Abstract
After millions of deaths, COVID-19 caused by SARS-CoV-2 has often been attributed to acute respiratory distress syndrome (ARDS). While COVID-19 ARDS has an acute clinical course, some patients experience non-resolvable (NR)-COVID-19 with fibroproliferation, inflammation, and vascular dysfunction. Hyaluronan (HA) has been implicated in multiple disease processes including ARDS, COVID-19, and pulmonary hypertension (PH). HA is synthesized by hyaluronidases (HAS) and its cleared by CD44. We hypothesized that HA levels were elevated in COVID-19 ARDS and persisted in NR-COVID-19.We utilized two distinct models of infection: exposure of mouse-adapted SARS-CoV-2 virus strain (MA10) and human angiotensin converting enzyme 2 (hACE2) transgenic mice exposed to the Washington SARS-CoV-2 strain (WA1). Lung tissue samples from COVID-19 ARDS patients, NR-COVID-19, and discarded donor lungs for transplantation were utilized for immunohistochemistry (IHC), RT-qPCR, and Western blots. Our experimental models of infection revealed increased mHas1 and mHas2 expression in MA10 infected mice. This was consistent with increased perivascular and parenchymal signals for HA following MA10 infection which was also seen in the hACE2 model. Human tissues revealed an increase in perivascular HA levels in COVID-19 ARDS and in NR COVID-19. Intriguingly, no significant differences in hHAS1-2 expression were detected, however transcript and protein levels of CD44 were reduced in NR-COVID-19, hinting at disrupted HA clearance. Taken together our data demonstrates that SARS-CoV-2 infection leads to increased HA levels that persist in NR-COVID-19 and may contribute to lung fibrosis and vascular injury.
Footnotes
Cite this article as ERJ Open Research 2022; 8: Suppl. 8, 175.
This article was presented at the 2022 ERS Lung Science Conference, in session “Poster Session 2”.
This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2022