Association of pro-inflammatory and anti-inflammatory cytokine polymorphisms with COVID-19 severity in unvaccinated patients
Year: 2025
Type: article
Study design: Observational Study
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 TNF-α, IL-6, IL-8, IL-10, and CCL5 genes and COVID-19 severity. 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 TNF-α (rs1800610) A allele (OR=1.50; 95% CI: 1.01–2.24); the IL-6 (rs1800796) C allele (OR=1.64; 95% CI: 1.05–2.57); the IL-10 (rs1800871) T allele (OR=1.94; 95% CI: 1.24–3.04) and (rs1800872) A allele (OR=1.87; 95% CI: 1.21–2.89); and the CCL5 (rs3817656) G allele (OR= 1.64; 95% CI: 1.02–2.65). 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.
Source: Frontiers in Immunology
Authors: Laura E. Martínez-Gómez, Carla I. Oropeza-Vélez, Maylin Almonte-Becerril, Leslie Chavez-Galan, Carlos Martinez-Armenta, Rosa P. Vidal-Vázquez, Juan P. Ramírez-Hinojosa, Paola Vázquez-Cárdenas, Diana Gómez-Martín, Gilberto Vargas-Alarcón, José M. Rodríguez-Pérez, Lucero A. Ramón-Luing, Julio Flores-Gonzalez, José G. Carrasco, Ivette Cruz-Bautista, Mónica M. Mata-Miranda, Gustavo J. Vázquez-Zapién, Adriana Martínez-Cuazitl, Nancy M. Parra-Torres, Felipe de J. Martínez-Ruiz, Dulce M. Zayago-Angeles, Ma. Luisa Ordoñez-Sánchez, Yayoi Segura-Kato, Carlos Suarez-Ahedo, Jessel Olea-Torres, Brígida Herrera-López, Carlos Pineda, Gabriela A. Martínez-Nava, Alberto G. López-Reyes
Institutions: Secretaria de Salud, Instituto Nacional de Rehabilitación, Pemex (Mexico), Universidad de la Salud, Instituto Nacional de Enfermedades Respiratorias, Hospital General Dr. Manuel Gea Gonzalez, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Instituto Nacional de Cardiología, Universidad del Ejército y Fuerza Aérea, Institute for Social Security and Services for State Workers
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
Awards: G1047565609, G4684879392
OpenAlex ID: W4413179704