The role of hyaluronan synthesis and degradation in the critical respiratory illness COVID-19.

Hyaluronan (HA) is a polysaccharide found in all tissues as an integral component of the extracellular matrix (ECM) that plays a central regulatory role in inflammation. In fact, HA matrices are increasingly considered as a barometer of inflammation. A number of proteins specifically recognize the HA structure and these interactions modify cell behavior and control the stability of the ECM. Moreover, inflamed airways are remarkably rich with HA and are associated with various inflammatory diseases including cystic fibrosis, influenza, sepsis, and more recently coronavirus disease 2019 (COVID-19). COVID-19 is a worldwide pandemic caused by a novel coronavirus called SARS-CoV-2, and infected individuals have a wide range of disease manifestations ranging from asymptomatic to severe illness. Critically ill COVID-19 patient cases are frequently complicated by development of acute respiratory distress syndrome (ARDS), which typically leads to poor outcomes with high mortality rate. In general, ARDS is characterized by poor oxygenation accompanied with severe lung inflammation, damage, and vascular leakage and has been suggested to be linked to an accumulation of HA within the airways. Here, we provide a succinct overview of known inflammatory mechanisms regulated by HA in general, and those both observed and postulated in critically ill patients with COVID-19.