SERPINE1 rs6092 Variant Is Related to Plasma Coagulation Proteins in Patients with Severe COVID-19 from a Tertiary Care Hospital

SIMPLE SUMMARY: Severe forms of coronavirus disease 2019 (COVID-19) are related to an alteration in the coagulation process determined by genetic factors. Variability on F5 and SERPINE1 genes has been previously reported as a risk factor for thrombosis associated with different diseases. In this study, we aimed to evaluate if two relevant variants in the F5 and SERPINE1 genes were related to the requirement of invasive mechanical ventilation in hospitalized patients with COVID-19 and/or the levels of coagulation-related proteins. We observed that patients presenting the studied variants in F5 and SERPINE1 exhibit different levels of coagulation-related proteins. Moreover, the levels of these proteins were higher among patients requiring invasive mechanical ventilation when compared to hospitalized patients with no ventilation support. This study contributes to the genetics insight regarding COVID-19 severity and the inter-individual susceptibility for a severe form of the infectious disease. ABSTRACT: An impaired coagulation process has been described in patients with severe or critical coronavirus disease (COVID-19). Nevertheless, the implication of coagulation-related genes has not been explored. We aimed to evaluate the impact of F5 rs6025 and SERPINE1 rs6092 on invasive mechanical ventilation (IMV) requirement and the levels of coagulation proteins among patients with severe COVID-19. Four-hundred fifty-five patients with severe COVID-19 were genotyped using TaqMan assays. Coagulation-related proteins (P-Selectin, D-dimer, P-selectin glycoprotein ligand-1, tissue plasminogen activator [tPA], plasminogen activator inhibitor-1, and Factor IX) were assessed by cytometric bead arrays in one- and two-time determinations. Accordingly, SERPINE1 rs6092, P-Selectin (GG 385 pg/mL vs. AG+AA 632 pg/mL, p = 0.0037), and tPA (GG 1858 pg/mL vs. AG+AA 2546 pg/mL, p = 0.0284) levels were different. Patients carrying the CT F5-rs6025 genotype exhibited lower levels of factor IX (CC 17,136 pg/mL vs. CT 10,247 pg/mL, p = 0.0355). Coagulation proteins were also different among IMV patients than non-IMV. PSGL-1 levels were significantly increased in the late stage of COVID-19 (>10 days). The frequencies of F5 rs6025 and SERPINE1 rs6092 variants were not different among IMV and non-IMV. The SERPINE1 rs6092 variant is related to the impaired coagulation process in patients with COVID-19 severe.