ArticleFrontiers in immunology2025
Association of pro-inflammatory and anti-inflammatory cytokine polymorphisms with COVID-19 severity in unvaccinated patients.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Cytokine profiles, genetic polymorphisms, and systemic inflammatory markers in type 1 diabetes patients with COVID-19: IL-18 a predictor of disease severity.Frontiers in immunology · 2026Article
- Imbalanced immune cell network and suboptimal cell activation: signatures associated with disease severity in vaccine-naïve COVID-19 patients.Frontiers in immunology · 2026Article
- Genetic Variants in CytokinesLife (Basel, Switzerland) · 2025Article
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Authors and funding
29 authors.
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Abstract
Background: Cytokines and chemokines are essential for establishing an appropriate immune response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Variations in the genes encoding cytokines and chemokines strongly influence the immune response to pathogenic challenges and disease outcomes. This study was conducted to investigate the associations between polymorphisms in the Methodology: We performed a cross-sectional study with a total of 627 unvaccinated COVID-19 patients were classified according to WHO disease severity. We evaluated the levels of IFN-α, IFN-γ, TNF-α, IL-1Ra, IL-2, IL-6, IL-7, IL-10, CCL2, CCL3, CXCL8, CXCL10 and GCSF in the serum and compared them among COVID-19 severity groups by Kruskal-Wallis test and stratified by polymorphism alleles. A logistic regression was performed to determine the association of the polymorphism and COVID-19 severity. Results: This study revealed a significant increase in IL-2, IL-6 and CCL-2 levels in the deceased group. However, the IL-10 levels were higher in the moderate group than in the mild group. Logistic regression analysis revealed that five polymorphisms were associated with a higher risk of severe COVID-19: the Conclusion: Patients infected with SARS-CoV-2 who have the TNFα gene variant (rs1800629) are protected from developing COVID-19 moderate and severe outcomes, as well as from presenting low concentrations of some pro-inflammatory cytokines and chemokines. However, carriers of the IL-10 (rs1800872, rs1800871) and CCL-5 (rs2107538) gene variants were associated with patients who died from COVID-19. Of these, only the minor allele of CCL-5 was primarily associated with increased chemokines levels, as well as with some cytokines considered hallmarks of the cytokine storm.
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