Impact of comorbidities and genetic risk factors on hypercoagulation in patients with severe COVID‐19 infection

Abstract

Summary. Aim: to evaluate the impact of comorbid conditions and genetic risk factors on the development of hypercoagulation in patients with severe coronavirus disease (COVID‐19). Materials and Methods. A retrospective cohort study was conducted at an infectious diseases hospital between December 2020 and December 2021. The clinical cohort comprised 127 patients with severe COVID‐19 who were admitted to the intensive care unit. All patients underwent comprehensive evaluation, including electrocardiography, ultrasound examination of the heart, abdominal organs, and lower limb veins, coagulation testing, thrombodynamics test (ТDТ), and screening for venous thrombo‐ embolic events. In cases with suspected pulmonary embolism, computed tomography or chest radiography was performed. To identify genetic predictors of severe COVID‐19 and associated haemostatic disturbances, genotyping was carried out for three single nucleotide polymorphisms (SNPs) — rs17713054 and rs17078346 located in the SLC6A20–LZTFL1 locus, and rs12610495 in the DPP9 gene. These SNPs had previously been associated with a higher risk of critical COVID‐19 in the largest genome‐wide association studies (GWAS) meta‐analysis. Genotyping was performed by allele‐specific real‐time polymerase chain reaction in the Laboratory of Genomic Research, Research Institute of Genetic and Molecular Epidemiology, Kursk State Medical University. Results. Based on clinical outcomes, patients with severe COVID‐19 were divided into two groups: survivors (n = 68) and non‐survivors (n = 59). Among survivors, middle‐aged individuals predominated (50%), whereas elderly patients represented 47.4% of the non‐survivor group (χ2 = 23.62; p = 0.001). The following comorbidities were significantly more frequent among non‐survivors compared with survivors: hypertension — by 22.9% (p = 0.01), type 2 diabetes mellitus — by 19.0% (p = 0.01), obesity — by 22.2% (p = 0.03), atrial fibrillation — by 13.0% (p = 0.05), coronary artery disease — by 22.0% (p = 0.01), atheroscle‐ rosis of various localizations — by 40.8% (p = 0.01). Genetic analysis revealed that the single nucleotide polymorphisms rs17713054 in the enhancer region of SLC6A20–LZTFL1 (risk allele A, p = 0.01), rs17078346 in SLC6A20–LZTFL1 (risk allele C, p = 0.01) and rs12610495 in DPP9 (risk allele G, p = 0.0119), were associated with increased body mass index. Regarding the hypercoagulable profile observed in ТDТ, patients carrying the A allele of rs17713054 SLC6A20–LZTFL1 demonstrated elevated clot optical density (D) (p = 0.02) and prolonged time to spon‐ taneous clot appearance (p = 0.04). Conclusion. The presence of specific comorbid conditions — notably hypertension, type 2 diabetes mellitus, and obesity — in combination with minor allelic variants rs17713054 and rs17078346 (SLC6A20–LZTFL1) and rs12610495 (DPP9) previously associated with severe clinical manifestations of COVID‐19, contributes to the enhancement of plasma hypercoagulability, thereby adversely influencing disease outcomes.

For citation: Loktionov A.V., Sergeeva V.A., Bushueva O.Y., Trubnikova Е.V., Kuzovlev А.Е. Impact of comorbidities and genetic risk factors on hypercoagulation in patients with severe COVID‐19 infection. Tromboz, gemostaz i reologiya. 2025;(4):84–94. (In Russ.).

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