Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome
Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome
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DOI：
10.7554/elife.57555
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发表时间：
2020-04-27
期刊：
影响因子：
7.7
通讯作者：
van der Hoeven, Hans
中科院分区：
文献类型：
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作者：
van de Veerdonk, Frank L.;Netea, Mihai G.;van der Hoeven, Hans
COVID-19患者在疾病早期可出现肺水肿。我们认为这是由于肺内皮细胞上的缓激肽1受体（B1R）和B2R的激活引起的局部血管问题。SARS-CoV-2通过ACE2进入细胞，它在RAAS中的作用是灭活des-Arg9缓激肽，这是B1R的有效配体。没有ACE2作为监护人使B1R配体失活，肺环境容易发生局部血管渗漏导致血管性水肿。在这里，我们假设通过B1R和最终B2R发生的kinin依赖性局部肺血管性水肿是COVID-19的一个重要特征。我们认为，阻断B2R和抑制血浆钾激肽活性可能对COVID-19引起的早期疾病有改善作用，并可能预防急性呼吸窘迫综合征（ARDS）。此外，这一途径可能间接对抗炎药物有反应。
COVID-19 patients can present with pulmonary edema early in disease. We propose that this is due to a local vascular problem because of activation of bradykinin 1 receptor (B1R) and B2R on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2 that next to its role in RAAS is needed to inactivate des-Arg9 bradykinin, the potent ligand of the B1R. Without ACE2 acting as a guardian to inactivate the ligands of B1R, the lung environment is prone for local vascular leakage leading to angioedema. Here, we hypothesize that a kinin-dependent local lung angioedema via B1R and eventually B2R is an important feature of COVID-19. We propose that blocking the B2R and inhibiting plasma kallikrein activity might have an ameliorating effect on early disease caused by COVID-19 and might prevent acute respiratory distress syndrome (ARDS). In addition, this pathway might indirectly be responsive to anti-inflammatory agents.