VPB0612 - Angiostatin and Plasminogen Levels as Risk Factors for Mortality in Hospitalized Covid-19 Patients

Background: Covid-19-associated thrombotic complications are in part due to loss of plasminogen-associated fibrinolytic activity. Angiostatin is a break-down product of plasmin(ogen) with pro-apoptotic properties under hypoxia and acidosis, conditions associated with Covid-19. Hence, it may contribute to fatal outcome in Covid-19.

Aims: To assess the relationship between plasminogen/angiostatin levels and mortality in hospitalized Covid-19 patients.

Methods: Age- and sex-matched plasma samples (n=120) from Covid-19 survivors and non-survivors were obtained from Alberta Precision Laboratories (Canada). Angiostatin and plasminogen were quantified by immunoblot. Cox's proportional hazards regression model was used to determine the association between angiostatin/plasminogen levels and risk of death. Hazard ratios [HR] and 95% confidence intervals [CI] were estimated adjusting for time of sample collection (days from hospitalization to collection) and comorbidities (Charlson comorbidity score). The interaction between plasminogen/angiostatin levels and time of sample collection (before or after 7days from hospital admission) was assessed and stratified HRs were estimated.

Results: Overall, compared to survivors, non-survivors had a lower plasminogen level (mean±SD: 6.6±2.1 and 5.6±2.2 arbitrary units). Increase in plasminogen level was significantly associated with reduction in risk of death, independent of time of sample collection and comorbidities (Table1). When stratified by time of sample collection, the association remained significant only for samples drawn within 7 days of admission (Table2). Conversely, an overall difference was not observed in angiostatin concentrations (mean±SD: 136.0±42.5 and 143.0±48.9 μg/ml), and it was not associated with survival outcome (Table1). However, when stratified by time of collection and adjusted for comorbidity burden, angiostatin was significantly associated with an increased risk of death for samples collected after 7days from admission (Table2).

Conclusion(s): Both angiostatin and plasminogen were associated with fatal outcome in Covid-19, independent of comorbidities. These associations depended on the time from hospital admission to sample collection and likely reflect dynamic changes in the plasminogen-angiostatin generation system associated with Covid-19 disease progression.