Prognostic Genetic Markers for Thrombosis in COVID-19 Patients: A Focused Analysis on D-Dimer, Homocysteine and Thromboembolism

Abstract

COVID-19 is caused by Severe Acute Respiratory Syndrome Coronavirus-2, which has infected over thirty eight million individuals worldwide. Emerging evidence indicates that COVID-19 patients are at a high risk of developing coagulopathy and thrombosis, conditions that elevate levels of D-dimer. It is believed that homocysteine, an amino acid that plays a crucial role in coagulation, may also contribute to these conditions. At present, multiple genes are implicated in the development of these disorders. For example, single-nucleotide polymorphisms (SNPs) in FGG, FGA, and F5 mediate increases in D-dimer and SNPs in ABO, CBS, CPS1 and MTHFR mediate differences in homocysteine levels, and SNPs in TDAG8 associate with Heparin-induced Thrombocytopenia. In this study, we aimed to uncover the genetic basis of the above conditions by examining genome-wide associations and tissue-specific gene expression to build a molecular network. Based on gene ontology, we annotated various SNPs with five ancestral terms: pulmonary embolism, venous thromboembolism, vascular diseases, cerebrovascular disorders, and stroke. The gene-gene interaction network revealed three clusters that each contained hallmark genes for D-dimer/fibrinogen levels, homocysteine levels, and arterial/venous thromboembolism with F2 and F5 acting as connecting nodes. We propose that genotyping COVID-19 patients for SNPs examined in this study will help identify those at greatest risk of complications linked to thrombosis.

Combined triple treatment of fibrin amyloid microclots and platelet pathology in individuals with Long COVID/ Post-Acute Sequelae of COVID-19 (PASC) can resolve their persistent symptoms

“…Homozygosity for the MTHFR 677C>T (rs1801133) variant or compound heterozygosity with 1298A>C (rs1801131) is the most common genetic cause of high homocysteine previously studied in COVID-19 patients 30 . The cut-off value of homocysteine to predict progression of pathological findings in chest CT-imaging of COVID-19 patients was 10.58 µmol/L, compared to the usual definition of high values above 15 µmol/L 31 .…”

Plasma S-Adenosylmethionine Is Associated with Lung Injury in COVID-19

“…A recent report suggested the role of high Hcy levels as a risk factor for severity or complications in COVID-19 [ 16 , 17 ]. Another study showed a significant correlation between Hcy levels and imaging progression on chest computed tomography (CT) from COVID-19 patients [ 18 ].…”

Autoimmunity roots of the thrombotic events after COVID-19 vaccination

“…As with the highly variable probability of SARS-CoV-2 infection, different populations and individuals will likely respond uniquely to the SARS-CoV-2 vaccine, simply because the main viral antigen inducing pathophysiology associated with infection is the spike glycoprotein, which represents the main viral component in those vaccines that induce VITT, due at least in part to genetic variations. The genetic analysis revealed a list of SNPs and genes that can be used as biomarkers to predict the development of coagulation [ 65 , 66 ].…”