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

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
• single-nucleotide polymorphism
• toll-like receptor
• high resolution-CT
• susceptibility
• severity

Abbreviations

TLRs, toll-like receptors; COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; ssRNA, single-stranded RNA; PAMPs, pathogen-associated molecular pattern; SNPs; single nucleotide polymorphisms; NETs, neutrophil extracellular traps; RT-PCR, reverse-transcriptase polymerase chain reaction; WHO, World Health Organization; IRB, institutional review board; CBC, complete blood count; CRP, C-reactive protein; MGB, minor groove binder; NFQ, non-fluorescent quenchers; AD, allele discrimination; HRCT, high resolution-CT; SPSS, statistical package for social sciences; HWE, Hardy-Weinberg equilibrium; OR, odds ratio; ESR, erythrocyte sedimentation rate; ALT, alanine transaminase; AST, aspartate transaminase.

Acknowledgments

We would like to express our thanks to all voluntary participants in this study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.