Harnessing the power of extracellular matrix to treat COVID-19 ARDS

COVID-19是一种可能危及生命的感染，通过急性肺损伤及其更严重的成人呼吸窘迫综合征（ARDS）的发展导致呼吸衰竭。尽管正在进行许多研究以确定治疗COVID-19急性呼吸窘迫综合征的治疗方法，但迄今为止尚未取得突破。急性呼吸窘迫综合征会导致肺部明显的炎症和基质积累，而细胞外基质是一种已知的炎症调节剂。透明质酸（HA）是一种糖胺聚糖，是肺细胞外基质的丰富成分，是肺损伤、炎症和修复的有力调节剂。最近的报告表明，HA可能是COVID-19应对的重要媒介。特别是，HMW-HA具有抗病毒、抗炎和促肺修复的特性。我们已经表明，HMW-HA改善肺损伤后的一些感染性和毒性暴露。ha结合蛋白间抑制剂（II）是一种有效的蛋白酶抑制剂，可改善肺上皮和内皮损伤。因此，我们假设HMW-HA和II通过对肺上皮和内皮的抗病毒和促稳态作用有效治疗covid -19相关的ARDS。

COVID-19 is a potentially life-threatening infection leading to respiratory failure through the development of Acute Lung Injury and its more severe form Adult Respiratory Distress Syndrome (ARDS). Although many studies are underway to determine therapeutic approaches to treating COVID-19 ARDS, no breakthroughs have been achieved to date. ARDS leads to significant inflammation and matrix accumulation in the lung, and extracellular matrix is a known modulator of inflammation. Hyaluronan (HA) is a glycosaminoglycan sugar, abundant component of the lung extracellular matrix, and is a powerful modulator of lung injury, inflammation and repair. Recent reports suggest that HA may be a crucial mediator of the COVID-19 response. In particular, HMW-HA has both antiviral, anti-inflammatory and pro-lung repair properties. We have shown that HMW-HA ameliorates lung injury after a number of infectious and toxic exposures. The HA-binding protein inter--inhibitor (II) is a powerful protease inhibitor which ameliorates epithelial and endothelial injury in the lung. We therefore hypothesized that HMW-HA and II are effective treatments of COVID-19-associated ARDS through antiviral and pro-homeostatic actions on lung epithelia and endothelia. We have demonstrated that hyaluronan (HA) and inter-alpha-inhibitor (IaI) can inhibit SARS-CoV-2 entry into cells in several models. We are currently working out the mechanisms and expanding into animal models to identify whether this treatment can be applied in COVID-19-induced lung injury