Gressens Simon B, Leftheriotis Georges, Dussaule Jean-Claude, Flamant Martin, Levy Bernard I, Vidal-Petiot Emmanuelle
Department of Infectious and Tropical Diseases, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, France.
Laboratory of Molecular Physiology and Medicine, Université Cote d'Azur, Nice, France.
Front Physiol. 2021 Feb 22;12:624052. doi: 10.3389/fphys.2021.624052. eCollection 2021.
Since December 2019, the coronavirus 2019 (COVID-19) pandemic has rapidly spread and overwhelmed healthcare systems worldwide, urging physicians to understand how to manage this novel infection. Early in the pandemic, more severe forms of COVID-19 have been observed in patients with cardiovascular comorbidities, who are often treated with renin-angiotensin aldosterone system (RAAS)-blockers, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), but whether these are indeed independent risk factors is unknown. The cellular receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the membrane-bound angiotensin converting enzyme 2 (ACE2), as for SARS-CoV(-1). Experimental data suggest that expression of ACE2 may be increased by RAAS-blockers, raising concerns that these drugs may facilitate viral cell entry. On the other hand, ACE2 is a key counter-regulator of the RAAS, by degrading angiotensin II into angiotensin (1-7), and may thereby mediate beneficial effects in COVID-19. These considerations have raised concerns about the management of these drugs, and early comments shed vivid controversy among physicians. This review will describe the homeostatic balance between ACE-angiotensin II and ACE2-angiotensin (1-7) and summarize the pathophysiological rationale underlying the debated role of the RAAS and its modulators in the context of the pandemic. In addition, we will review available evidence investigating the impact of RAAS blockers on the course and prognosis of COVID-19 and discuss why retrospective observational studies should be interpreted with caution. These considerations highlight the importance of solid evidence-based data in order to guide physicians in the management of RAAS-interfering drugs in the general population as well as in patients with more or less severe forms of SARS-CoV-2 infection.
自2019年12月以来，2019冠状病毒病（COVID-19）大流行迅速蔓延，使全球医疗系统不堪重负，促使医生了解如何应对这种新型感染。在大流行早期，心血管合并症患者中观察到了更严重形式的COVID-19，这些患者常使用肾素-血管紧张素-醛固酮系统（RAAS）阻滞剂进行治疗，如血管紧张素转换酶抑制剂（ACEIs）或血管紧张素受体阻滞剂（ARBs），但这些是否确实是独立的危险因素尚不清楚。严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的细胞受体是膜结合的血管紧张素转换酶2（ACE2），与严重急性呼吸综合征冠状病毒（SARS-CoV(-1)）相同。实验数据表明，RAAS阻滞剂可能会增加ACE2的表达，这引发了人们对这些药物可能促进病毒进入细胞的担忧。另一方面，ACE2是RAAS的关键负调节因子，它将血管紧张素II降解为血管紧张素（1-7），从而可能在COVID-19中发挥有益作用。这些考虑引发了对这些药物管理的担忧，早期的观点在医生中引发了激烈的争议。本综述将描述ACE-血管紧张素II与ACE2-血管紧张素（1-7）之间的稳态平衡，并总结在大流行背景下RAAS及其调节剂作用争议背后的病理生理机制。此外，我们将回顾现有证据，研究RAAS阻滞剂对COVID-19病程和预后的影响，并讨论为何应谨慎解读回顾性观察性研究。这些考虑凸显了可靠的循证数据的重要性，以便指导医生在普通人群以及感染程度轻重不同的SARS-CoV-2患者中管理RAAS干扰药物。
