McCoy Kendall, Peterson Autumn, Tian Yun, Sang Yongming
Department of Biology, College of Life and Physical Sciences, Tennessee State University, 3500 John A. Merritt Boulevard, Nashville, TN 37209, USA.
Department of Agricultural and Environmental Sciences, College of Agriculture, Tennessee State University, 3500 John A. Merritt Boulevard, Nashville, TN 37209, USA.
Vaccines (Basel). 2020 Nov 20;8(4):700. doi: 10.3390/vaccines8040700.
SARS-CoV2 has caused the current pandemic of new coronavirus disease 2019 (COVID-19) worldwide. Clinical outcomes of COVID-19 illness range broadly from asymptotic and mild to a life-threatening situation. This casts uncertainties for defining host determinants underlying the disease severity. Recent genetic analyses based on extensive clinical sample cohorts using genome-wide association studies (GWAS) and high throughput sequencing curation revealed genetic errors and gene loci associated with about 20% of life-threatening COVID-19 cases. Significantly, most of these critical genetic loci are enriched in two immune signaling pathways, i.e., interferon-mediated antiviral signaling and chemokine-mediated/inflammatory signaling. In line with these genetic profiling studies, the broad spectrum of COVID-19 illness could be explained by immuno-pathological regulation of these critical immunogenetic pathways through various epigenetic mechanisms, which further interconnect to other vital components such as those in the renin-angiotensin-aldosterone system (RAAS) because of its direct interaction with the virus causing COVID-19. Together, key genes unraveled by genetic profiling may provide targets for precisely early risk diagnosis and prophylactic design to relieve severe COVID-19. The confounding epigenetic mechanisms may be key to understanding the clinical broadness of COVID-19 illness.
严重急性呼吸综合征冠状病毒2（SARS-CoV2）已在全球引发了2019年新型冠状病毒病（COVID-19）的大流行。COVID-19疾病的临床结果差异很大，从无症状和轻症到危及生命的情况都有。这使得确定疾病严重程度背后的宿主决定因素存在不确定性。最近基于大量临床样本队列，利用全基因组关联研究（GWAS）和高通量测序筛选进行的基因分析，揭示了与约20%危及生命的COVID-19病例相关的基因错误和基因位点。值得注意的是，这些关键基因位点大多富集于两种免疫信号通路，即干扰素介导的抗病毒信号通路和趋化因子介导的/炎症信号通路。与这些基因谱研究一致，COVID-19疾病的广泛表现可以通过这些关键免疫遗传通路通过各种表观遗传机制进行的免疫病理调节来解释，由于其与导致COVID-19的病毒直接相互作用，这种调节还进一步与肾素-血管紧张素-醛固酮系统（RAAS）等其他重要成分相互关联。总之，基因谱分析揭示的关键基因可能为精确的早期风险诊断和预防性设计提供靶点，以缓解严重的COVID-19。混杂的表观遗传机制可能是理解COVID-19疾病临床广泛性的关键。
