High nasopharyngeal and serum IL-6 levels and the − 573G > C polymorphism (rs1800796) are linked with the risk of severe COVID-19 in a Mexican population: a case‒control study

Abstract

Background

COVID-19 was the leading cause of death in Mexico between 2020 and 2021. SARS-CoV-2 infection varies widely among individuals and populations. Since variations in genes related to the immune response may play a role in the susceptibility to and outcome of COVID-19, the associations of gene polymorphisms (SNPs) of IL-6 (− 573G > C, rs1800796), TNF-α (− 308G > A, rs1800629), and IFN-γ (− 1615 C > T, rs2069705) with the expression levels of these proteins in the nasopharynx and serum were evaluated in a Mexican population with mild, severe, or critical COVID-19.

Methods

A total of 560 COVID-19 patients (309 mild, 163 severe, and 88 critical cases) and 560 age- and sex-matched COVID-19-negative controls were recruited for this case‒control study. The selected SNPs were genotyped via allelic discrimination. Logistic regression analysis was conducted considering four models of inheritance, and ORs were determined for each genotypic variant, adjusting for associated comorbidities in the multivariate model. The nasopharyngeal mRNA expression levels of IL-6, IFN-γ and TNF-α were determined. The levels of IL-6, IFN-γ, IFN-α2, and TNF-α in the serum were quantified. Significant differences were assessed via the Wilcoxon Mann‒Whitney U test.

Results

The C allele of the IL-6 − 573 SNP was associated with a greater risk of mild and severe COVID-19 (OR: 2.3, CI: 1.897–2.838, p = 0.0001; and OR: 1.5, CI: 1.167–1.949, p = 0.002, respectively), whereas the A allele of the TNF-α − 308 SNP and the T allele of the IFN-γ − 1615 SNP were shown protective roles against severe COVID-19 (OR: 0.3, CI: 0.189–0.537, p = 0.0001; and OR: 0.7, CI: 0.563–1.006, p = 0.05) and against critical COVID-19 (OR: 0.3, CI: 0.158–0.640, p = 0.001; and OR: 0.4, CI: 0.290–0.678, p = 0.0001), adjusting for diabetes and hypertension. Nasopharyngeal IL-6 expression levels were lower in mild COVID-19 patients (p = 0.001) than in critical patients (p = 0.005). Serum IL-6 levels were significantly elevated in the critical cases (p = 0.01).

Conclusions

Our results revealed that the IL-6 − 573 G > C SNP and increased IL-6 nasopharyngeal and serum levels are associated with the risk of severe COVID-19 in a Mexican population.