Koltzov Institute of Developmental Biology RAS, ul. Vavilova, 26, 119334 Moscow, Russia.
Int J Mol Sci. 2024 Oct 19;25(20):11267. doi: 10.3390/ijms252011267.
Discovered in late 2019, the SARS-CoV-2 coronavirus has caused the largest pandemic of the 21st century, claiming more than seven million lives. In most cases, the COVID-19 disease caused by the SARS-CoV-2 virus is relatively mild and affects only the upper respiratory tract; it most often manifests itself with fever, chills, cough, and sore throat, but also has less-common mild symptoms. In most cases, patients do not require hospitalization, and fully recover. However, in some cases, infection with the SARS-CoV-2 virus leads to the development of a severe form of COVID-19, which is characterized by the development of life-threatening complications affecting not only the lungs, but also other organs and systems. In particular, various forms of thrombotic complications are common among patients with a severe form of COVID-19. The mechanisms for the development of thrombotic complications in COVID-19 remain unclear. Accumulated data indicate that the pathogenesis of severe COVID-19 is based on disruptions in the functioning of various innate immune systems. The key role in the primary response to a viral infection is assigned to two systems. These are the pattern recognition receptors, primarily members of the toll-like receptor (TLR) family, and the complement system. Both systems are the first to engage in the fight against the virus and launch a whole range of mechanisms aimed at its rapid elimination. Normally, their joint activity leads to the destruction of the pathogen and recovery. However, disruptions in the functioning of these innate immune systems in COVID-19 can cause the development of an excessive inflammatory response that is dangerous for the body. In turn, excessive inflammation entails activation of and damage to the vascular endothelium, as well as the development of the hypercoagulable state observed in patients seriously ill with COVID-19. Activation of the endothelium and hypercoagulation lead to the development of thrombosis and, as a result, damage to organs and tissues. Immune-mediated thrombotic complications are termed "immunothrombosis". In this review, we discuss in detail the features of immunothrombosis associated with SARS-CoV-2 infection and its potential underlying mechanisms.
2019 年末发现的严重急性呼吸综合征冠状病毒 2 型（SARS-CoV-2）引发了 21 世纪最大的一次大流行，造成超过 700 万人死亡。在大多数情况下，由 SARS-CoV-2 病毒引起的 COVID-19 疾病相对较轻，仅影响上呼吸道；它最常表现为发热、寒战、咳嗽和喉咙痛，但也有不太常见的轻微症状。在大多数情况下，患者不需要住院，可完全康复。然而，在某些情况下，感染 SARS-CoV-2 病毒会导致 COVID-19 发展为严重形式，其特征是出现危及生命的并发症，不仅影响肺部，还影响其他器官和系统。特别是，严重 COVID-19 患者中常见各种形式的血栓并发症。COVID-19 中血栓并发症发展的机制尚不清楚。积累的数据表明，严重 COVID-19 的发病机制基于各种固有免疫系统功能障碍。两个系统被分配在对病毒感染的初步反应中起关键作用。这些系统是模式识别受体，主要是 Toll 样受体（TLR）家族成员，以及补体系统。这两个系统都首先参与对抗病毒，并启动一系列旨在快速消除病毒的机制。正常情况下，它们的联合活动会导致病原体的破坏和恢复。然而，COVID-19 中固有免疫系统功能障碍会导致过度炎症反应的发展，这对身体是危险的。反过来，过度炎症会导致血管内皮细胞的激活和损伤，以及严重 COVID-19 患者中观察到的高凝状态的发展。内皮细胞的激活和高凝会导致血栓形成，从而导致器官和组织受损。免疫介导的血栓并发症被称为“免疫血栓形成”。在这篇综述中，我们详细讨论了与 SARS-CoV-2 感染相关的免疫血栓形成的特征及其潜在的潜在机制。
