Evolutionary medical insights into the SARS-CoV-2 pandemic.
Evolutionary medical insights into the SARS-CoV-2 pandemic.
复制标题
DOI：
10.1093/emph/eoaa036
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Crespi B
中科院分区：
文献类型：
--
作者：
Crespi B
作者运用进化医学的概念和工具来理解SARS-CoV-2大流行。这次大流行代表了一场不匹配的冲突，其动态和病理显然是由三个主要因素驱动的：(i)蝙蝠免疫系统依赖于低炎症但高效的干扰素防御；（ii）针对人类干扰素系统的病毒策略，导致大量无症状和症状前传播；（ii）由高炎症和高凝表型引起的高死亡率，这代表了失调的权衡，由此附带的免疫诱导损伤变得全身性和严重。这个框架可以解释死亡率与年龄（包括免疫生活史向更高的炎症和凝血以及适应性免疫降低的转变）和性别（因为男性比女性衰老得更快）之间的关联。通过对相关snp的全现象关联分析，可以显示COVID-19死亡率的遗传危险因素与炎症和凝血有关；全现象相关性研究也提供了证据，与之前的几项研究一致，钙通道阻断药物氨氯地平可以调节死亡风险。概要：SARS-CoV-2是一种跳入人类体内的蝙蝠病毒。这种病毒适应了蝙蝠的免疫系统，在那里它进化到抑制免疫防御（干扰素），哺乳动物用干扰素来识别它们被感染。在人类中，病毒显然可以在体内有效传播，延迟症状的产生和免疫反应的启动。当检测到病毒时，这种延迟可能会促进过度活跃的免疫反应，作为副作用损害身体。与年轻人相比，老年人更容易受到病毒的攻击，因为他们对新型传染病的适应能力较差，在免疫防御方面的投入也较少。增加SARS-CoV-2死亡风险的基因在功能上与一种名为氨氯地平的药物相关，氨氯地平可能是一种有用的治疗方法。
The author apply concepts and tools from evolutionary medicine to understanding the SARS-CoV-2 pandemic. The pandemic represents a mismatched conflict, with dynamics and pathology apparently driven by three main factors: (i) bat immune systems that rely on low inflammation but high efficacy of interferon-based defenses; (ii) viral tactics that differentially target the human interferon system, leading to substantial asymptomatic and pre-symptomatic transmission; and (ii) high mortality caused by hyper-inflammatory and hyper-coagulatory phenotypes, that represent dysregulated tradeoffs whereby collateral immune-induced damage becomes systemic and severe. This framework can explain the association of mortality with age (which involves immune life-history shifts towards higher inflammation and coagulation and reduced adaptive immunity), and sex (since males senesce faster than females). Genetic-risk factors for COVID-19 mortality can be shown, from a phenome-wide association analysis of the relevant SNPs, to be associated with inflammation and coagulation; the phenome-wide association study also provides evidence, consistent with several previous studies, that the calcium channel blocking drug amlodipine mediates risk of mortality. Lay Summary: SARS-CoV-2 is a bat virus that jumped into humans. The virus is adapted to bat immune systems, where it evolved to suppress the immune defenses (interferons) that mammals use to tell that they are infected. In humans, the virus can apparently spread effectively in the body with a delay in the production of symptoms and the initiation of immune responses. This delay may then promote overactive immune responses, when the virus is detected, that damage the body as a side effect. Older people are more vulnerable to the virus because they are less adapted to novel infectious agents, and invest less in immune defense, compared to younger people. Genes that increase risk of mortality from SARS-CoV-2 are functionally associated with a drug called amlodipine, which may represent a useful treatment.
登录
查看更多内容
病毒逃避干扰素的十种策略。
影响因子：
30.3
作者：
García-Sastre A
通讯作者：
García-Sastre A
影响因子：
16.8
作者：
Hoffmann HH;Schneider WM;Rice CM
通讯作者：
Rice CM
影响因子：
9.4
作者：
Dijkman, Ronald;Jebbink, Maarten F.;van der Hoek, Lia
通讯作者：
van der Hoek, Lia
DOI：
10.1098/rstb.2019.0296
发表时间：
2019-09-30
影响因子：
6.3
作者：
Guth, Sarah;Visher, Elisa;Brook, Cara E.
通讯作者：
Brook, Cara E.
影响因子：
7.7
作者：
Brook, Cara E.;Boots, Mike;van Leeuwen, Anieke
通讯作者：
van Leeuwen, Anieke