Levels of Fibrinogen Variants Are Altered in Severe COVID-19

AbstractBackground 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.