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Lancet Haematol . Endotheliopathy in COVID-19-associated Coagulopathy: Evidence From a Single-Centre, Cross-Sectional Study

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  • Lancet Haematol . Endotheliopathy in COVID-19-associated Coagulopathy: Evidence From a Single-Centre, Cross-Sectional Study


    Lancet Haematol


    . 2020 Jun 30;S2352-3026(20)30216-7.
    doi: 10.1016/S2352-3026(20)30216-7. Online ahead of print.
    Endotheliopathy in COVID-19-associated Coagulopathy: Evidence From a Single-Centre, Cross-Sectional Study


    George Goshua 1 , Alexander B Pine 1 , Matthew L Meizlish 2 , C-Hong Chang 3 , Hanming Zhang 3 , Parveen Bahel 4 , Audrey Baluha 5 , Noffar Bar 1 , Robert D Bona 1 , Adrienne J Burns 5 , Charles S Dela Cruz 6 , Anne Dumont 5 , Stephanie Halene 1 , John Hwa 3 , Jonathan Koff 6 , Hope Menninger 5 , Natalia Neparidze 1 , Christina Price 7 , Jonathan M Siner 6 , Christopher Tormey 4 , Henry M Rinder 4 , Hyung J Chun 3 , Alfred I Lee 8



    Affiliations

    Abstract

    Background: An important feature of severe acute respiratory syndrome coronavirus 2 pathogenesis is COVID-19-associated coagulopathy, characterised by increased thrombotic and microvascular complications. Previous studies have suggested a role for endothelial cell injury in COVID-19-associated coagulopathy. To determine whether endotheliopathy is involved in COVID-19-associated coagulopathy pathogenesis, we assessed markers of endothelial cell and platelet activation in critically and non-critically ill patients admitted to the hospital with COVID-19.
    Methods: In this single-centre cross-sectional study, hospitalised adult (≥18 years) patients with laboratory-confirmed COVID-19 were identified in the medical intensive care unit (ICU) or a specialised non-ICU COVID-19 floor in our hospital. Asymptomatic, non-hospitalised controls were recruited as a comparator group for biomarkers that did not have a reference range. We assessed markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes. We compared the level of each marker in ICU patients, non-ICU patients, and controls, where applicable. We assessed correlations between these laboratory results with clinical outcomes, including hospital discharge and mortality. Kaplan-Meier analysis was used to further explore the association between biochemical markers and survival.
    Findings: 68 patients with COVID-19 were included in the study from April 13 to April 24, 2020, including 48 ICU and 20 non-ICU patients, as well as 13 non-hospitalised, asymptomatic controls. Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen (mean 565% [SD 199] in ICU patients vs 278% [133] in non-ICU patients; p<0?0001) and soluble P-selectin (15?9 ng/mL [4?8] vs 11?2 ng/mL [3?1]; p=0?0014). VWF antigen concentrations were also elevated above the normal range in 16 (80%) of 20 non-ICU patients. We found mortality to be significantly correlated with VWF antigen (r = 0?38; p=0?0022) and soluble thrombomodulin (r = 0?38; p=0?0078) among all patients. In all patients, soluble thrombomodulin concentrations greater than 3?26 ng/mL were associated with lower rates of hospital discharge (22 [88%] of 25 patients with low concentrations vs 13 [52%] of 25 patients with high concentrations; p=0?0050) and lower likelihood of survival on Kaplan-Meier analysis (hazard ratio 5?9, 95% CI 1?9-18?4; p=0?0087).
    Interpretation: Our findings show that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death. Early identification of endotheliopathy and strategies to mitigate its progression might improve outcomes in COVID-19.
    Funding: This work was supported by a gift donation from Jack Levin to the Benign Hematology programme at Yale, and the National Institutes of Health.


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