Impact of Toll-Like Receptor 2 and 9 Gene Polymorphisms on COVID-19: Susceptibility, Severity, and Thrombosis

Alshaymaa M Alhabibi; Asmaa S Hassan; Nashwa Mohamed Abd Elbaky; Hoda Asaad Eid; Mohie Aldeen Abd Alzaher Khalifa; Maisa A Wahab; Azza Ali Althoqapy; Aml E Abdou; Doaa Mohammed Zakaria; Eman Mostafa Nassef; Sammar Ahmed Kasim; Ola I Saleh; Asmaa Abdelghany Elsheikh; Mahmoud Lotfy; Alaa Sayed

doi:10.2147/JIR.S394927

Impact of Toll-Like Receptor 2 and 9 Gene Polymorphisms on COVID-19: Susceptibility, Severity, and Thrombosis

J Inflamm Res. 2023 Feb 17:16:665-675. doi: 10.2147/JIR.S394927. eCollection 2023.

Authors

Alshaymaa M Alhabibi¹, Asmaa S Hassan¹, Nashwa Mohamed Abd Elbaky¹, Hoda Asaad Eid², Mohie Aldeen Abd Alzaher Khalifa³, Maisa A Wahab⁴, Azza Ali Althoqapy⁵, Aml E Abdou⁵, Doaa Mohammed Zakaria⁶, Eman Mostafa Nassef⁶, Sammar Ahmed Kasim⁶, Ola I Saleh⁷, Asmaa Abdelghany Elsheikh⁸, Mahmoud Lotfy⁹, Alaa Sayed¹⁰

Affiliations

¹ Departments of Clinical Pathology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt.
² Chest Disease, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt.
³ Department of Chest Disease, General Organization for Teaching Hospitals and institutes, Cairo, Egypt.
⁴ Vascular Surgery, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt.
⁵ Medical Microbiology and Immunology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt.
⁶ Internal Medicine, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt.
⁷ Radio-Diagnosis, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt.
⁸ Community and Occupational Medicine, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt.
⁹ Molecular Biology Department, Genetic Engineering & Biotechnology Research Institute, University of Sadat City, Sadat City, Minufiya, Egypt.
¹⁰ Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt.

Abstract

Background: Toll-like receptors (TLRs) play an important role in activation of innate and adaptive immune responses.

Aim: We aimed to detect the association between TLR2 rs5743708 G>A and TLR9 rs5743836 C>T variants and COVID-19 disease susceptibility, severity, and thrombosis by using neutrophil extracellular traps (NETs).

Subjects and methods: We included 100 adult COVID-19 patients as well as 100 age- and gender-matched normal controls. Participants were genotyped for TLR2 rs5743708 and TLR9 rs5743836. Citrullinated Histone (H3) was detected as an indicator of NETs.

Results: The mutant (G/A and C/C) genotypes and (A and C) alleles of TLR2 rs5743708 and TLR9 rs5743836, respectively, have been significantly related to a higher risk of COVID-19 infection, representing a significant risk factor for the severity of COVID-19. There was no significant association between the two variants and citrullinated histone (H3).

Conclusion: TLR2 rs5743708 and TLR9 rs5743836 variants have been significantly related to a higher risk and severity of COVID-19 infection but had no effect on thrombus formation.

Keywords: coronavirus disease 2019; high resolution-CT; severity; single-nucleotide polymorphism; susceptibility; toll-like receptor.