Toll-Like Receptor 4 Polymorphisms (896A/G and 1196C/T) as an Indicator of COVID-19 Severity in a Convenience Sample of Egyptian Patients

• Published in: Journal of inflammation research 2021-01, Vol.14, p.6293-6303
• Main Authors: Taha, Sara I, Shata, Aalaa K, Baioumy, Shereen A, Fouad, Shaimaa H, Anis, Sherif G, Mossad, Isis M, Moustafa, Nouran M, Abdou, Dina M, Youssef, Mariam K
• Format: Article
• Language: English
• Subjects: Alleles; Coronaviruses; COVID-19; Cytokine storm; Diabetes; Disease; egypt; Enzyme-linked immunosorbent assay; Enzymes; Fatalities; Gene polymorphism; Genotype & phenotype; Hospitals; Immune response; Infections; Innate immunity; Interleukin 6; Laboratories; mortality; Original Research; Patients; Polymerase chain reaction; polymorphism; Restriction fragment length polymorphism; Serum levels; Severe acute respiratory syndrome coronavirus 2; severity; Single-nucleotide polymorphism; TLR4 protein; toll-like receptor; Toll-like receptors; Viral infections
• ISSN: 1178-7031; 1178-7031
• DOI: 10.2147/JIR.S343246

The clinical spectrum of COVID-19 is extremely variable. Thus, it is likely that the heterogeneity in the genetic make-up of the host may contribute to disease severity. Toll-like receptor (TLR)-4 plays a vital role in the innate immune response to SARS-CoV-2 infection. The susceptibility of humans to severe COVID-19 concerning TLR-4 single nucleotide polymorphisms (SNPs) has not been well examined. The goal of this research was to investigate the association between TLR-4 (Asp299Gly and Thr399Ile) SNPs and COVID-19 severity and progression as well as the cytokine storm in Egyptian patients. We genotyped 300 adult COVID-19 Egyptian patients for TLR-4 (Asp299Gly and Thr399Ile) SNPs using PCR-restriction fragment length polymorphism (PCR-RFLP). We also measured interleukin (IL)-6 levels by enzyme-linked immunosorbent assay (ELISA) as an indicator of the cytokine storm. The minor 299Gly (G) and 399Ile (T) alleles were associated with a significant (P < 0.001) positive risk of severe COVID-19 (OR = 3.14; 95% CI = 2.02-4.88 and OR = 2.75; 95% CI = 1.66-4.57), their frequency in the severe group were 71.8% (84/150) and 70.7% (58/150), respectively. We detected significant differences between TLR-4 (Asp299Gly, Thr399Ile) genotypes with regard to serum levels of IL-6. Levels of IL-6 increased significantly with the presence of the mutant 299Gly (G) and 399Ile (T) alleles to reach the highest levels in the Gly299Gly (GG) and the Ile399Ile (TT) genotypes (170 pg/mL (145-208.25) and 112 pg/mL (24-284.75), respectively). The TLR-4 (Asp299Gly and Thr399Ile) minor alleles 299Gly (G) and 399Ile (T) are associated with COVID-19 severity, mortality, and the cytokine storm.