Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Br J Pharmacol. 2021 Jul;178(14):2832-2848. doi: 10.1111/bph.15187. Epub 2020 Jul 27.
The complement system is an ancient part of innate immunity sensing highly pathogenic coronaviruses by mannan-binding lectin (MBL) resulting in lectin pathway activation and subsequent generation of the anaphylatoxins (ATs) C3a and C5a as important effector molecules. Complement deposition on endothelial cells and high blood C5a serum levels have been reported in COVID-19 patients with severe illness, suggesting vigorous complement activation leading to systemic thrombotic microangiopathy (TMA). Complement regulator gene variants prevalent in African-Americans have been associated with a higher risk for severe TMA and multi-organ injury. Strikingly, severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2)-infected African-Americans suffer from high mortality. These findings allow us to apply our knowledge from other complement-mediated diseases to COVID-19 infection to better understand severe disease pathogenesis. Here, we discuss the multiple aspects of complement activation, regulation, crosstalk with other parts of the immune system, and the options to target complement in COVID-19 patients to halt disease progression and death. LINKED ARTICLES: This article is part of a themed issue on Canonical and non-canonical functions of the complement system in health and disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.14/issuetoc.
补体系统是先天免疫的一个古老组成部分，它通过甘露聚糖结合凝集素（MBL）感应高致病性冠状病毒，导致凝集素途径激活，随后产生重要效应分子 C3a 和 C5a 过敏毒素。COVID-19 重症患者的内皮细胞上有补体沉积和血液中 C5a 血清水平升高，表明补体的强烈激活导致全身性血栓性微血管病（TMA）。在非裔美国人中普遍存在的补体调节基因变异与严重 TMA 和多器官损伤的风险增加有关。引人注目的是，感染严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的非裔美国人死亡率很高。这些发现使我们能够将从其他补体介导的疾病中获得的知识应用于 COVID-19 感染，以更好地了解严重疾病的发病机制。在这里，我们讨论补体激活、调节、与免疫系统其他部分的相互作用的多个方面，以及在 COVID-19 患者中靶向补体以阻止疾病进展和死亡的选择。相关文章：本文是关于补体系统在健康和疾病中的经典和非经典功能的专题的一部分。要查看本节中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.14/issuetoc/。
