Service Hospitalier Universitaire de Pneumologie Physiologie, CHU Grenoble-Alpes, La Tronche, France.
Service de Maladies Infectieuses et Tropicales, CHU Grenoble-Alpes, La Tronche, France.
Front Immunol. 2020 Jul 21;11:1714. doi: 10.3389/fimmu.2020.01714. eCollection 2020.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third coronavirus leading to a global health outbreak. Despite the high mortality rates from SARS-CoV-1 and Middle-East respiratory syndrome (MERS)-CoV infections, which both sparked the interest of the scientific community, the underlying physiopathology of the SARS-CoV-2 infection, remains partially unclear. SARS-CoV-2 shares similar features with SARS-CoV-1, notably the use of the angiotensin conversion enzyme 2 (ACE2) as a receptor to enter the host cells. However, some features of the SARS-CoV-2 pandemic are unique. In this work, we focus on the association between obesity, metabolic syndrome, and type 2 diabetes on the one hand, and the severity of COVID-19 infection on the other, as it seems greater in these patients. We discuss how adipocyte dysfunction leads to a specific immune environment that predisposes obese patients to respiratory failure during COVID-19. We also hypothesize that an ACE2-cleaved protein, angiotensin 1-7, has a beneficial action on immune deregulation and that its low expression during the SARS-CoV-2 infection could explain the severity of infection. This introduces angiotensin 1-7 as a potential candidate of interest in therapeutic research on CoV infections.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）是导致全球卫生疫情的第三种冠状病毒。尽管 SARS-CoV-1 和中东呼吸综合征（MERS）-CoV 感染的死亡率很高，这两种病毒都引起了科学界的兴趣，但 SARS-CoV-2 感染的潜在病理生理学仍部分不清楚。SARS-CoV-2 与 SARS-CoV-1 具有相似的特征，特别是使用血管紧张素转换酶 2（ACE2）作为进入宿主细胞的受体。然而，SARS-CoV-2 大流行的一些特征是独特的。在这项工作中，我们关注肥胖、代谢综合征和 2 型糖尿病一方面与 COVID-19 感染严重程度之间的关联，因为在这些患者中似乎更为严重。我们讨论了脂肪细胞功能障碍如何导致特定的免疫环境，使肥胖患者在 COVID-19 期间易发生呼吸衰竭。我们还假设，ACE2 切割的蛋白血管紧张素 1-7 对免疫失调有有益的作用，而其在 SARS-CoV-2 感染期间的低表达可能解释了感染的严重程度。这将血管紧张素 1-7 引入作为 CoV 感染治疗研究的潜在候选物。
