Association of TLR9-rs352140 Polymorphism and Serum Levels of CRP, IL-6, and Anti-RBD IgG with the Chance of [Long COVID] , 2025, Alavitabar et al

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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

Zeynab Alavitabar, Hamed Fouladseresht, Amaneh Javid, Ensiye Torki, Majid Hosseinzadeh

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. The TT genotype and T allele of the TLR9-rs352140 polymorphism were more common in the LCS+ group, while anti-RBD IgG levels and the CC genotype were lower. Logistic regression indicated that history of severe COVID-19, higher IL-6 and CRP levels, and the T allele of TLR9-rs352140 were significantly associated with an increased risk of LCS. Conversely, higher anti-RBD IgG levels and the C allele were linked to a reduced risk.

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.

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