Hyaluronan is abundant in COVID-19 respiratory secretions

Kaber, G.; Kratochvil, M. J.; Burgener, E. B.; Peltan, E. L.; Barlow, G.; Yang, S.; Nicolls, M. R.; de Jesus Perez, V.; Rosser, J. I.; Wardle, A. J.; Kalinowski, A.; Ozawa, M. G.; Regula, D. P.; Nagy, N.; Heilshorn, S. C.; Milla, C. E.; Rogers, A. J.; Bollyky, P. L.

COVID-19 respiratory infections are associated with copious, adherent respiratory secretions that prolong chronic ventilation and contribute to the morbidity and mortality caused by the disease. We hypothesized that hyaluronan, an extracellular matrix glycosaminoglycan produced at sites of active inflammation that promotes edema in other settings, might be a component of these secretions. To interrogate this, we examined the respiratory secretions collected from eight intubated patients with COVID-19, six control patients with cystic fibrosis (CF), a different respiratory disease also associated with thick adherent secretions, and eight healthy controls. In this sample set we found that hyaluronan content is increased approximately 20-fold in both CF and COVID-19 patients compared to healthy controls. The hyaluronan in COVID-19 samples was comprised of low-molecular weight fragments, the hyaluronan form most strongly linked with pro-inflammatory functions. Hyaluronan is similarly abundant in histologic sections from cadaveric lung tissue from COVID-19 patients. These findings implicate hyaluronan in the thick respiratory secretions characteristic of COVID-19 infection. Therapeutic strategies targeting hyaluronan should be investigated further for potential use in patients with COVID-19.