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CC BY 4.0 · TH Open 2023; 07(03): e217-e225
DOI: 10.1055/a-2102-4521
Original Article

Levels of Fibrinogen Variants Are Altered in Severe COVID-19

Judith J. de Vries 
1   Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
,
Chantal Visser 
1   Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
,
Maureen van Ommen
2   Fibriant BV, Leiden, The Netherlands
,
Casper Rokx
3   Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands
,
Els van Nood
3   Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands
,
Eric C. M. van Gorp
4   Department of Internal Medicine, Erasmus MC, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands
5   Department of Viroscience, Erasmus MC, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands
,
Marco Goeijenbier
5   Department of Viroscience, Erasmus MC, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands
6   Department of Adult Intensive Care, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands
,
Johannes P. C. van den Akker
6   Department of Adult Intensive Care, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands
,
Henrik Endeman
6   Department of Adult Intensive Care, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands
,
Dingeman C. Rijken 
1   Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
,
Marieke J. H. A. Kruip
1   Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
,
Miranda Weggeman
2   Fibriant BV, Leiden, The Netherlands
,
Jaap Koopman
2   Fibriant BV, Leiden, The Netherlands
,
Moniek P. M. de Maat 
1   Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
› Author Affiliations Funding This work was supported by the Netherlands Thrombosis Foundation (Grant/Award Number: 2020_A) and the Netherlands Organization for Health Research and Development (Grant/Award Number: 10430012010004).
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Abstract

Background Fibrinogen variants as a result of alternative messenger RNA splicing or protein degradation can affect fibrin(ogen) functions. The levels of these variants might be altered during coronavirus disease 2019 (COVID-19), potentially affecting disease severity or the thrombosis risk.

Aim To investigate the levels of fibrinogen variants in plasma of patients with COVID-19.

Methods In this case-control study, we measured levels of functional fibrinogen using the Clauss assay. Enzyme-linked immunosorbent assays were used to measure antigen levels of total, intact (nondegraded Aα chain), extended Aα chain (αE), and γˊ fibrinogen in healthy controls, patients with pneumococcal infection in the intensive care unit (ICU), ward patients with COVID-19, and ICU patients with COVID-19 (with and without thrombosis, two time points).

Results Healthy controls and ward patients with COVID-19 (n = 10) showed similar fibrinogen (variant) levels. ICU patients with COVID-19 who later did (n = 19) or did not develop thrombosis (n = 18) and ICU patients with pneumococcal infection (n = 6) had higher absolute levels of functional, total, intact, and αE fibrinogen than healthy controls (n = 7). The relative αE fibrinogen levels were higher in ICU patients with COVID-19 than in healthy controls, while relative γˊ fibrinogen levels were lower. After diagnosis of thrombosis, only the functional fibrinogen levels were higher in ICU patients with COVID-19 and thrombosis than in those without, while no differences were observed in the other fibrinogen variants.

Conclusion Our results show that severe COVID-19 is associated with increased levels of αE fibrinogen and decreased relative levels of γˊ fibrinogen, which may be a cause or consequence of severe disease, but this is not associated with the development of thrombosis.

Keywords

splicing - COVID-19 - fibrinogen - fibrin - inflammation

Author Contributions

Judith J. de Vries: conceptualization, investigation, formal analysis, visualization, writing—original draft. Chantal Visser: conceptualization, investigation, writing—review and editing. Maureen van Ommen: investigation, writing—review and editing. Casper Rokx: resources, writing—review and editing. Els van Nood: resources, writing—review and editing. Eric C.M. van Gorp: conceptualization, writing—review and editing. Marco Goeijenbier: resources, writing—review and editing. Johannes P.C. van den Akker: resources, writing—review and editing. Henrik Endeman: conceptualization, resources, writing—review and editing. Dingeman C. Rijken: methodology, supervision, writing—review and editing. Marieke J.H.A. Kruip: conceptualization, resources, writing (review and editing), supervision, funding acquisition. Miranda Weggeman: conceptualization, methodology, resources, writing (review and editing), supervision. Jaap Koopman: conceptualization, methodology, resources, writing (review and editing), supervision. Moniek P.M. de Maat: conceptualization, writing (review and editing), supervision.


Supplementary Material



Publication History

Received: 04 July 2022

Accepted: 28 April 2023

Accepted Manuscript online:
29 May 2023

Article published online:
13 July 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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