Neither the disease mechanism nor treatments for COVID-19 are currently known. Here, we present a novel molecular mechanism for COVID-19 that provides therapeutic intervention points that can be addressed with existing FDA-approved pharmaceuticals. The entry point for the virus is ACE2, which is a component of the counteracting hypotensive axis of RAS. Bradykinin is a potent part of the vasopressor system that induces hypotension and vasodilation and is degraded by ACE and enhanced by the angiotensin1-9 produced by ACE2. Here, we perform a new analysis on gene expression data from cells in bronchoalveolar lavage fluid (BALF) from COVID-19 patients that were used to sequence the virus. Comparison with BALF from controls identifies a critical imbalance in RAS represented by decreased expression of ACE in combination with increases in ACE2, renin, angiotensin, key RAS receptors, kinogen and many kallikrein enzymes that activate it, and both bradykinin receptors. This very atypical pattern of the RAS is predicted to elevate bradykinin levels in multiple tissues and systems that will likely cause increases in vascular dilation, vascular permeability and hypotension. These bradykinin-driven outcomes explain many of the symptoms being observed in COVID-19.

中文翻译：

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涉及 RAS 介导的缓激肽风暴的 COVID-19 机制模型和治疗干预措施

目前尚不清楚 COVID-19 的疾病机制和治疗方法。在这里，我们提出了一种针对 COVID-19 的新型分子机制，该机制提供了可以使用 FDA 批准的现有药物来解决的治疗干预点。该病毒的入口点是 ACE2，它是 RAS 对抗低血压轴的一个组成部分。缓激肽是血管升压系统的有效组成部分，可引起低血压和血管舒张，可被 ACE 降解，并被 ACE2 产生的血管紧张素 1-9 增强。在这里，我们对来自 COVID-19 患者的支气管肺泡灌洗液 (BALF) 中用于病毒测序的细胞的基因表达数据进行了新的分析。与对照组的 BALF 进行比较，发现 RAS 存在严重不平衡，表现为 ACE 表达减少，同时 ACE2、肾素、血管紧张素、关键 RAS 受体、激肽原和许多激活它的激肽释放酶以及两种缓激肽受体的增加。RAS 的这种非常非典型的模式预计会提高多个组织和系统中的缓激肽水平，这可能会导致血管扩张、血管通透性和低血压增加。这些缓激肽驱动的结果解释了在 COVID-19 中观察到的许多症状。