Association of TLR9-rs352140 Polymorphism and Serum Levels of CRP, IL-6, and Anti-RBD IgG with the Chance of Developing Long COVID-19 Syndrome

Abstract

Background: Long COVID-19 syndrome (LCS) is characterized by a wide array of symptoms persisting for at least three months after the acute phase of COVID-19. The etiology and risk factors associated with LCS remain poorly understood. This study aimed to investigate the relationship between demographic characteristics, hospitalization history, laboratory parameters, and the TLR9-rs352140 single-nucleotide polymorphism in relation to the risk of developing LCS. Methods: We collected demographic and hospitalization data from medical records of 88 individuals with LCS (LCS+ group) and 96 without LCS (LCS-group). Serum levels of interleukin-6 (IL-6) and anti-receptor binding domain IgG (anti-RBD IgG) were measured using ELISA, and the TLR9-rs352140 polymorphism was genotyped via ARMS-PCR. Findings: The LCS+ group showed a significantly higher prevalence of severe COVID-19 history, along with elevated serum levels of C-reactive protein (CRP) and IL-6, compared to the LCS-group (P < 0.001, P = 0.005, and P < 0.001; respectively). Furthermore, the TT genotype and T allele of the TLR9-rs352140 polymorphism were more common in the LCS+ group (P = 0.021 and P = 0.002; respectively). Conversely, the serum level of anti-RBD IgG and the frequency of the CC genotype and C allele were lower (P < 0.001, P = 0.010, and P = 0.002; respectively). Multivariate logistic regression analysis indicated that a history of severe COVID-19, higher CRP and IL-6 levels, and the T allele of TLR9-rs352140 were significantly associated with an increased risk of LCS (P = 0.001, P = 0.003, P = 0.002, and P = 0.018; respectively). While, higher anti-RBD IgG levels and the C allele were linked to a reduced risk of LCS (P < 0.001 and P < 0.018; respectively). Conclusion: A history of severe COVID-19, higher serum IL-6 and CRP levels, and the T allele of the TLR9-rs352140 polymorphism are positively correlated with the risk of developing LCS. © 2025, Isfahan University of Medical Sciences(IUMS). All rights reserved.