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10.1016/S2352-3026(20)30216-7

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32619411!7326446!32619411
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suck abstract from ncbi


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pmid32619411      Lancet+Haematol 2020 ; 7 (8): e575-e582
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  • Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study #MMPMID32619411
  • Goshua G; Pine AB; Meizlish ML; Chang CH; Zhang H; Bahel P; Baluha A; Bar N; Bona RD; Burns AJ; Dela Cruz CS; Dumont A; Halene S; Hwa J; Koff J; Menninger H; Neparidze N; Price C; Siner JM; Tormey C; Rinder HM; Chun HJ; Lee AI
  • Lancet Haematol 2020[Aug]; 7 (8): e575-e582 PMID32619411show ga
  • 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.
  • |Adult[MESH]
  • |Aged[MESH]
  • |Aged, 80 and over[MESH]
  • |Betacoronavirus/*pathogenicity[MESH]
  • |Biomarkers/metabolism[MESH]
  • |Blood Coagulation Disorders/etiology/metabolism/*pathology[MESH]
  • |COVID-19[MESH]
  • |Coronavirus Infections/*complications/virology[MESH]
  • |Critical Illness[MESH]
  • |Cross-Sectional Studies[MESH]
  • |Endothelium, Vascular/metabolism/*pathology[MESH]
  • |Female[MESH]
  • |Follow-Up Studies[MESH]
  • |Humans[MESH]
  • |Intensive Care Units[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Pandemics[MESH]
  • |Pneumonia, Viral/*complications/virology[MESH]
  • |Prognosis[MESH]
  • |SARS-CoV-2[MESH]
  • |Vascular Diseases/etiology/metabolism/*pathology[MESH]


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