Elgedawy Gamalat A, Elabd Naglaa S, Salem Radwa H, Awad Samah M, Amer Amany A, Torayah Mohammad M, El-Koa Amal A, Abozeid Mai, Montaser Belal A, Aboshabaan Hind S, Abdelkreem Mervat, Helal Marwa L
Department of Clinical Biochemistry and Molecular Diagnostics, National Liver Institute, Menoufia University, Shebin El-Kom, Menoufia, Egypt.
Faculty of Medicine, Department of Tropical Medicine, Menoufia University, Shebin El-Kom, Menoufia, 32511, Egypt.
Infection. 2024 Dec;52(6):2213-2229. doi: 10.1007/s15010-024-02266-1. Epub 2024 May 4.
A wide range of clinical manifestations and outcomes, including liver injury, have been reported in COVID-19 patients. We investigated the association of three substantial gene polymorphisms (FURIN, IFNL4, and TLR2) with COVID-19 disease susceptibility and severity to help predict prognosis.
150 adult COVID-19-assured cases were categorized as follows: 78 patients with a non-severe presentation, 39 patients with severe disease, and 33 critically ill patients. In addition, 74 healthy controls were included. Clinical and laboratory evaluations were carried out, including complete and differential blood counts, D-dimer, lactate dehydrogenase (LDH), C-reactive protein (CRP), procalcitonin, ferritin, interleukin-6 (Il-6), and liver and kidney functions. FURIN (rs6226), IFNL4 (rs12979860), and TLR2 (rs3804099) genotyping allelic discrimination assays were conducted using real-time PCR.
The FURIN, IFNL4, and TLR2 genotypes and their alleles differed significantly between COVID-19 patients and controls, as well as between patients with severe or critical illness and those with a non-severe presentation. According to a multivariable regression analysis, FURIN (C/T + T/T) and TLR2 (T/C + C/C) mutants were associated with COVID-19 susceptibility, with odds ratios of 3.293 and 2.839, respectively. FURIN C/C and IFNL4 T/T mutants were significantly linked to severe and critical illnesses. Multivariate regression analysis showed that FURIN (G/C + C/C) genotypes and IFNL4 T/T homozygosity were independent risk factors associated with increased mortality.
FURIN, IFNL4, and TLR2 gene variants are associated with the risk of COVID-19 occurrence as well as increased severity and poor outcomes in Egyptian patients.
新冠病毒病（COVID-19）患者已报告有广泛的临床表现和结局，包括肝损伤。我们研究了三种重要基因多态性（弗林蛋白酶（FURIN）、干扰素λ4（IFNL4）和Toll样受体2（TLR2））与COVID-19易感性及严重程度的关联，以帮助预测预后。
150例确诊为COVID-19的成年患者分类如下：78例非重症患者、39例重症患者和33例危重症患者。此外，纳入74名健康对照者。进行了临床和实验室评估，包括全血细胞计数及分类、D-二聚体、乳酸脱氢酶（LDH）、C反应蛋白（CRP）、降钙素原、铁蛋白、白细胞介素-6（Il-6）以及肝肾功能。采用实时聚合酶链反应进行FURIN（rs6226）、IFNL4（rs12979860）和TLR2（rs3804099）基因分型等位基因鉴别检测。
COVID-19患者与对照者之间，以及重症或危重症患者与非重症患者之间，FURIN、IFNL4和TLR2的基因型及其等位基因存在显著差异。根据多变量回归分析，FURIN（C/T + T/T）和TLR2（T/C + C/C）突变体与COVID-19易感性相关，比值比分别为3.293和2.839。FURIN C/C和IFNL4 T/T突变体与重症和危重症显著相关。多变量回归分析表明，FURIN（G/C + C/C）基因型和IFNL4 T/T纯合性是与死亡率增加相关的独立危险因素。
FURIN基因、IFNL4基因和TLR2基因变异与埃及患者发生COVID-19的风险以及病情加重和不良结局相关。
