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Author Notes:

Ashley Brown, Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina at Chapel‐Hill, 1001 William Moore Dr, Raleigh, NC 27606, USA.

N.M. performed experiments, analyzed results, and wrote the paper; N.Z. assisted in clot structure and degradation experiments; R.S. and F.S. assisted in research design and paper writing; and A.C.B. designed and supervised the study, performed data analysis, and wrote the paper.

A.C.B. is founder and chief executive officer of Selsym Biotech, Inc., a startup company focused developing fibrin‐targeted hemostatic agents. All other authors declare no competing financial interests.

Subjects:

Research Funding:

Research reported in this publication was supported in part by Imagine, Innovate and Impact (I3) Funds from the Emory School of Medicine and through the Georgia CTSA NIH award (UL1‐TR002378), NIH R01HL146701, NIH 5T34GM131947, and NIH 1F30HL163869.NIH1F30HL1638695T34GM131947R01HL146701UL1‐TR002378

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Hematology
  • Peripheral Vascular Disease
  • Cardiovascular System & Cardiology
  • coagulopathy
  • COVID-19
  • fibrinogen
  • sialic acid
  • thrombosis
  • DISEASE

COVID-19 patient fibrinogen produces dense clots with altered polymerization kinetics, partially explained by increased sialic acid

Tools:

Journal Title:

JOURNAL OF THROMBOSIS AND HAEMOSTASIS

Volume:

Volume 20, Number 12

Publisher:

, Pages 2909-2920

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: Thrombogenicity is a known complication of COVID-19, resulting from SARS-CoV-2 infection, with significant effects on morbidity and mortality. Objective: We aimed to better understand the effects of COVID-19 on fibrinogen and the resulting effects on clot structure, formation, and degradation. Methods: Fibrinogen isolated from COVID-19 patients and uninfected subjects was used to form uniformly concentrated clots (2 mg/ml), which were characterized using confocal microscopy, scanning electron microscopy, atomic force microscopy, and endogenous and exogenous fibrinolysis assays. Neuraminidase digestion and subsequent NANA assay were used to quantify sialic acid residue presence; clots made from the desialylated fibrinogen were then assayed similarly to the original fibrinogen clots. Results: Clots made from purified fibrinogen from COVID-19 patients were shown to be significantly stiffer and denser than clots made using fibrinogen from noninfected subjects. Endogenous and exogenous fibrinolysis assays demonstrated that clot polymerization and degradation dynamics were different for purified fibrinogen from COVID-19 patients compared with fibrinogen from noninfected subjects. Quantification of sialic acid residues via the NANA assay demonstrated that SARS-CoV-2-positive fibrinogen samples contained significantly more sialic acid. Desialylation via neuraminidase digestion resolved differences in clot density. Desialylation did not normalize differences in polymerization, but did affect rate of exogenous fibrinolysis. Discussion: These differences noted in purified SARS-CoV-2-positive clots demonstrate that structural differences in fibrinogen, and not just differences in gross fibrinogen concentration, contribute to clinical differences in thrombotic features associated with COVID-19. These structural differences are at least in part mediated by differential sialylation.

Copyright information:

© 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/).
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