By Denise Baez
DG Alerts Anesthesiology
The expression of the procoagulant transferrin was higher in males, increased with age, and was upregulated upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, according to a study published in Diagnostics.
“The role of transferrin in the course of COVID-19 [coronavirus disease 2019] disease and in particular of COVID-19-related coagulopathy should be considered and further examined in ongoing clinico-pathological investigations,” wrote Katie-May McLaughlin, School of Biosciences, University of Kent, Canterbury, United Kingdom, and colleagues. “If the role of transferrin is confirmed in the pathogenesis of severe COVID-19 disease and in COVID-19-related coagulopathy, it is a candidate diagnostic marker for the monitoring of COVID-19 progression and may guide the use of anticoagulants in COVID-19 patients.”
For the study, the researchers performed a combined analysis of a proteomics dataset derived from SARS-CoV-2-infected cells, of a dataset of host cell proteins found to bind to SARS-CoV-2 proteins, and of human gene expression data from the Genotype-Tissue Expression (GTEx) database. Gene expression data and clinical data for 980 individuals were downloaded from the GTEx portal.
While searching for candidates potentially involved in COVID-19-related coagulopathy, the researchers found transferrin to be upregulated in SARS-CoV-2-infected cells relative to non-infected cells.
“Transferrin is a glycoprotein circulating in the blood that is best known for its function as an iron carrier,” the authors wrote. “It binds to cellular transferrin receptors and delivers iron by receptor-mediated endocytosis. However, transferrin has also been shown to increase coagulation independent of its role as an iron transporter by interfering with antithrombin/SERPINC1-mediated inhibition of coagulation proteases including thrombin and factor XIIa. Hence, there might be a link between transferrin levels and coagulation in patients with COVID-19.”
According to the authors, GTEx data indicated that transferrin expression increased with age and was higher in males than in females. In contrast, expression of its antagonist antithrombin, did not increase with age and was similar in females and males. Thus, the transferrin/antithrombin ratio increases with age and is higher in males than in females.
“This correlates with the risk of severe and fatal COVID-19 disease, which is higher in males than in females and also increases with age,” the authors wrote. “Hence, an increased transferrin/antithrombin ratio may contribute to COVID-19-related coagulopathy and more severe disease in older patients, in particular in males.”