Genetic gateways to COVID-19 infection: Implications for risk, severity, and outcomes
Genetic gateways to COVID-19 infection: Implications for risk, severity, and outcomes
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COVID-19 感染的遗传途径：对风险、严重程度和结果的影响
DOI：
10.1096/fj.202001115r
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发表时间：
2020-06-11
期刊：
影响因子：
4.8
通讯作者：
Berk, Michael
中科院分区：
文献类型：
--
作者：
Debnath, Monojit;Banerjee, Moinak;Berk, Michael
2019年冠状病毒病（COVID-19）的传播、空间流行病学和临床过程等动态已成为最有趣的特征，但仍不完全清楚。特别是个体的遗传景观，以及总体上的群体似乎在塑造上述COVID-19动态方面发挥了关键作用。考虑到宿主基因在SARS-CoV-2进入和复制以及启动宿主免疫应答中的意义，似乎多个基因可能在上述过程中起关键作用。在此，我们提出了COVID-19感染的三个潜在的重要遗传途径;这些至少可以部分解释其传播，严重程度和死亡率的差异。血管紧张素转换酶2（ACE 2）基因内的变异可能构成第一个遗传门户，影响COVID-19的空间传播动力学。人类白细胞抗原基因座是抗感染免疫力的主要调节因子，似乎在影响COVID-19的易感性和严重性方面至关重要，可能是第二个遗传门户。调节Toll样受体和补体途径以及随后的细胞因子风暴诱导的过度炎症途径的基因似乎是COVID-19严重程度的基础，这些基因可能代表第三个遗传途径。宿主-病原体相互作用是一个复杂的事件，一些额外的基因也可能有助于COVID-19的动态。总的来说，本文提出的这三个遗传网关可能是决定COVID-19风险、严重程度和结果的关键宿主决定因素。这些关口内的遗传变异可能是影响COVID-19地理差异的关键。
The dynamics, such as transmission, spatial epidemiology, and clinical course of Coronavirus Disease-2019 (COVID-19) have emerged as the most intriguing features and remain incompletely understood. The genetic landscape of an individual in particular, and a population in general seems to play a pivotal role in shaping the above COVID-19 dynamics. Considering the implications of host genes in the entry and replication of SARS-CoV-2 and in mounting the host immune response, it appears that multiple genes might be crucially involved in the above processes. Herein, we propose three potentially important genetic gateways to COVID-19 infection; these could explain at least in part the discrepancies of its spread, severity, and mortality. The variations within Angiotensin-converting enzyme 2 (ACE2) gene might constitute the first genetic gateway, influencing the spatial transmission dynamics of COVID-19. The Human Leukocyte Antigen locus, a master regulator of immunity against infection seems to be crucial in influencing susceptibility and severity of COVID-19 and can be the second genetic gateway. The genes regulating Toll-like receptor and complement pathways and subsequently cytokine storm induced exaggerated inflammatory pathways seem to underlie the severity of COVID-19, and such genes might represent the third genetic gateway. Host-pathogen interaction is a complex event and some additional genes might also contribute to the dynamics of COVID-19. Overall, these three genetic gateways proposed here might be the critical host determinants governing the risk, severity, and outcome of COVID-19. Genetic variations within these gateways could be key in influencing geographical discrepancies of COVID-19.