Genetic Variations in TLR2 and TLR4 Genes and Their Association With COVID-19 Severity and Inflammatory Markers in the Moroccan Population

Abstract

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.