PDF(Pubmed)
Abstract：
COVID-19 is characterized by a heterogeneous clinical presentation and prognosis. Risk factors contributing to the development of severe disease include old age and the presence of comorbidities. However, the genetic background of the host has also been recognized as an important determinant of disease prognosis. Considering the pivotal role of innate immunity in the control of SARS-CoV-2 infection, we analyzed the possible contribution of several innate immune gene polymorphisms (including TLR2-rs5743708, TLR4-rs4986790, TLR4-rs4986791, CD14-rs2569190, CARD8-rs1834481, IL18-rs2043211, and CD40-rs1883832) in disease severity and prognosis. A total of 249 individuals were enrolled and further divided into five (5) groups, according to the clinical progression scale provided by the World Health Organization (WHO) (asymptomatic, mild, moderate, severe, and critical). We identified that elderly patients with obesity and/or diabetes mellitus were more susceptible to developing pneumonia and respiratory distress syndrome after SARS-CoV-2 infection, while the IL18-rs1834481 polymorphism was an independent risk factor for developing pneumonia. Moreover, individuals carrying either the TLR2-rs5743708 or the TLR4-rs4986791 polymorphisms exhibited a 3.6- and 2.5-fold increased probability for developing pneumonia and a more severe disease, respectively. Our data support the notion that the host\'s genetic background can significantly affect COVID-19 clinical phenotype, also suggesting that the IL18-rs1834481, TLR2-rs5743708, and TLR4-rs4986791 polymorphisms may be used as molecular predictors of COVID-19 clinical phenotype.
摘要：
COVID-19的特征是临床表现和预后不均。导致严重疾病发展的危险因素包括老年和合并症的存在。然而,宿主的遗传背景也被认为是疾病预后的重要决定因素。考虑到先天免疫在控制SARS-CoV-2感染中的关键作用，我们分析了几种先天免疫基因多态性(包括TLR2-rs5743708,TLR4-rs4986790,TLR4-rs4986791,CD14-rs2569190,CARD8-rs1834481,IL18-rs2043211和CD40-rs1883832)在疾病严重程度和预后中的可能作用.共纳入249人，并进一步分为五（5）组，根据世界卫生组织（WHO）提供的临床进展量表（无症状，温和,中度,严重,和关键)。我们发现，患有肥胖和/或糖尿病的老年患者在SARS-CoV-2感染后更容易发生肺炎和呼吸窘迫综合征，而IL18-rs1834481多态性是发生肺炎的独立危险因素.此外，携带TLR2-rs5743708或TLR4-rs4986791多态性的个体出现肺炎和更严重疾病的概率增加了3.6倍和2.5倍。分别。我们的数据支持这样的观点，即宿主的遗传背景可以显著影响COVID-19临床表型，还表明IL18-rs1834481、TLR2-rs5743708和TLR4-rs4986791多态性可用作COVID-19临床表型的分子预测因子。
