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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
PMID32619411
show 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.