Background

Susceptibility to severe viral infections was reported to be associated with genetic variants in immune response genes using case reports and GWAS studies. SARS-CoV-2 is an emergent viral disease that caused millions of COVID-19 cases all over the world. Around 15 % of cases are severe and some of them are accompanied by dysregulated immune system and cytokine storm. There is increasing evidence that severe manifestations of COVID-19 might be attributed to human genetic variants in genes related to immune deficiency and or inflammasome activation (cytokine storm).

Objective

Identify the candidate genes that are likely to aid in explaining severe COVID-19 and provide insights to understand the pathogenesis of severe COVID-19.

Methods

In this article, we systematically reviewed genes related to viral susceptibility that were reported in human genetic studies (Case-reports and GWAS) to understand the role of host viral interactions and to provide insights into the pathogenesis of severe COVID-19.

Results

We found 40 genes associated with viral susceptibility and 21 of them were associated with severe SARS-CoV disease and severe COVID-19. Some of those genes were implicated in TLR pathways, others in C-lectin pathways, and others were related to inflammasome activation (cytokine storm).

Conclusion

This compilation represents a list of candidate genes that are likely to aid in explaining severe COVID-19 which are worthy of inclusion in gene panels and during meta-analysis of different variants in host genetics studies of COVID-19. In addition, we provide several hypotheses for severe COVID-19 and possible therapeutic targets.

中文翻译：

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宿主遗传学在人类对严重病毒感染的易感性中的作用以及对严重 COVID-19 宿主遗传学的见解：系统评价。

背景

据报道，使用病例报告和 GWAS 研究，对严重病毒感染的易感性与免疫反应基因的遗传变异有关。SARS-CoV-2 是一种突发的病毒性疾病，在全世界引起了数百万例 COVID-19 病例。约15%的病例病情严重，部分病例伴有免疫系统失调和细胞因子风暴。越来越多的证据表明，COVID-19 的严重表现可能归因于与免疫缺陷和/或炎性体激活（细胞因子风暴）相关的人类基因变异。

客观的

确定可能有助于解释重症 COVID-19 的候选基因，并为理解重症 COVID-19 的发病机制提供见解。

方法

在本文中，我们系统地回顾了人类遗传学研究（病例报告和 GWAS）中报告的与病毒易感性相关的基因，以了解宿主病毒相互作用的作用，并提供对严重 COVID-19 发病机制的见解。

结果

我们发现了 40 个与病毒易感性相关的基因，其中 21 个与严重的 SARS-CoV 疾病和严重的 COVID-19 相关。其中一些基因与 TLR 通路有关，另一些与 C-凝集素通路有关，还有一些与炎性体激活（细胞因子风暴）有关。

结论

该汇编列出了可能有助于解释严重 COVID-19 的候选基因列表，这些基因值得包含在基因面板中以及在 COVID-19 宿主遗传学研究中对不同变体进行荟萃分析时。此外，我们还针对重症 COVID-19 和可能的治疗靶点提供了几种假设。