Human genetic factors associated with susceptibility to SARS-CoV-2 infection and COVID-19 disease severity.
Human genetic factors associated with susceptibility to SARS-CoV-2 infection and COVID-19 disease severity.
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DOI：
10.1186/s40246-020-00290-4
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发表时间：
2020-10-22
期刊：
影响因子：
4.5
通讯作者：
Tsakris A
中科院分区：
文献类型：
--
作者：
Anastassopoulou C;Gkizarioti Z;Patrinos GP;Tsakris A
2019年12月，新型冠状病毒中国在湖北省武汉市出现，标志着世界与一个特殊的时钟同步，它正在统计感染病例和死亡人数，而不是小时和分钟。具有高度传染性的严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)确实造成了相当大的发病率和死亡率，并极大地改变了我们的日常生活。随着我们对已知感染我们物种的第七种冠状病毒的不断了解，它的一些特征不断地让我们感到惊讶。其中包括由此产生的冠状病毒病2019年(新冠肺炎)的广泛临床表现，从无症状或轻微症状的感染到严重肺炎、呼吸衰竭和死亡。现在来自患者群体的数据开始积累关于人类遗传因素的数据，这些因素可能有助于观察到多样化的疾病严重程度。因此，我们认为谨慎的做法是审查迄今已在文献中报告的特定人类基因变异与临床疾病严重程度或感染易感性之间的关联(截至2020年8月初撰写本文时，更新时间为9月中旬)。通过这项工作，我们希望(I)通过批判性地总结当前关于宿主遗传学潜在作用的知识来帮助快节奏的生物医学研究努力对抗病毒，以及(Ii)帮助指导当前的遗传学和基因组学研究，朝着值得在更大规模的研究中进一步研究的候选基因变体。我们发现，新冠肺炎严重程度不同的决定因素主要包括对病毒的免疫反应组件，而对SARS-CoV-2不同易感性的决定因素主要涉及与感染初期阶段相关的基因(即细胞表面受体的结合和进入)。阐明新冠肺炎严重程度和对SARS-CoV-2感染易感性的遗传决定因素将允许根据风险对个人进行分层，以便例如在开发出安全有效的疫苗时，优先接种高危人群。我们对潜在生物学机制的深入理解也可以指导个性化治疗。这些知识已经开始提供线索，至少在一定程度上有助于解释目前关于老年男性和儿童通常更严重或更良性疾病病程的流行病学观察。
The emergence of the novel coronavirus in Wuhan, Hubei Province, China, in December 2019 marked the synchronization of the world to a peculiar clock that is counting infected cases and deaths instead of hours and minutes. The pandemic, highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has indeed caused considerable morbidity and mortality and drastically changed our everyday lives. As we continue to become acquainted with the seventh coronavirus known to infect our species, a number of its characteristics keep surprising us. Among those is the wide spectrum of clinical manifestations of the resulting coronavirus disease 2019 (COVID-19), which ranges from asymptomatic or mildly symptomatic infections to severe pneumonia, respiratory failure, and death. Data, now from patient populations, are beginning to accumulate on human genetic factors that may contribute to the observed diversified disease severity. Therefore, we deemed it prudent to review the associations between specific human genetic variants and clinical disease severity or susceptibility to infection that have been reported in the literature to date (at the time of writing this article in early August 2020 with updates in mid-September). With this work, we hope (i) to assist the fast-paced biomedical research efforts to combat the virus by critically summarizing current knowledge on the potential role of host genetics, and (ii) to help guide current genetics and genomics research towards candidate gene variants that warrant further investigation in larger studies. We found that determinants of differing severity of COVID-19 predominantly include components of the immune response to the virus, while determinants of differing susceptibility to SARS-CoV-2 mostly entail genes related to the initial stages of infection (i.e., binding of the cell surface receptor and entry). Elucidating the genetic determinants of COVID-19 severity and susceptibility to SARS-CoV-2 infection would allow for the stratification of individuals according to risk so that those at high risk would be prioritized for immunization, for example, if or when safe and effective vaccines are developed. Our enhanced understanding of the underlying biological mechanisms could also guide personalized therapeutics. Such knowledge is already beginning to provide clues that help explain, at least in part, current epidemiologic observations regarding the typically more severe or benign disease course in older males and children, respectively.
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