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.
Highlights
The COVID-19 outbreak, which began in China’s Hubei Province, was declared a pandemic by the World Health Organization on March 11, 2020
For children infected with SARS-CoV2, a two to three-fold increase in D-dimer levels has been observed as the disease progressed from mild to moderate (Qiu et al, 2020), and those with obesity are presumed to be at highest risk of complications from this virus because obese children are reported to have higher D-dimer levels
There is emerging evidence that coagulopathy and thrombosis are a common finding besides pneumonia in patients suffering from COVID-19, especially in severe courses
Summary
The COVID-19 outbreak, which began in China’s Hubei Province, was declared a pandemic by the World Health Organization on March 11, 2020. Pneumonia and shortness of breath were believed to be the primary causes of death in COVID-19 patients, yet growing research reveals that thrombosis, a consequence of the deterioration of coagulation factors, may be the leading offender (Becker, 2020; Bikdeli et al, 2020; Levi et al, 2020; Tang et al, 2020; Yuki et al, 2020; Zhou et al, 2020). Elevated levels of D-dimer represent the initial manifestation of coagulopathy in critically ill patients, followed by abnormal prothrombin and partial thromboplastin times, and low platelet counts in later stages (Connors and Levy, 2020; Iba et al, 2020)
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