ABSTRACT

We previously made the hypothesis that STING contributes to COVID-19. The present review detail new arguments for over-activation of STING pathways in COVID-19, following the description of hyper-coagulability and Kawasaki-like diseases in children. Indeed, Kawasaki disease is induced by overreaction of innate cells following exposition to various viruses, including herpes viruses which trigger STING. It predisposes to diffuse vasculitis and aneurysms, whereas STING is over-expressed in arterial aneurisms. The redness at the inoculation site of bacillus Calmette-Guérin, a specific feature of Kawasaki disease, is reproduced by activation of the STING pathway, which is inhibited upstream by aspirin, intravenous immunoglobulins, and Vitamin-D. SARS-CoV2 binding to ACE2 can lead to excessive angiotensin II signaling, which activates the STING pathway in mice. Over-activation of the STING-pathway promotes hyper-coagulability through release of interferon-β and tissue factor by monocytes-macrophages. Aspirin and dipyridamole, besides their anti-platelet activity, also reduce tissue factor procoagulant activity, and aspirin inhibits the STING pathway upstream of STING. Aspirin and dipyridamole may be used, in combination with drugs blocking downstream the activation of the STING pathway, like inhibitors of IL-6R and JAK/STAT pathways. The risk of bleeding should be low as bleeding has not been reported in severe COVID-19 patients.

 抽象的

我们之前假设 STING 会导致 COVID-19。本综述根据儿童高凝状态和川崎样疾病的描述，详细介绍了 COVID-19 中 STING 通路过度激活的新论点。事实上，川崎病是由先天细胞在接触各种病毒（包括引发 STING 的疱疹病毒）后过度反应而诱发的。它容易引起弥漫性血管炎和动脉瘤，而 STING 在动脉瘤中过度表达。卡介苗接种部位发红是川崎病的一个特有特征，它是通过激活 STING 途径而重现的，该途径受到阿司匹林、静脉注射免疫球蛋白和维生素 D 的上游抑制。 SARS-CoV2 与 ACE2 结合可导致过度的血管紧张素 II 信号传导，从而激活小鼠的 STING 通路。 STING 通路的过度激活通过单核细胞-巨噬细胞释放干扰素-β 和组织因子来促进高凝血性。阿司匹林和双嘧达莫除了具有抗血小板活性外，还降低组织因子促凝血活性，并且阿司匹林抑制STING通路上游的STING通路。阿司匹林和双嘧达莫可与阻断 STING 通路下游激活的药物（如 IL-6R 和 JAK/STAT 通路抑制剂）联合使用。由于尚未报告重症 COVID-19 患者出血，因此出血风险应该较低。