Department of Hypertension and Diabetes, Medical University of Gdansk, Gdansk, Poland.
Guys Richard Dimbleby Department of Cancer Research, Kings College London, London, UK.
J Physiol Pharmacol. 2020 Apr;71(2). doi: 10.26402/jpp.2020.2.01. Epub 2020 Jul 2.
COVID-19, which is caused by the single-stranded RNA severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has introduced significant therapeutic dilemmas in several areas. One of these is concern regarding the use of renin-angiotensin system (RAS) inhibitors. Dysfunction of the RAS has been observed in COVID-19 patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs), are associated with improved or worse clinical outcomes, remains unclear. RAS inhibitors are currently widely used in the treatment of hypertension. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with co-morbidities such as hypertension, coronary heart disease, and diabetes mellitus, particularly in the elderly. Therefore, several recently published research papers have focused on the management of hypertension during the COVID-19 pandemic, as this co-morbidity was found to be the most common in patients with coronavirus infections. SARS-CoV-2 viral surface protein is known to attach angiotensin converting enzyme-2 (ACE-2) on the cell membrane to facilitate viral entry into the cytoplasm. While the SARS-CoV-2 viral load remains the highest in upper respiratory tract of COVID-19 patients, it has also been reported in multiple sites in COVID-19, and patients not infrequently require the Intensive Care Units (ICU) admission. However, despite the theoretical concerns of possible increased ACE2 expression by RAS blockade, there is no evidence that RAS inhibitors are harmful during COVID-19 infection, and indeed they have been shown to be beneficial in some animal studies. In this review we summarise the pathophysiology of the interaction between RAS, ACEIs/ARBs inhibitors and COVID-19, and conclude, on the basis of current data, that RAS blockade should be maintained during the current coronavirus pandemic.
由单链 RNA 严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）引起的 COVID-19 在多个领域带来了重大的治疗难题。其中一个问题是对肾素-血管紧张素系统（RAS）抑制剂的使用的关注。在 COVID-19 患者中观察到 RAS 功能障碍，但 RAS 抑制剂（如血管紧张素转换酶抑制剂（ACEIs）和血管紧张素 II 型 1 型受体阻滞剂（ARBs））是否与改善或恶化的临床结果相关仍不清楚。RAS 抑制剂目前广泛用于治疗高血压。新出现的数据表明，在患有高血压、冠心病和糖尿病等合并症的 COVID-19 患者中，RAS 抑制剂与更高的关联度和更高的死亡率相关，尤其是在老年人中。因此，最近发表的几篇研究论文都集中在 COVID-19 大流行期间的高血压管理上，因为这种合并症是冠状病毒感染患者中最常见的。SARS-CoV-2 病毒表面蛋白已知附着在细胞膜上的血管紧张素转换酶-2（ACE-2）上，以促进病毒进入细胞质。虽然 COVID-19 患者上呼吸道中的 SARS-CoV-2 病毒载量最高，但在 COVID-19 的多个部位也有报道，而且患者经常需要入住重症监护病房（ICU）。然而，尽管 RAS 阻断可能导致 ACE2 表达增加的理论担忧，但没有证据表明 RAS 抑制剂在 COVID-19 感染期间有害，实际上，一些动物研究表明它们是有益的。在这篇综述中，我们总结了 RAS、ACEIs/ARBs 抑制剂与 COVID-19 之间相互作用的病理生理学，并根据当前数据得出结论，在当前的冠状病毒大流行期间，应维持 RAS 阻断。
