KL-6 in ARDS and COVID-19 Patients

The Acute Respiratory Distress Syndrome (ARDS) is a common, devastating clinical pattern characterized by life-threatening respiratory failure. In ARDS there is an uncontrolled inflammatory response that results in alveolar damage, with the exudation of protein-rich pulmonary-edema fluid in the alveolar space. Although severe COVID-19 lung failure (CARDS) often meets diagnostic criteria of traditional ARDS, additional features have been reported, such as delayed onset, binary pulmonary compliant states, and hypercoagulable profile. Increased levels of Krebs von den Lungen 6 (KL-6, also known as MUC1) have been reported in both ARDS and CARDS. KL-6 is a transmembrane protein expressed on the apical membrane of most mucosal epithelial cells and it plays a critical role in lining the airway lumen. Abnormalities in mucus production contribute to severe pulmonary complications and death from respiratory failure in patients with diseases such as cystic fibrosis, chronic obstructive pulmonary disease, and acute lung injury due to viral pathogens. Nevertheless, it is not clear what role KL-6 plays in ARDS/CARDS pathophysiology. KL-6 may exert anti-inflammatory effects through the intracellular segment, as proven in animal models of ARDS, while its extracellular segment will enter the blood circulation through the alveolar space when the alveolar epithelial cells are damaged. Therefore, changes in plasma KL-6 levels may be useful in ARDS and CARDS phenotyping, and KL-6 might guide future clinical trials in ‘personalized medicine’ settings.