Liège University Hospital, Liège, Belgium.
⁹ AIDS Reference Laboratory, Liège University, Liège, Belgium.
¹⁰ Fibropole Research Group, GIGA Research Center, University of Liège, University Hospital of Liège, Liège, Belgium.
¹¹ Department of Clinical Chemistry, University of Liège, University Hospital of Liège, Liège, Belgium.

Abstract

Background: The global coronavirus disease 2019 (COVID-19) has presented significant challenges and created concerns worldwide. Besides, patients who have experienced a SARS-CoV-2 infection could present post-viral complications that can ultimately lead to pulmonary fibrosis. Serum levels of Krebs von den Lungen 6 (KL-6), high molecular weight human MUC1 mucin, are increased in the most patients with various interstitial lung damage. Since its production is raised during epithelial damages, KL-6 could be a helpful non-invasive marker to monitor COVID-19 infection and predict post-infection sequelae.

Methods: We retrospectively evaluated KL-6 levels of 222 COVID-19 infected patients and 70 healthy control. Serum KL-6, fibrinogen, lactate dehydrogenase (LDH), platelet-lymphocytes ratio (PLR) levels and other biological parameters were analyzed. This retrospective study also characterized the relationships between serum KL-6 levels and pulmonary function variables.

Results: Our results showed that serum KL-6 levels in COVID-19 patients were increased compared to healthy subjects (470 U/ml vs 254 U/ml, P <0.00001). ROC curve analysis enabled us to identify that KL-6 > 453.5 U/ml was associated with COVID-19 (AUC = 0.8415, P < 0.0001). KL-6 level was positively correlated with other indicators of disease severity such as fibrinogen level (r = 0.1475, P = 0.0287), LDH level (r = 0,31, P = 0,004) and PLR level (r = 0.23, P = 0.0005). However, KL-6 levels were not correlated with pulmonary function tests (r = 0.04, P = 0.69).

Conclusions: KL-6 expression was correlated with several disease severity indicators. However, the association between mortality and long-term follow-up outcomes needs further investigation. More extensive trials are required to prove that KL-6 could be a marker of disease severity in COVID-19 infection.

Copyright: © 2022 Cambier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Fibrinogen
Humans
Immunologic Tests
Retrospective Studies
SARS-CoV-2

Substances

Fibrinogen
MUC1 protein, human

Grants and funding

This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 101005122. The JU receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA. Authors initials who received funding for this work: MC, JG, ST, AP. This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 101005122. The JU receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA. Authors initials who received funding for this work: MC, JG, ST, AP. This study was partly supported by the European Union’s Horizon 2020 research and innovation programme (ICOVID, 101016131). Author initials who received funding for this work: JG. This work received support from the Leon Fredericq Fundation. Author initials who received funding for this work: JG. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study. This publication reflects the authors’ views; neither IMI, the European Union, EFPIA, nor the DRAGON and icovid Consortia are responsible for any use that may be made of the information contained herein.