COVID-19 AND THE RENIN ANGIOTENSIN SYSTEM: IMPLICATIONS FOR THE OLDER ADULTS
COVID-19 AND THE RENIN ANGIOTENSIN SYSTEM: IMPLICATIONS FOR THE OLDER ADULTS
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DOI：
10.1007/s12603-020-1403-7
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发表时间：
2020-06-04
影响因子：
5.8
通讯作者：
Bahat, G.
中科院分区：
文献类型：
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作者：
Bahat, G.
第700章 至少部分是通过增加血管通透性、血管张力和成纤维细胞活性以及减少肺泡上皮细胞存活来对肺损伤做出反应（8）。在许多肺部疾病中，Ang II 已被证明可介导疾病病理，例如特发性肺纤维化、胃酸或胎便误吸以及脓毒症 (5, 22-24)。与这一观点一致，据报道，ACE 抑制剂和血管紧张素 II 受体拮抗剂可以减轻实验性肺损伤 (8, 24)，并且据报道对实验动物模型和人类的一些肺炎病例有效 (25-27)。因此，血管紧张素转换酶抑制剂 (ACEIs)、血管紧张素受体阻滞剂 (ARB) 被认为可用于治疗弥漫性肺实质疾病和肺炎 (8, 25)。在导致缺氧的肺部疾病中，缺氧本身似乎会增加 Ang II 浓度 (28)。 ACE 受到缺氧诱导因子 1α 的启动子调节，缺氧诱导因子 1α 在缺氧条件下上调 ACE 表达，导致呼吸窘迫期间 Ang II 浓度增加。就 SARS-CoV-2 而言，由于 SARS-CoV-2 依赖 ACE2 蛋白进入并感染细胞，因此 RAS 进一步参与其中。此外，病毒本身也会下调 ACE2 的表达。因此，SARS-CoV-2 感染似乎比其他呼吸道感染更多地增加了针对 Ang (1-7) 的非拮抗 Ang II。由于 Covid-19 中更占主导地位的 Ang II 通路，这可能会导致更加夸张的症状。据报道，Covid-19 最常见的临床症状是发烧、疲劳、干咳、厌食、肌痛和呼吸困难 (29, 30)。有趣的是，嗅觉丧失和味觉障碍在一些报告中被认为是大流行期间的主要症状 (31, 32)。根据轶事报告后不断增加的观察结果，英国耳鼻喉科和鼻科学会建议将嗅觉丧失纳入症状标准，以触发隔离以限制 Covid-19 传播 (33)。这份报告指出，在韩国，30% 的检测呈阳性的患者在其他轻微病例中，有嗅觉丧失作为主要症状 (33)。在一项从 12 家欧洲医院招募的 417 名实验室确诊的轻中度 Covid-19 感染患者的研究中，约 85% 的患者普遍存在嗅觉和味觉功能障碍，并且嗅觉功能障碍与鼻漏或鼻塞无关 (34)。另一项研究重点关注来自美国的 262 名具有流感样症状的流动个体的嗅觉和味觉障碍，嗅觉和味觉障碍与阳性检测和区分 Covid-19 感染密切相关 (31)。这些症状约占 70%，几乎与发烧、咳嗽和肌痛一样常见 (31)。同样，在意大利连续 202 例在家管理的轻度症状确诊 Covid-19 病例中，嗅觉或味觉障碍高达 64.4%，其中 24% 为严重障碍（32）。其中只有约 1/3 的患者报告鼻塞 (32)。它们通常是第一个明显的症状，更常见于
700 at least in part, the response to lung injury through increase in vascular permeability, vascular tone and fibroblast activity, and by reducing alveolar epithelial cell survival (8). In a number of lung diseases Ang II has been shown to mediate the disease pathology eg idiopathic pulmonary fibrosis, acid or meconium aspiration and sepsis (5, 22-24). In line with this view, ACE inhibitors and angiotensin II receptor antagonists were reported to attenuate experimental lung injury (8, 24) and have been reported to be useful in some pneumonia cases of experimental animal models and in human (25-27). Accordingly, angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) were suggested to be useful in the treatment of diffuse parenchymal lung disease and pneumonia (8, 25). In lung diseases causing hypoxia, hypoxia itself seems to increase Ang II concentrations (28). ACE is under promoter regulation by hypoxia-inducing factor 1α that upregulates the ACE expression under hypoxic conditions, resulting in an increase in Ang II concentration during the respiratory distress. In the case of SARS-CoV-2, a further involvement of RAS occurs through the fact that SARS-CoV-2 relies on ACE2 protein to enter and infect the cell. Furthermore, the virus itself downregulates ACE2 expression. Therefore, SARS-CoV-2 infection seems to increase unopposed Ang II against Ang (1-7) much more than the other respiratory infections. This can result in the much more exaggerated signs due to the more dominant Ang II pathway in Covid-19.The most common presenting clinical symptoms of the Covid-19 are reported as fever, fatigue, dry cough, anorexia, myalgias and dyspnea (29, 30). Interestingly, loss of smell and taste disturbances have been noted as a presenting symptom in some reports in the course of pandemic (31, 32). In line with increasing observations following the anecdotal reports, British otorhinolaryngology and rhinological society suggested anosmia to be included to the symptom criteria to trigger isolation for limiting Covid-19 dissemination (33). In this report, it has been signified that in South Korea, 30% of patients testing positive have had anosmia as their major presenting symptom in otherwise mild cases (33). In a study including 417 patients with laboratory-confirmed mild-moderate Covid-19 infection recruited from 12 European hospitals, olfactory and gustatory dysfunctions were prevalent in about 85% of the patients and olfactory dysfunction was not associated with rhinorrhea or nasal obstruction (34). In another study focusing on smell and taste disturbances among 262 ambulatory individuals with influenza-like symptoms from US, smell and taste impairment was strongly associated with positive testing and discriminating the Covid-19 infection (31). These symptoms were about 70% being nearly as common as fever, cough and myalgia (31). Similarly, among 202 consecutive mildly symptomatic confirmed Covid-19 cases at home management from Italy, smell or taste disturbances were as high as 64.4% and disturbance was severe in 24%(32). Only about 1/3 of those patients reported blocked nose (32). They were often the first apparent symptom, more frequent in