Noureddine Rachid, Haddaji Asmaa, Baba Hanâ, Ouladlahsen Ahd, Aqillouch Safaa, Laazaazia Oumaima, Aainouss Achraf, Dehbi Hind, Ezzikouri Sayeh
Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco.
Laboratory of Genetics and Molecular Pathology, Medical School, University Hassan II, Casablanca, Morocco.
Int J Immunogenet. 2025 Aug;52(4):213-221. doi: 10.1111/iji.70002. Epub 2025 Jun 7.
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has significantly impacted global health, with Morocco reporting over 1.2 million confirmed cases and more than 16,300 deaths. The severity of COVID-19 varies, ranging from asymptomatic cases to mild symptoms, acute respiratory failure and death. Genetic factors are believed to influence individual responses to the virus. This study investigates the association between two common single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs)-TLR2 rs3804099 (+597 C/T) and TLR4 rs4986790 (+896 A/G)-and disease severity and inflammatory markers in Moroccan COVID-19 patients. A total of 452 COVID-19 patients (259 with mild/moderate disease and 193 with severe disease) were included. TLR2 and TLR4 SNPs were genotyped using a predesigned TaqMan real-time allelic discrimination assay. Complete blood count samples, along with levels of C-reactive protein (CRP), ferritin, procalcitonin and D-dimer, were assessed using automated methods. No significant associations were observed between either SNP in TLR2 and TLR4 and disease severity under various genetic models. However, in severe cases, TLR4 rs4986790 showed a significant association with ferritin levels (p = 0.0002) and lymphocyte count (p < 0.0001). TLR2 rs3804099 was linked to CRP levels in severe patients (p = 0.036). No associations were observed with anti-receptor-binding domain (RBD) IgG or anti-N IgG levels in severe cases (p > 0.05). These findings suggest that although TLR4 and TLR2 polymorphisms are not directly associated with COVID-19 severity, they may influence the inflammatory response. Specifically, TLR4 rs4986790 and TLR2 rs3804099 appear to modulate ferritin and CRP levels, potentially impacting disease progression in severe cases.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒引起的2019冠状病毒病疫情对全球健康产生了重大影响，摩洛哥报告了超过120万例确诊病例和16300多例死亡病例。2019冠状病毒病的严重程度各不相同，从无症状病例到轻微症状、急性呼吸衰竭和死亡。遗传因素被认为会影响个体对该病毒的反应。本研究调查了Toll样受体（TLR）中的两种常见单核苷酸多态性（SNP）——TLR2 rs3804099（+597 C/T）和TLR4 rs4986790（+896 A/G）——与摩洛哥2019冠状病毒病患者疾病严重程度和炎症标志物之间的关联。共纳入452例2019冠状病毒病患者（259例为轻/中度疾病患者，193例为重度疾病患者）。使用预先设计的TaqMan实时等位基因鉴别分析对TLR2和TLR4 SNPs进行基因分型。使用自动化方法评估全血细胞计数样本以及C反应蛋白（CRP）、铁蛋白、降钙素原和D-二聚体水平。在各种遗传模型下，未观察到TLR2和TLR4中的任何一种SNP与疾病严重程度之间存在显著关联。然而，在重症病例中，TLR4 rs4986790与铁蛋白水平（p = 0.0002）和淋巴细胞计数（p < 0.0001）显示出显著关联。TLR2 rs3804099与重症患者的CRP水平相关（p = 0.036）。在重症病例中，未观察到与抗受体结合域（RBD）IgG或抗N IgG水平存在关联（p > 0.05）。这些发现表明，尽管TLR4和TLR2多态性与2019冠状病毒病的严重程度没有直接关联，但它们可能会影响炎症反应。具体而言，TLR4 rs4986790和TLR2 rs3804099似乎会调节铁蛋白和CRP水平，可能会影响重症病例的疾病进展。
