Increased percentage of extended Aalpha chain fibrinogen (alphaE) in COVID-19 patients

ABSTRACT

Background: Variation in fibrinogen caused by degradation or extension of the Aalpha chain affects the fibrin network structure and interaction of fibrin(ogen) with cells. The plasma level of these fibrinogen variants might be altered during COVID-19, potentially affecting disease severity or the risk of thrombosis. Aim(s) To investigate the level of fibrinogen Aalpha chain variants in plasma of COVID-19 patients. Method(s) Using the Clauss assay, we measured plasma levels of functional fibrinogen. ELISAs were used to measure antigen levels of total, intact (non-degraded Aalpha chain), and extended Aalpha chain fibrinogen (alphaE) in intensive care unit (ICU) patients with COVID-19 (with and without thrombosis, at two time points), COVID-19 ward patients without thrombosis, ICU patients with pneumococcal infection, and healthy controls. Ethical approval was obtained and written informed consent was obtained or an opt-out procedure was in place. Result(s) Higher levels of functional and intact fibrinogen were observed in COVID-19 ICU patients (before diagnosis of thrombosis) with (n = 18) and without thrombosis (n = 19) and ICU patients with pneumococcal infection (n = 6) than in COVID-19 ward patients (n = 10) and healthy controls (n = 7) (Figure 1). Total fibrinogen levels were higher in all ICU patients compared to healthy controls. Interestingly, the percentage of alphaE fibrinogen was significantly higher in COVID-19 ICU patients who do and do not develop thrombosis than in healthy controls. COVID-19 ICU patients who develop thrombosis also showed significantly higher percentages of alphaE fibrinogen than COVID-19 ward patients. After diagnosis of thrombosis, functional fibrinogen levels were significantly higher in COVID-19 ICU patients with thrombosis than in those without, while no differences were observed in intact, total, or alphaE fibrinogen (Figure 2). Conclusion(s) Our results show that severe COVID-19 is associated with increased percentages of alphaE fibrinogen, which may be the cause or consequence of severe disease, but does not explain the development of thrombosis. (Figure Presented).