Endothelial damage in COVID-19

Damage to endothelial tissue (endotheliopathy) is evident in COVID-19, data from a single-centre cross-sectional study suggest, and is likely to be associated with critical illness and death. Blood levels of soluble thrombomodulin correlate with mortality.

Dr George Goshua (Yale University, USA) presented the data, which followed up on the observation in SARS-CoV-2-infected individuals of a marked increase of clinical thrombotic and microvascular complications, referred to as COVID-19-associated coagulopathy (CAC) [1].

Despite thromboprophylaxis, CAC is still highly prevalent among hospitalised patients, with venous thromboembolism detected in 17% to 69% of patients. Furthermore, autopsy findings have shown microvascular thrombosis in as many as 87% of patients. The aetiology is unknown.

Dr Goshua and colleagues assessed endothelial cell damage, platelet activation, and haemostatic and fibrinolytic cascade effects of CAC in stable and critically ill patients hospitalised with COVID-19 (n=68). Of those, 48 were in the ICU (on mechanical ventilation) and 20 were outside the ICU (on supplemental oxygen), and an additional cohort of 13 non-hospitalised, asymptomatic patients were used as a comparator reference control group. There were no statistically significant differences in age or comorbid conditions between the ICU and non-ICU patients.

As anticipated, D-dimer and thrombin-antithrombin levels were high in both the ICU and non-ICU populations were increased, but levels were significantly higher (P<0.001) among the ICU patients. Endogenous anticoagulants (antithrombin and proteins C and S) and fibrinolytic enzymes (α 2-antiplasmin) were preserved, verifying that CAC is distinct from disseminated intravascular coagulation. Classic fibrinolysis did not occur, as plasminogen activation inhibitor 1 (PAI-1) was high in both ICU and non-ICU patients, and lysis-30 was normal in nearly all ICU patients (96%). Von Willebrand factor antigen and activity levels and factor VIII levels were markedly elevated in non-ICU and ICU patients, but they were significantly higher (mean 565 ± 199% in ICU patients vs 278 ± 133% in non-ICU patients; P<0.0001) in the ICU cohort. Soluble P-selectin was also higher in the ICU patients (15.9 ± 4.8 ng/mL vs 11.2 ± 3.1 ng/mL; P=0.0014). Mortality significantly correlated with Von Willebrand factor antigen (R=0.38; P=0.0022) and soluble thrombomodulin (R=0.38; P=0.0078) in all patients. Furthermore, soluble thrombomodulin concentrations >3.26 ng/mL were associated with lower rates of hospital discharge (P=0.0050) and lower likelihood of survival (HR 5.9; 95% CI 1.9-18.4; P=0.0087).

In conclusion, markers of endothelial damage suggest pathophysiological aetiology and can be used to predict disease outcomes. Early identification of endotheliopathy, with consequent management, may improve outcomes in COVID-19.

 

1. Goshua G, et al. Endotheliopathy is essential in COVID-19 associated coagulopathy. EHA25 Virtual, 11-21 June 2020, Abstract LB2605.

Posted on 28 August 20208 April 2024