Crespi Bernard
Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada.
Evol Med Public Health. 2020 Oct 14;2020(1):314-322. doi: 10.1093/emph/eoaa036. eCollection 2020.
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. : 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.
作者运用进化医学的概念和工具来理解新冠疫情。这场疫情代表了一种不匹配的冲突，其动态变化和病理表现显然由三个主要因素驱动：（i）蝙蝠免疫系统依赖低炎症反应但基于干扰素的防御具有高效性；（ii）病毒策略以不同方式靶向人类干扰素系统，导致大量无症状和症状前传播；（iii）由过度炎症和高凝表型引起的高死亡率，这代表了失调的权衡，即免疫诱导的附带损害变得全身性且严重。该框架可以解释死亡率与年龄（这涉及免疫生命史向更高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。从相关单核苷酸多态性的全表型关联分析可以看出，新冠死亡率的遗传风险因素与炎症和凝血有关；全表型关联研究还提供了证据，与之前的几项研究一致，表明钙通道阻滞剂氨氯地平介导了死亡风险。新冠病毒是一种从蝙蝠传播到人类的病毒。该病毒适应了蝙蝠免疫系统，在那里它进化以抑制哺乳动物用于告知自身被感染的免疫防御（干扰素）。在人类中，该病毒显然可以在体内有效传播，症状产生和免疫反应启动会延迟。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，从而对身体造成副作用性损害。老年人更容易感染该病毒，因为与年轻人相比，他们对新型感染因子的适应能力较差，且在免疫防御方面投入较少。增加新冠病毒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，这可能代表一种有效的治疗方法。
