Journal of Inflammation Research (Nov 2021)

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

  • Taha SI,
  • Shata AK,
  • Baioumy SA,
  • Fouad SH,
  • Anis SG,
  • Mossad IM,
  • Moustafa NM,
  • Abdou DM,
  • Youssef MK

Journal volume & issue
Vol. Volume 14
pp. 6293 – 6303

Abstract

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Sara I Taha,1 Aalaa K Shata,2 Shereen A Baioumy,3 Shaimaa H Fouad,4 Sherif G Anis,5 Isis M Mossad,6 Nouran M Moustafa,7,8 Dina M Abdou,9 Mariam K Youssef1 1Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 2Department of Pulmonary Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 3Department of Microbiology and Immunology, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 4Department of Internal Medicine/Allergy and Clinical Immunology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 5Department of Anesthesia and Intensive Care, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 6Department of Community, Environmental and Occupational Medicine, Faculty of Medicine Ain Shams University, Cairo, Egypt; 7Department of Basic Medical Science, Faculty of Medicine, Dar Al Uloom University, Riyadh, Saudi Arabia; 8Department of Microbiology and Immunology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 9Department of Internal Medicine/Hematology, Faculty of Medicine, Ain Shams University, Cairo, EgyptCorrespondence: Sara I TahaDepartment of Clinical Pathology, Faculty of Medicine, Ain Shams University, Abassia, Cairo, EgyptTel + 20 1125360009Fax + 20 2 24346308Email [email protected]: 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.Objective: 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.Methods: 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.Results: 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).Conclusion: The TLR-4 (Asp299Gly and Thr399Ile) minor alleles 299Gly (G) and 399Ile (T) are associated with COVID-19 severity, mortality, and the cytokine storm.Keywords: COVID-19, Egypt, mortality, polymorphism, severity, Toll-like receptor

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