1 BACKGROUND

While this article was being written, the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) had infected over 4.48 million people in the United States, and killed over 152 000 of them (CDC COVID Data Tracker, 2020). The numbers for the rest of the world were not any better, with over 12.3 million people infected and nearly 510 000 killed by coronavirus disease 2019 (COVID‐19) (COVID‐19 Dashboard, 2020). Due to inconsistently applied public health practices and quarantines, an inadequate national response, and widely varying access to health care, the pandemic continues to spread in the US, raising serious concerns about SARS‐CoV‐2 possibly killing several hundreds of thousands of people by the time it runs its course.

Phylogenetically related to both SARS‐CoV (SARS) and Middle East Respiratory Syndrome Coronavirus (MERS) (Boni et al., 2020; Fani et al., 2020; Lu, Wang, & Gao, 2015; Sironi et al., 2020; Zhou, Chen, et al., 2020; Zhou, Yu, et al., 2020), SARS‐CoV‐2 is fairly new to humans. Considerable effort has been made to trace its genetic origins in nonhuman species (eg, bats, pangolins, civets) that serve as reservoirs for this and related viruses, and track its path of transmission to humans (Lan et al., 2020; Sironi et al., 2020; Zhou, Chen, et al., 2020; Zhou, Yu, et al., 2020). Regardless of the source of the zoonotic transmission, it is clear that SARS‐CoV‐2 evolved and adapted in another host before being transferred to humans (Andersen, Rambaut, Ian Lipkin, Holmes, & Garry, 2020). There is further speculation that, before being identified in late 2019, SARS‐CoV‐2 had been infecting humans for some time, possibly causing mild illness (Andersen et al., 2020; Sironi et al., 2020). Through the process of human transmission, this coronavirus (CoV) may have acquired some key mutations that ultimate led to the emergence of the current pandemic strain (Boni et al., 2020; Sironi et al., 2020). In fact, recent data suggest that, since emerging and spreading globally, SARS‐CoV‐2 has evolved into two major forms in Europe and Asia, with both appearing in US populations at frequencies associated with their geographic proximity to these source areas (Forster, Forster, Renfrew, & Forster, 2020).

Building on insights from studies of SARS and MERS, ongoing research has enlarged our understanding of the origin of SARS‐CoV‐2 and its greater virulence compared to other CoVs. At the same time, the global health crisis caused by its spread from populations based in Asia has led to questions about how to mitigate its impact from clinical and public health standpoints, particularly for individuals and communities who have disproportionately suffered from coronavirus infection. This short commentary explores the epidemiology and biology of SARS‐CoV‐2 before examining the host genetic factors that may lead to differential susceptibility to COVID‐19 and varying immunological responses to viral infection. It concludes by reflecting on the way that knowledge about these genetic risk factors and the mechanism of SARS‐CoV‐2 infection is now being used for vaccine development.

中文翻译：

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宿主遗传因素和SARS-CoV-2感染的易感性

1背景

在撰写本文时，新型冠状病毒严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在美国感染了448万人，并杀死了152 000多人（CDC COVID Data Tracker，2020年）。世界其他地区的数字并没有好转，2019年有超过1,230万人被冠状病毒病感染，近510 000人被杀死（COVID-19）（COVID-19 Dashboard，2020年）。由于公共卫生实践和检疫方法不一致，国家反应不足以及获得医疗保健的机会千差万别，该流行病继续在美国蔓延，引起人们对SARS-CoV-2的严重关注，可能导致数十万人丧生。它运行的时间。

与SARS-CoV（SARS）和中东呼吸系统综合症冠状病毒（MERS）在系统发育上相关（Boni等人，2020 ; Fani等人，2020 ; Lu，Wang，＆Gao，2015 ; Sironi等人，2020 ; Zhou，Chen等，2020 ; Zhou，Yu等，2020），SARS-CoV-2对人类来说是相当新的事物。已经做出了相当大的努力来追踪其遗传起源于非人类物种（例如蝙蝠，穿山甲，麝香）作为该病毒和相关病毒的贮藏库，并追踪其向人类的传播途径（Lan等，2020； Sironi等）。等人，2020 ; Zhou，Chen等，2020 ; Zhou，Yu等，2020）。无论人畜共患疾病的传播来源如何，很明显，SARS-CoV-2都是在另一宿主中进化并适应后才转移给人类的（Andersen，Rambaut，Ian Lipkin，Holmes和Garry，2020年）。进一步的推测是，SARS-CoV-2在2019年底被发现之前已经感染了人类一段时间，可能引起轻度疾病（Andersen等，2020 ; Sironi等，2020）。通过人类传播的过程，这种冠状病毒（CoV）可能已经获得了一些关键突变，这些突变最终导致了当前大流行毒株的出现（Boni等，2020； Sironi等，2020）。实际上，最近的数据表明，SARS-CoV-2自从在全球出现并传播以来，已经在欧洲和亚洲演变成两种主要形式，两种形式都以与它们与这些来源地区的地理邻近度相关的频率出现在美国人口中（Forster， Forster，Renfrew和Forster，2020年）。

基于对SARS和MERS研究的见解，正在进行的研究扩大了我们对SARS-CoV-2的起源及其比其他CoV更大的毒力的理解。同时，由于其从亚洲人群中扩散而引起的全球健康危机，引发了有关如何从临床和公共卫生角度减轻其影响的问题，特别是对于受到冠状病毒感染严重影响的个人和社区。这篇简短的评论先探讨了SARS-CoV-2的流行病学和生物学，然后研究了可能导致对COVID-19敏感性差异和对病毒感染的免疫反应不同的宿主遗传因素。