COVID-19 may lead to post-acute COVID syndrome or long COVID, characterized by persistent symptoms lasting weeks to months after acute SARS-CoV-2 infection. Long COVID appears to be associated with persistent alterations in the inflammatory response. Genetic variations such as the IL18 rs1946518 (G/T) polymorphism may influence inflammatory diseases. This study evaluated the association of IL18 rs1946518 (G/T) with long COVID and its influence on plasma TNF-α and IL-6 levels.

The study included 71 blood samples from individuals with long COVID and 71 from individuals without long COVID. DNA extraction and genotyping for IL18 rs1946518 (G/T) were performed using real-time PCR. TNF-α and IL-6 levels were measured by flow cytometry. Statistical analyses were conducted using chi-square and Mann-Whitney tests.

Both groups showed higher frequency of the heterozygous polymorphic genotype (GT), with 50.7% in the long COVID group and 42.25% in the non–long COVID group. The wild-type allele (G) was more frequent in both groups. No differences were observed in genotype or allele frequencies between groups (p > 0.05). Individuals with long COVID had higher TNF-α and IL-6 levels compared to those without long COVID (p = 0.0003; p < 0.0001, respectively). TNF-α levels were higher in individuals carrying polymorphic genotypes in the long COVID group (p = 0.0120), while IL-6 levels did not differ between genotypes (p > 0.05).

The IL18 rs1946518 (G/T) polymorphism does not appear to be associated with the development of long COVID or IL-6–mediated response. However, it may contribute to increased TNF-α–mediated inflammation in long COVID patients, potentially influencing symptom intensity.