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

Levels of Fibrinogen Variants Are Altered in Severe COVID-19

TH Open. 2023 Jul 13;7(3):e217-e225. doi: 10.1055/a-2102-4521. eCollection 2023 Jul.

Authors

Affiliations

¹ Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
² Fibriant BV, Leiden, The Netherlands.
³ Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
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.
⁶ Department of Adult Intensive Care, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.

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 γ' 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 γ' 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 γ' fibrinogen, which may be a cause or consequence of severe disease, but this is not associated with the development of thrombosis.

Keywords: COVID-19; fibrin; fibrinogen; inflammation; splicing.

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/ ).

Grants and funding

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).