Exploratory Science Center, MRL, Merck & Co., Inc, Cambridge, MA, USA.
MRL, Merck & Co., Inc, Boston, MA, USA.
Biochem Pharmacol. 2022 Jan;195:114847. doi: 10.1016/j.bcp.2021.114847. Epub 2021 Nov 18.
The host response to SARS-CoV-2, the virus that causes COVID-19, is highly heterogeneous, ranging from mild/asymptomatic to severe. The moderate to severe forms of COVID-19 often require hospitalization, are associated with a high rate of mortality, and appear to be caused by an inappropriately exaggerated inflammatory response to the virus. Emerging data confirm the involvement of both innate and adaptive immune pathways both in protection from SARS-CoV-2, and in driving the pathology of severe COVID-19. In particular, innate immune cells including neutrophils appear to be key players in the inflammation that causes the vicious cycle of damage and inflammation that underlies the symptomatology of severe COVID-19. Several recent studies support a link between damage and inflammation, with damage-associated molecular patterns (DAMPs) playing a key role in the pathology of severe COVID-19. In this review, we put into perspective the role of DAMPs and of components of the DAMP-signaling cascade, including Siglecs and their cognate ligands CD24 and CD52, in COVID-19. Further, we review clinical data on proposed therapeutics targeting DAMP pathways to treat SARS-CoV-2 infection and the regulation of these signaling cascades in COVID-19. We also discuss the potential impact of DAMP-mediated inflammation in other indications related to COVID-19, such as ARDS, endothelial dysfunction, hypercoagulation, and sepsis.
宿主对导致 COVID-19 的 SARS-CoV-2 病毒的反应高度异质，从轻症/无症状到重症不等。COVID-19 的中度至重度形式通常需要住院治疗，与高死亡率相关，似乎是由对病毒的不适当夸大的炎症反应引起的。新出现的数据证实，固有和适应性免疫途径都参与了对 SARS-CoV-2 的保护，以及驱动严重 COVID-19 的病理学。特别是，包括中性粒细胞在内的固有免疫细胞似乎是导致严重 COVID-19 症状的恶性循环中炎症的关键因素。最近的几项研究支持损伤和炎症之间存在联系，损伤相关分子模式（DAMPs）在严重 COVID-19 的病理学中发挥关键作用。在这篇综述中，我们从 DAMPs 及其 DAMP 信号级联的组成部分的角度来看待它们的作用，包括 Siglecs 及其同源配体 CD24 和 CD52，在 COVID-19 中的作用。此外，我们还回顾了针对 DAMPs 途径的治疗 COVID-19 的感染和这些信号级联在 COVID-19 中的调节的临床数据。我们还讨论了 DAMPs 介导的炎症在与 COVID-19 相关的其他适应症中的潜在影响，例如 ARDS、内皮功能障碍、高凝和败血症。
