Contact system and intrinsic pathway are activated and associated with clinical and laboratory outcomes in COVID-19patients

Background : Hemostasis activation is considered a key pathogenic element of COVID-19, as evidenced by the frequency of lung microvascular thrombosis and of venous thromboembolism. As shown in other conditions, pathways that mediate hemostasis activation during inflammation are not necessarily the same as those that drive hemostasis in non-inflammatory states. In particular, contact system and intrinsic pathway activation have been increasingly explored as potential mediators of hemostasis activation and prothrombotic states observed in both sterile and infectious inflammatory conditions. Aims : To assess the activation of contact system and intrinsic pathway activation in COVID-19. Methods : Protease:serpin complexes were measured in plasma from inpatients with COVID-19 and healthy individuals (HI). All samples were collected within 24 h of COVID-19 diagnosis. Associations with laboratory and clinical markers of hemostasis activation and disease severity were explored. The study was approved by the IRB and all participants provided written informed consent. Results : In total, 30 patients with COVID-19 and 30 age and sex-matched HI were enrolled. Main characteristics of the study population are shown in Table 1. As expected, higher levels of classical coagulation activation parameters were observed in COVID-19 patients. Contact system and intrinsic pathway activation in COVID-19 was demonstrated by increased levels of several protease:serpin complexes (Table 2). Interestingly, a consistent and significant association was observed between FIXa:antithrombin complexes with both clinical endpoints (need of ICU admission, length of ICU stay, total length of stay and extent of lung CT alterations), and with laboratory markers of immunothrombosis (neutrophil:lymphocyte ratio, C-reactive protein, D-dimer, PAP, VWF:Ag), as well as with several other activation markers of contact system and intrinsic pathway Conclusions : Contact system and intrinsic pathway activation contribute to hemostasis activation in COVID-19. The association of FIXa:antithrombin complexes with disease severity suggests that these pathways contribute to the pathogenesis of the prothrombotic state of COVID-19.