Relevance of IFNAR2 variants in the mortality of patients with severe COVID-19

Background: The Interferon (IFN)-gamma pathway, including its receptor subunits (IFNAR1 and IFNAR2), is related to hyperinflammation and lower viral clearance in COVID-19. IFNAR2 and the soluble form of the protein have been associated with COVID-19 severity. Aim(s): We aimed to evaluate the association of the IFNAR2 rs2236757, rs1051393, rs3153, rs2834158, and rs2229207 with the clinical outcome (survivors and non-survivors) of patients with severe COVID-19. Method(s): The study included 1,136 patients (67% males, median 56 years old) with severe COVID-19, hospitalized in the Instituto Nacional de Enfermedades Respiratorias, a tertiary care hospital in Mexico. Variants were assessed using Taqman assays. The association study was performed using PLINK v2. Result(s): Four hundred and fifteen patients died during the hospital stay (36.5%). We found higher minor allele frequencies of the rs2236757, rs3153, and rs2834158 among non-survivors compared with survivors. The analyses of genotypes also showed associations of the dominant model for the three variants (Table 1). The rs2834158 was also associated with a logistic regression model adjusted for age (p= 0.038). Conclusion(s): IFNAR2 variants contribute to the genetic risk for mortality in patients with severe COVID-19. (Table Presented).

TNF, TNFRSF1A, and TNFRSF1B variants affect TNFR1 and TNFR2 levels in patients with severe COVID-19

Background: TNF and its receptors (TNFR1 and TNFR2) have been implicated in the severity of COVID-19. But it has not been explored the association of genetic variants with cytokine levels. Aim(s): We assessed the association of TNF (rs1800629, rs361525), TNFRSF1A (rs767455, rs1800693), and TNFRSF1B (rs1061622, rs3397) single nucleotide variants with TNF, TNFR1, and TNFR2 plasma levels in patients with severe COVID-19. Method(s): The study included 334 severe COVID-19 hospitalized patients in Mexico's Instituto Nacional de Enfermedades Respiratorias. Blood sampling was performed among the first seven days since patients' admission. Cytokine levels were determined using ELISA and Taqman assays for genotyping. Kruskal-Wallis test was performed in RStudio v.1.3.1073. Result(s): Patients with TT or GT genotype (TNFRSF1B rs1061622) exhibited higher sTNFR1 levels than those carrying GG (1,580 and 1,499 pg/ml vs 1,031 pg/mL). For TNF rs1800629 and rs361525 the higher TNFR2 levels were observed among patients homozygous for the common allele (rs1800629 GG=3,993 pg/mL vs AG+AA=2,881 pg/mL;rs361525 GG=3,996 pg/mL, AG=3,919 pg/mL, and AA=1,935 pg/mL). Higher levels of both receptors were related with more severe forms of COVID-19. Conclusion(s): TNFRSF1B rs1061622, and TNF rs1800629 and rs361525 affect the TNFR1 and TNFR2 levels implicated in the severity of COVID-19.