The link between inflammation, coagulation and endothelium damage in COVID-19: Evidence from an exploratory crosssectional study

ABSTRACT

Background: Increasing evidence suggests that endothelial activation and dysfunction contribute to COVID-19 pathogenesis by altering vessel integrity, promoting pro-coagulative and inflammatory state. Aims: 1. Investigate changes in coagulation, inflammation and endothelium associated with the progression and severity of COVID-19, as well as their correlation to survival and/or occurrence of venous thromboembolic events (VTE). 2. Explore potential new biomarkers to predict COVID-19 severity. Methods: Samples were collected from COVID-19 patients after appropriate consent. Disease severity was assessed with WHO ordinal scale on day of sampling. In addition to routine haematology, biochemistry and coagulation analysis, additional analysis spanning coagulation, endothelium, platelet, inflammatory biomarkers by conventional assays and multiplex immuno-assays were undertaken. Results: Participants included 151 COVID-19 patients aged 18 years and greater, 16 healthy volunteers and 9 non-COVID-19 ICUcontrols. COVID-19 patients were categorised in 7 groups based on severity and time from symptom onset and the data also provides mortality and VTE rates (Table 1). The biomarker profile of hospitalised COVID-19 patients demonstrated an increase in plasma levels of cytokines, inflammatory, soluble endothelial cell markers and markers of coagulation activation when compared to the ambulatory group (Figure 1). Significantly higher levels of inflammatory markers (CRP, WBC, fibrinogen, serum amyloid P, alpha 1 acid glycoprotein) were observed in patients with VTE and in the non-survivors group. Interestingly, the same trend was seen for coagulation (FVIII, VWF) and fibrinolysis markers (D-dimer, TFPI, t-PA) with higher levels in the VTE and non-survivors group. In addition, higher plasma levels of endothelial markers (ICAM-1, angiopoietin, TIE-2, LYVE-1, syndecan) were observed in severe COVID-19 when compared to non-COVID-19 ICU-controls. (Figure Presented) Conclusions: Our study provides evidence of a strong, global inflammatory response in COVID-19 patients. The elevation of circulating markers suggests significant endothelial cell activation/dysfunction and a possible cause for the pro-coagulant phenotype observed in these patients.