Association of pro-inflammatory and anti-inflammatory cytokine polymorphisms with COVID-19 severity in unvaccinated patients.
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Martínez-Gómez Laura E, Oropeza-Vélez Carla I, Almonte-Becerril Maylin, Chavez-Galan Leslie, Martinez-Armenta Carlos, Vidal-Vázquez Rosa P, Ramírez-Hinojosa Juan P, Vázquez-Cárdenas Paola, Gómez-Martín Diana, Vargas-Alarcón Gilberto, Rodríguez-Pérez José M, Ramón-Luing Lucero A, Flores-Gonzalez Julio, Carrasco José G, Cruz-Bautista Ivette, Mata-Miranda Mónica M, Vázquez-Zapién Gustavo J, Martínez-Cuazitl Adriana, Parra-Torres Nancy M, Martínez-Ruiz Felipe de J, Zayago-Angeles Dulce M, Ordoñez-Sánchez Ma Luisa, Segura-Kato Yayoi, Suarez-Ahedo Carlos, Olea-Torres Jessel, Herrera-López Brígida, Pineda Carlos, Martínez-Nava Gabriela A, López-Reyes Alberto G
Аннотация
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.