Levels of Fibrinogen Variants Are Altered in Severe COVID-19

Judith J. de Vries; Chantal Visser; Maureen van Ommen; Casper Rokx; Els van Nood; Eric C. M. van Gorp; Marco Goeijenbier; Johannes P. C. van den Akker; Henrik Endeman; Dingeman C. Rijken; Marieke J. H. A. Kruip; Miranda Weggeman; Jaap Koopman; Moniek P. M. de Maat

doi:10.1055/a-2102-4521

TH Open, Table of Contents

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

¹Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

,

Chantal Visser

¹Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

,

Maureen van Ommen

²Fibriant BV, Leiden, The Netherlands

,

Casper Rokx

³Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands

,

Els van Nood

³Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands

,

Eric C. M. van Gorp

⁴Department of Internal Medicine, Erasmus MC, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands

⁵Department of Viroscience, Erasmus MC, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands

,

Marco Goeijenbier

⁵Department of Viroscience, Erasmus MC, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands

⁶Department of Adult Intensive Care, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands

,

Johannes P. C. van den Akker

⁶Department of Adult Intensive Care, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands

,

Henrik Endeman

⁶Department of Adult Intensive Care, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands

,

Dingeman C. Rijken

¹Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

,

Marieke J. H. A. Kruip

¹Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

,

Miranda Weggeman

²Fibriant BV, Leiden, The Netherlands

,

Jaap Koopman

²Fibriant BV, Leiden, The Netherlands

,

Moniek P. M. de Maat

¹Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

› Author Affiliations

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 (α_E), 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 α_E fibrinogen than healthy controls (n = 7). The relative α_E 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 α_E 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

Full Text

References

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Supplementary Material

Supplementary Material