Host genetics of pediatric SARS-CoV-2 COVID-19 and multisystem inflammatory syndrome in children.
Host genetics of pediatric SARS-CoV-2 COVID-19 and multisystem inflammatory syndrome in children.
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DOI：
10.1097/mop.0000000000001061
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发表时间：
2021-12-01
影响因子：
3.6
通讯作者：
Cron RQ
中科院分区：
文献类型：
--
作者：
Schulert GS;Blum SA;Cron RQ
本综述旨在描述儿童重症COVID-19肺炎和儿童多系统炎症综合征（MIS-C）感染后并发症的遗传关联。目前已经开展了多种遗传方法，主要针对成人，并推断到儿童，包括全基因组关联研究（GWAS）、全外显子组和全基因组测序（WES/WGS）以及靶基因分析。来自成人重症COVID-19患者的数据已确定基因组区域（人类白细胞抗原位点和3p21.31）是潜在的危险因素。通过GWAS和靶基因方法，与病毒进入细胞相关的基因（ABO血型位点、ACE2、TMPRS22）与COVID-19重症患者有关。在严重的COVID-19中，已经通过几种遗传方法确定了I型干扰素（如IFNAR2）和抗病毒基因（如TLR7）的关联。WES已注意到与几种免疫调节基因（如SOCS1）的关联。靶基因方法已经在患有严重COVID-19的儿童和成人以及患有misc的儿童中发现了穿孔素介导的细胞溶解途径基因的突变。通过各种遗传方法，在严重的COVID-19和misc患者中发现了几种遗传关联。从广义上讲，COVID-19的遗传关联包括与抗病毒功能、病毒进入细胞、免疫调节、白细胞趋化和淋巴细胞溶解功能相关的基因。
This review is meant to describe the genetic associations with pediatric severe COVID-19 pneumonia and the postinfectious complication of the multisystem inflammatory syndrome in children (MIS-C). Multiple genetic approaches have been carried out, primarily in adults with extrapolation to children, including genome-wide association studies (GWAS), whole exome and whole genome sequencing (WES/WGS), and target gene analyses. Data from adults with severe COVID-19 have identified genomic regions (human leukocyte antigen locus and 3p21.31) as potential risk factors. Genes related to viral entry into cells (ABO blood group locus, ACE2, TMPRS22) have been linked to severe COVID-19 patients by GWAS and target gene approaches. Type I interferon (e.g. IFNAR2) and antiviral gene (e.g. TLR7) associations have been identified by several genetic approaches in severe COVID-19. WES has noted associations with several immune regulatory genes (e.g. SOCS1). Target gene approaches have identified mutations in perforin-mediated cytolytic pathway genes in children and adults with severe COVID-19 and children with MIS-C. Several genetic associations have been identified in individuals with severe COVID-19 and MIS-C via various genetic approaches. Broadly speaking, COVID-19 genetic associations include genes involved with antiviral functions, viral cell entry, immune regulation, chemotaxis of white blood cells, and lymphocyte cytolytic function.