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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308437

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has been associated with coagulation disorders, in particular high levels of D-dimers, and increased frequency of venous thromboembolism (VTE). We explore the association between D-dimers at admission and in-hospital mortality in hospitalized COVID-19 patients with or without symptomatic VTE. Methods: : From February 26 to April 20, 2020, D-dimer level at admission and outcomes of patients hospitalized for COVID-19 in medical wards (in-hospital mortality or VTE) were retrospectively analyzed in a multicenter study in 24 French hospitals. Results: : Among 2878 patients enrolled in the study, 1154 (40.9%) patients had D-dimer measurement at admission. A receiver operating characteristic (ROC) curve analysis identified D-dimer level above 1128 ng/mL as the optimum cutoff value to predict in-hospital mortality (Area Under the Curve of 64.9% (95% CI 0.60–0.69) with a sensitivity of 71.1% (95% CI 0.62–0.78) and a specificity of 55.6% (95% CI 0.52–0.58) that not differ in the subgroup of patients with VTE during hospitalization. Among 609 (52.8%) patients with D-dimers level < 1128 ng/mL at admission, only 35 (5.7%) deaths occurred during hospitalization. After adjustment, in a cox proportional hazard and logistic regression models, D-dimers above 1128 ng/mL at admission were also associated to a worth prognosis with a OR of 3.07 (95% CI 2.05–4.69, p < 0.001) and an unadjusted hazard ratio of 2.11 (95%CI 1.31–3.4, p < 0.01). Conclusions: : D-dimer level over 1128 ng/mL is a relevant predictive factor for in-hospital mortality in COVID-19 hospitalized patients in medical ward, regardless the occurrence of VTE during hospitalization.

2.
Arthritis Rheumatol ; 73(11): 1976-1985, 2021 11.
Article in English | MEDLINE | ID: covidwho-1432359

ABSTRACT

OBJECTIVE: The clinical relevance of antiphospholipid antibodies (aPLs) in COVID-19 is controversial. This study was undertaken to investigate the prevalence and prognostic value of conventional and nonconventional aPLs in patients with COVID-19. METHODS: This was a multicenter, prospective observational study in a French cohort of patients hospitalized with suspected COVID-19. RESULTS: Two hundred forty-nine patients were hospitalized with suspected COVID-19, in whom COVID-19 was confirmed in 154 and not confirmed in 95. We found a significant increase in lupus anticoagulant (LAC) positivity among patients with COVID-19 compared to patients without COVID-19 (60.9% versus 23.7%; P < 0.001), while prevalence of conventional aPLs (IgG and IgM anti-ß2 -glycoprotein I and IgG and IgM anticardiolipin isotypes) and nonconventional aPLs (IgA isotype of anticardiolipin, IgA isotype of anti-ß2 -glycoprotein I, IgG and IgM isotypes of anti-phosphatidylserine/prothrombin, and IgG and IgM isotypes of antiprothrombin) was low in both groups. Patients with COVID-19 who were positive for LAC, as compared to patients with COVID-19 who were negative for LAC, had higher levels of fibrinogen (median 6.0 gm/liter [interquartile range 5.0-7.0] versus 5.3 gm/liter [interquartile range 4.3-6.4]; P = 0.028) and C-reactive protein (CRP) (median 115.5 mg/liter [interquartile range 66.0-204.8] versus 91.8 mg/liter [interquartile range 27.0-155.1]; P = 0.019). Univariate analysis did not show any association between LAC positivity and higher risks of venous thromboembolism (VTE) (odds ratio 1.02 [95% confidence interval 0.44-2.43], P = 0.95) or in-hospital mortality (odds ratio 1.80 [95% confidence interval 0.70-5.05], P = 0.24). With and without adjustment for CRP level, age, and sex, Kaplan-Meier survival curves according to LAC positivity confirmed the absence of an association with VTE or in-hospital mortality (unadjusted P = 0.64 and P = 0.26, respectively; adjusted hazard ratio 1.13 [95% confidence interval 0.48-2.60] and 1.80 [95% confidence interval 0.67-5.01], respectively). CONCLUSION: Patients with COVID-19 have an increased prevalence of LAC positivity associated with biologic markers of inflammation. However, LAC positivity at the time of hospital admission is not associated with VTE risk and/or in-hospital mortality.


Subject(s)
COVID-19/complications , Lupus Coagulation Inhibitor/blood , Venous Thromboembolism/etiology , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/mortality , Female , Hospital Mortality , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Risk Factors , Survival Rate , Venous Thromboembolism/blood
3.
J Am Heart Assoc ; 10(8): e018624, 2021 04 20.
Article in English | MEDLINE | ID: covidwho-1189969

ABSTRACT

Background Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with thrombotic outcomes with coagulation and endothelial disorders. Based on that, several anticoagulation guidelines have been proposed. We aimed to determine whether anticoagulation therapy modifies the risk of developing severe COVID-19. Methods and Results Patients with COVID-19 initially admitted in medical wards of 24 French hospitals were included prospectively from February 26 to April 20, 2020. We used a Poisson regression model, Cox proportional hazard model, and matched propensity score to assess the effect of anticoagulation on outcomes (intensive care unit admission or in-hospital mortality). The study enrolled 2878 patients with COVID-19, among whom 382 (13.2%) were treated with oral anticoagulation therapy before hospitalization. After adjustment, anticoagulation therapy before hospitalization was associated with a better prognosis with an adjusted hazard ratio of 0.70 (95% CI, 0.55-0.88). Analyses performed using propensity score matching confirmed that anticoagulation therapy before hospitalization was associated with a better prognosis, with an adjusted hazard ratio of 0.43 (95% CI, 0.29-0.63) for intensive care unit admission and adjusted hazard ratio of 0.76 (95% CI, 0.61-0.98) for composite criteria intensive care unit admission or death. In contrast, therapeutic or prophylactic low- or high-dose anticoagulation started during hospitalization were not associated with any of the outcomes. Conclusions Anticoagulation therapy used before hospitalization in medical wards was associated with a better prognosis in contrast with anticoagulation initiated during hospitalization. Anticoagulation therapy introduced in early disease could better prevent COVID-19-associated coagulopathy and endotheliopathy, and lead to a better prognosis.


Subject(s)
Anticoagulants/therapeutic use , COVID-19 , Intensive Care Units/statistics & numerical data , Thromboembolism/prevention & control , Blood Coagulation/drug effects , COVID-19/blood , COVID-19/mortality , COVID-19/therapy , Early Medical Intervention/methods , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiopathology , Female , France/epidemiology , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Prognosis , Protective Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Thromboembolism/epidemiology
4.
Arch Cardiovasc Dis ; 114(5): 381-393, 2021 May.
Article in English | MEDLINE | ID: covidwho-1179190

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been associated with coagulation disorders, in particular high concentrations of D-dimer, and increased frequency of venous thromboembolism. AIM: To explore the association between D-dimer at admission and in-hospital mortality in patients hospitalised for COVID-19, with or without symptomatic venous thromboembolism. METHODS: From 26 February to 20 April 2020, D-dimer concentration at admission and outcomes (in-hospital mortality and venous thromboembolism) of patients hospitalised for COVID-19 in medical wards were retrospectively analysed in a multicenter study in 24 French hospitals. RESULTS: Among 2878 patients enrolled in the study, 1154 (40.1%) patients had D-dimer measurement at admission. Receiver operating characteristic curve analysis identified a D-dimer concentration>1128ng/mL as the best cut-off value for in-hospital mortality (area under the curve 64.9%, 95% confidence interval [CI] 60-69), with a sensitivity of 71.1% (95% CI 62-78) and a specificity of 55.6% (95% CI 52-58), which did not differ in the subgroup of patients with venous thromboembolism during hospitalisation. Among 545 (47.2%) patients with D-dimer concentration>1128ng/mL at admission, 86 (15.8%) deaths occurred during hospitalisation. After adjustment, in Cox proportional hazards and logistic regression models, D-dimer concentration>1128ng/mL at admission was also associated with a worse prognosis, with an odds ratio of 3.07 (95% CI 2.05-4.69; P<0.001) and an adjusted hazard ratio of 2.11 (95% CI 1.31-3.4; P<0.01). CONCLUSIONS: D-dimer concentration>1128ng/mL is a relevant predictive factor for in-hospital mortality in patients hospitalised for COVID-19 in a medical ward, regardless of the occurrence of venous thromboembolism during hospitalisation.


Subject(s)
COVID-19/blood , Fibrin Fibrinogen Degradation Products/analysis , Thrombophilia/blood , Adolescent , Adult , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Area Under Curve , COVID-19/complications , COVID-19/mortality , COVID-19 Nucleic Acid Testing , Child , Child, Preschool , Electronic Health Records , France/epidemiology , Hospital Mortality , Humans , Infant , Infant, Newborn , Kaplan-Meier Estimate , Male , Middle Aged , Patient Admission , Patients' Rooms , Prognosis , Proportional Hazards Models , ROC Curve , Retrospective Studies , Thrombophilia/drug therapy , Thrombophilia/etiology , Venous Thromboembolism/epidemiology , Young Adult
5.
J Thromb Haemost ; 19(7): 1823-1830, 2021 07.
Article in English | MEDLINE | ID: covidwho-1172713

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with vascular inflammation and endothelial injury. OBJECTIVES: To correlate circulating angiogenic markers vascular endothelial growth factor A (VEGF-A), placental growth factor (PlGF), and fibroblast growth factor 2 (FGF-2) to in-hospital mortality in COVID-19 adult patients. METHODS: Consecutive ambulatory and hospitalized patients with COVID-19 infection were enrolled. VEGF-A, PlGF, and FGF-2 were measured in each patient ≤48 h following admission. RESULTS: The study enrolled 237 patients with suspected COVID-19: 208 patients had a positive diagnostic for COVID-19, of whom 23 were mild outpatients and 185 patients hospitalized after admission. Levels of VEGF-A, PlGF, and FGF-2 significantly increase with the severity of the disease (P < .001). Using a logistic regression model, we found a significant association between the increase of FGF-2 or PlGF and mortality (odds ratio [OR] 1.11, 95% confidence interval [CI; 1.07-1.16], P < .001 for FGF-2 and OR 1.07 95% CI [1.04-1.10], P < .001 for PlGF) while no association were found for VEGF-A levels. Receiver operating characteristic curve analysis was performed and we identified PlGF above 30 pg/ml as the best predictor of in-hospital mortality in COVID-19 patients. Survival analysis for PlGF confirmed its interest for in-hospital mortality prediction, by using a Kaplan-Meier survival curve (P = .001) and a Cox proportional hazard model adjusted to age, body mass index, D-dimer, and C-reactive protein (3.23 95% CI [1.29-8.11], P = .001). CONCLUSION: Angiogenic factor PlGF is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that PlGF blocking strategies could be a new interesting therapeutic approach in COVID-19.


Subject(s)
COVID-19 , Vascular Endothelial Growth Factor A , Adult , Biomarkers , Female , Hospital Mortality , Humans , Placenta Growth Factor , SARS-CoV-2
6.
Angiogenesis ; 24(3): 505-517, 2021 08.
Article in English | MEDLINE | ID: covidwho-1032491

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with endotheliitis and microthrombosis. OBJECTIVES: To correlate endothelial dysfunction to in-hospital mortality in a bi-centric cohort of COVID-19 adult patients. METHODS: Consecutive ambulatory and hospitalized patients with laboratory-confirmed COVID-19 were enrolled. A panel of endothelial biomarkers and von Willebrand factor (VWF) multimers were measured in each patient ≤ 48 h following admission. RESULTS: Study enrolled 208 COVID-19 patients of whom 23 were mild outpatients and 189 patients hospitalized after admission. Most of endothelial biomarkers tested were found increased in the 89 critical patients transferred to intensive care unit. However, only von Willebrand factor antigen (VWF:Ag) scaled according to clinical severity, with levels significantly higher in critical patients (median 507%, IQR 428-596) compared to non-critical patients (288%, 230-350, p < 0.0001) or COVID-19 outpatients (144%, 133-198, p = 0.007). Moreover, VWF high molecular weight multimers (HMWM) were significantly higher in critical patients (median ratio 1.18, IQR 0.86-1.09) compared to non-critical patients (0.96, 1.04-1.39, p < 0.001). Among all endothelial biomarkers measured, ROC curve analysis identified a VWF:Ag cut-off of 423% as the best predictor for in-hospital mortality. The accuracy of VWF:Ag was further confirmed in a Kaplan-Meier estimator analysis and a Cox proportional Hazard model adjusted on age, BMI, C-reactive protein and D-dimer levels. CONCLUSION: VWF:Ag is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that VWF, including excess of HMWM forms, drives microthrombosis in COVID-19.


Subject(s)
COVID-19/blood , COVID-19/mortality , Pandemics , SARS-CoV-2 , von Willebrand Factor/metabolism , Adult , Aged , Biomarkers/blood , Biomarkers/chemistry , COVID-19/physiopathology , Cross-Sectional Studies , Endothelium, Vascular/physiopathology , Female , Hospital Mortality , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Molecular Weight , Paris/epidemiology , Proportional Hazards Models , Protein Multimerization , Severity of Illness Index , Thrombosis/blood , Thrombosis/etiology , von Willebrand Factor/chemistry
7.
Arterioscler Thromb Vasc Biol ; 41(1): 415-429, 2021 01.
Article in English | MEDLINE | ID: covidwho-1027162

ABSTRACT

OBJECTIVE: The study's aim was to analyze the capacity of human valve interstitial cells (VICs) to participate in aortic valve angiogenesis. Approach and Results: VICs were isolated from human aortic valves obtained after surgery for calcific aortic valve disease and from normal aortic valves unsuitable for grafting (control VICs). We examined VIC in vitro and in vivo potential to differentiate in endothelial and perivascular lineages. VIC paracrine effect was also examined on human endothelial colony-forming cells. A pathological VIC (VICp) mesenchymal-like phenotype was confirmed by CD90+/CD73+/CD44+ expression and multipotent-like differentiation ability. When VICp were cocultured with endothelial colony-forming cells, they formed microvessels by differentiating into perivascular cells both in vivo and in vitro. VICp and control VIC conditioned media were compared using serial ELISA regarding quantification of endothelial and angiogenic factors. Higher expression of VEGF (vascular endothelial growth factor)-A was observed at the protein level in VICp-conditioned media and confirmed at the mRNA level in VICp compared with control VIC. Conditioned media from VICp induced in vitro a significant increase in endothelial colony-forming cell proliferation, migration, and sprouting compared with conditioned media from control VIC. These effects were inhibited by blocking VEGF-A with blocking antibody or siRNA approach, confirming VICp involvement in angiogenesis by a VEGF-A dependent mechanism. CONCLUSIONS: We provide here the first proof of an angiogenic potential of human VICs isolated from patients with calcific aortic valve disease. These results point to a novel function of VICp in valve vascularization during calcific aortic valve disease, with a perivascular differentiation ability and a VEGF-A paracrine effect. Targeting perivascular differentiation and VEGF-A to slow calcific aortic valve disease progression warrants further investigation.


Subject(s)
Aortic Valve Stenosis/metabolism , Aortic Valve/metabolism , Aortic Valve/pathology , Calcinosis/metabolism , Cell Differentiation , Cell Lineage , Endothelial Progenitor Cells/metabolism , Neovascularization, Pathologic , Vascular Endothelial Growth Factor A/metabolism , Adult , Aged , Aged, 80 and over , Animals , Aortic Valve Stenosis/pathology , Calcinosis/pathology , Case-Control Studies , Cells, Cultured , Coculture Techniques , Endothelial Progenitor Cells/pathology , Endothelial Progenitor Cells/transplantation , Female , Humans , Male , Mice, Nude , Middle Aged , Osteogenesis , Paracrine Communication , Phenotype , Signal Transduction , Vascular Endothelial Growth Factor A/genetics
8.
Oncoimmunology ; 9(1): 1857112, 2020 12 08.
Article in English | MEDLINE | ID: covidwho-990263

ABSTRACT

Formyl peptide receptor 1 (FPR1) is a pattern-recognition receptor that detects bacterial as well as endogenous danger-associated molecular patterns to trigger innate immune responses by myeloid cells. A single nucleotide polymorphism, rs867228 (allelic frequency 19-20%), in the gene coding for FPR1 accelerates the manifestation of multiple carcinomas, likely due to reduced anticancer immunosurveillance secondary to a defect in antigen presentation by dendritic cells. Another polymorphism in FPR1, rs5030880 (allelic frequency 12-13%), has been involved in the resistance to plague, correlating with the fact that FPR1 is the receptor for Yersinia pestis. Driven by the reported preclinical effects of FPR1 on lung inflammation and fibrosis, we investigated whether rs867228 or rs5030880 would affect the severity of coronavirus disease-19 (COVID-19). Data obtained on patients from two different hospitals in Paris refute the hypothesis that rs867228 or rs5030880 would affect the severity of COVID-19.


Subject(s)
COVID-19/genetics , COVID-19/virology , Neoplasms/genetics , Plague/genetics , Receptors, Formyl Peptide/genetics , SARS-CoV-2/isolation & purification , COVID-19/epidemiology , COVID-19/pathology , Female , Humans , Immunity, Innate , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/pathology , Neoplasms/virology , Pandemics , Paris/epidemiology , Plague/microbiology , Plague/pathology , Polymorphism, Single Nucleotide , SARS-CoV-2/genetics
9.
Front Med (Lausanne) ; 7: 586307, 2020.
Article in English | MEDLINE | ID: covidwho-954333

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has been associated with cardiovascular complications and coagulation disorders. Objectives: To explore clinical and biological parameters of COVID-19 patients with hospitalization criteria that could predict referral to intensive care unit (ICU). Methods: Analyzing the clinical and biological profiles of COVID-19 patients at admission. Results: Among 99 consecutive patients that fulfilled criteria for hospitalization, 48 were hospitalized in the medicine department, 21 were first admitted to the medicine ward department and referred later to ICU, and 30 were directly admitted to ICU from the emergency department. At admission, patients requiring ICU were more likely to have lymphopenia, decreased SpO2, a D-dimer level above 1,000 ng/mL, and a higher high-sensitivity cardiac troponin (Hs-cTnI) level. A receiver operating characteristic curve analysis identified Hs-cTnI above 9.75 pg/mL as the best predictive criteria for ICU referral [area under the curve (AUC), 86.4; 95% CI, 76.6-96.2]. This cutoff for Hs-cTnI was confirmed in univariate [odds ratio (OR), 22.8; 95% CI, 6.0-116.2] and multivariate analysis after adjustment for D-dimer level (adjusted OR, 20.85; 95% CI, 4.76-128.4). Transthoracic echocardiography parameters subsequently measured in 72 patients showed an increased right ventricular (RV) afterload correlated with Hs-cTnI (r = 0.42, p = 0.010) and D-dimer (r = 0.18, p = 0.047). Conclusion: Hs-cTnI appears to be the best relevant predictive factor for referring COVID-19 patients to ICU. This result associated with the correlation of D-dimer with RV dilatation probably reflects a myocardial injury due to an increased RV wall tension. This reinforces the hypothesis of a COVID-19-associated microvascular thrombosis inducing a higher RV afterload.

10.
Stem Cell Rev Rep ; 17(2): 639-651, 2021 04.
Article in English | MEDLINE | ID: covidwho-932630

ABSTRACT

Endothelial progenitor cells (EPCs) are involved in vasculogenesis and cardiovascular diseases. However, the phenotype of circulating EPCs remains elusive but they are more often described as CD34+KDR+. The aim of the study was to extensively characterize circulating potential vasculogenic stem cell candidates in two populations of patients with cardiovascular disease by powerful multidimensional single cell complementary cytometric approaches (mass, imaging and flow). We identified cellular candidates in one patient before and after bioprosthetic total artificial heart implantation and results were confirmed in healthy peripheral and cord blood by mass cytometry. We also quantified cellular candidates in 10 patients with different COVID-19 severity. Both C-TAH implantation and COVID-19 at critical stage induce a redistribution of circulating CD34+ and CD19+ sub-populations in peripheral blood. After C-TAH implantation, circulating CD34+ progenitor cells expressed c-Kit stem marker while specific subsets CD34+CD133-/+CD45-/dimc-Kit+KDR- were mobilized. KDR was only expressed by CD19+ B-lymphocytes and CD14+ monocytes subpopulations in circulation. We confirmed by mass cytometry this KDR expression on CD19+ in healthy peripheral and cord blood, also with a VE-cadherin expression, confirming absence of endothelial lineage marker on CD34+ subtypes. In COVID-19, a significant mobilization of CD34+c-Kit+KDR- cells was observed between moderate and critical COVID-19 patients regardless CD133 or CD45 expression. In order to better evaluate EPC phenotype, we performed imaging flow cytometry measurements of immature CD34+KDR+ cells in cord blood and showed that, after elimination of non-circular events, those cells were all CD19+. During COVID-19, a significant mobilization of CD19+KDR+ per million of CD45+ cells was observed between moderate and critical COVID-19 patients regardless of CD34 expression. CD34+c-Kit+ cells are mobilized in both cardiovascular disease described here. KDR cells in peripheral blood are CD19 positive cells and are not classic vasculogenic stem and/or progenitor cells. A better evaluation of c-Kit and KDR expressing cells will lead to the redefinition of circulating endothelial progenitors.Graphical abstract Central illustration figure. Multidimensional proteomic approach of endothelial progenitors demonstrate expression of KDR restricted to CD19 cells. Endothelial progenitor cells (EPCs) are involved in cardiovascular diseases, however their phenotype remains elusive. We elucidated here EPCs phenotype by a deep characterization by multidimensional single cell complementary cytometric approaches after Bioprosthetic total artificial heart implantation and during COVID-19. We showed a redistribution of circulating CD34+ and CD19+ sub-populations in both situations. None of the immature cell population expresses KDR. Mobilized CD34+ expressed c-Kit. Imaging flow cytometry demonstrated that CD34+KDR+ cells, after elimination of non-circular events, are all CD19+. Our results suggest a new definition of circulating EPCs and emphasize involvement of CD19 cells in cardiovascular disease.


Subject(s)
Antigens, CD19/metabolism , COVID-19/metabolism , Endothelial Progenitor Cells/metabolism , Gene Expression Regulation , Heart, Artificial , SARS-CoV-2/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolism , Endothelial Progenitor Cells/pathology , Female , Humans , Male , Middle Aged , Proteomics
11.
J Thromb Haemost ; 18(9): 2391-2399, 2020 09.
Article in English | MEDLINE | ID: covidwho-607342

ABSTRACT

BACKGROUND: Coronavirus disease-2019 (COVID-19) has been associated with cardiovascular complications and coagulation disorders. OBJECTIVES: To explore the coagulopathy and endothelial dysfunction in COVID-19 patients. METHODS: The study analyzed clinical and biological profiles of patients with suspected COVID-19 infection at admission, including hemostasis tests and quantification of circulating endothelial cells (CECs). RESULTS: Among 96 consecutive COVID-19-suspected patients fulfilling criteria for hospitalization, 66 were tested positive for SARS-CoV-2. COVID-19-positive patients were more likely to present with fever (P = .02), cough (P = .03), and pneumonia at computed tomography (CT) scan (P = .002) at admission. Prevalence of D-dimer >500 ng/mL was higher in COVID-19-positive patients (74.2% versus 43.3%; P = .007). No sign of disseminated intravascular coagulation were identified. Adding D-dimers >500 ng/mL to gender and pneumonia at CT scan in receiver operating characteristic curve analysis significantly increased area under the curve for COVID-19 diagnosis. COVID-19-positive patients had significantly more CECs at admission (P = .008) than COVID-19-negative ones. COVID-19-positive patients treated with curative anticoagulant prior to admission had fewer CECs (P = .02) than those without. Interestingly, patients treated with curative anticoagulation and angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers had even fewer CECs (P = .007). CONCLUSION: Curative anticoagulation could prevent COVID-19-associated coagulopathy and endothelial lesion.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , COVID-19/therapy , Aged , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Blood Coagulation , Blood Coagulation Disorders/complications , Blood Coagulation Disorders/drug therapy , Cardiovascular Diseases/complications , Endothelial Cells/metabolism , Female , Fibrin Fibrinogen Degradation Products/analysis , Hemostasis , Hospitalization , Humans , Male , Middle Aged , Patient Admission , Pneumonia, Viral/diagnostic imaging , Prevalence , Prospective Studies , ROC Curve , Tomography, X-Ray Computed
12.
Angiogenesis ; 23(4): 611-620, 2020 11.
Article in English | MEDLINE | ID: covidwho-377964

ABSTRACT

BACKGROUND: Coronavirus disease-2019 (COVID-19), a respiratory disease has been associated with ischemic complications, coagulation disorders, and an endotheliitis. OBJECTIVES: To explore endothelial damage and activation-related biomarkers in COVID-19 patients with criteria of hospitalization for referral to intensive care unit (ICU) and/or respiratory worsening. METHODS: Analysis of endothelial and angiogenic soluble markers in plasma from patients at admission. RESULTS: Study enrolled 40 consecutive COVID-19 patients admitted to emergency department that fulfilled criteria for hospitalization. Half of them were admitted in conventional wards without any ICU transfer during hospitalization; whereas the 20 others were directly transferred to ICU. Patients transferred in ICU were more likely to have lymphopenia, decreased SpO2 and increased D-dimer, CRP and creatinine levels. In those patients, soluble E-selectin and angiopoietin-2 were significantly increased (p value at 0.009 and 0.003, respectively). Increase in SELE gene expression (gene coding for E-selectin protein) was confirmed in an independent cohort of 32 patients using a whole blood gene expression profile analysis. In plasma, we found a strong association between angiopoetin-2 and CRP, creatinine and D-dimers (with p value at 0.001, 0.001 and 0.003, respectively). ROC curve analysis identified an Angiopoietin-2 cut-off of 5000 pg/mL as the best predictor for ICU outcome (Se = 80.1%, Sp = 70%, PPV = 72.7%, NPV = 77%), further confirmed in multivariate analysis after adjustment for creatinine, CRP or D-dimers. CONCLUSION: Angiopoietin-2 is a relevant predictive factor for ICU direct admission in COVID-19 patients. This result showing an endothelial activation reinforces the hypothesis of a COVID-19-associated microvascular dysfunction.


Subject(s)
Angiopoietin-2/blood , Coronavirus Infections/blood , Coronavirus Infections/therapy , Endothelium, Vascular/metabolism , Intensive Care Units , Pneumonia, Viral/blood , Pneumonia, Viral/therapy , Aged , Betacoronavirus , Biomarkers/blood , COVID-19 , Critical Care/methods , E-Selectin/blood , Female , Gene Expression Profiling , Hospitalization , Humans , Male , Middle Aged , Pandemics , Patient Admission , Prospective Studies , Respiration, Artificial , SARS-CoV-2
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