ABSTRACT
Background: In coronavirus disease 2019 (COVID-19) the need for intervention increases with disease severity and a risk prediction model that incorporates biomarkers would be beneficial for identifying patients for treatment escalation. Aim(s): To investigate biomarkers changes associated with disease severity and outcomes (mortality, thrombosis). Method(s): COVID-19 patients were sampled between April 15 and May 31 2020. Disease severity was assessed by World Health Organization (WHO) ordinal scale. 132 systemic biomarkers were investigated by routine and multiplex assays and statistical analysis performed to characterise the biomarker profile of COVID-19 patients associated with disease severity, duration, survival and thrombosis. Result(s): The study enrolled 150 COVID-19 positive adults and 16 healthy volunteers. The average age was 64 years, 59% were male, 85% had co-morbidities, 33% had a thrombotic event, and 13% died. A cross comparative analysis of biomarkers identified 13 biomarkers common to severity, mortality and thrombosis with significant correlation;including endothelial dysfunction (VWF, tPA, TFPI), hypercatabolism (low albumin, Hb, FXIII) and inflammatory response (IL-8, Osteopontin). Similarly, 14 biomarkers associated with severity and mortality included pro-inflammatory cytokines and their receptors (sTNFRII, STNFRI, sIL2a, IL6, MIP1a), neutrophils (elevated WBC, Neutrophils, TIMP1) and tissue remodelling (SCGF, EG3A). Nine biomarkers common across severity and thrombosis were angiogenesis (VEGF, LYVE1, Follistatin), acute phase response (SAP, AGP) and clot formation (Fibrinogen and PAPs). Conclusion(s): The biomarker profile associated with poorer outcomes indicates an inflammatory response, endothelial cell disruption, hypercoagulability and hypercatabolism. This study has identified several biomarkers that may be useful indicators of disease severity and progression. Further work is needed to determine how these may be used to direct clinical management. (Figure Presented).
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.