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3.
Thromb Haemost ; 2022 Feb 10.
Article in English | MEDLINE | ID: covidwho-1684157

ABSTRACT

INTRODUCTION: D-dimer measurement is a safe tool to exclude pulmonary embolism (PE) but its specificity decreases in COVID-19. Our aim was to derive a new algorithm with specific D-dimer threshold in COVID-19 patients. METHODS: We conducted a French multicenter, retrospective cohort study among 774 COVID-19 patients with suspected PE. D-dimer threshold adjusted to computed tomography (CT) extent of lung damage was derived in a patient set (n=337), and its safety assessed in an independent validation set (n=337). RESULTS: According to ROC curves, in the derivation set D-dimer safely excluded PE, with one false negative when using a 900 ng/mL threshold when lung damage extent was <50% and 1700 ng/mL when lung damage extent was ≥50%. In the derivation set, the algorithm sensitivity was 98.2% (95% CI: 94.7-100.0) and its specificity 28.4% (95% CI: 24.1-32.3). The negative likelihood ratio (NLR) was 0.06 (95% CI: 0.01-0.44) and the area under the curve (AUC) was 0.63 (95% CI: 0.60-0.67). In the validation set, sensitivity and specificity were 96.7% (95% CI: 88.7-99.6) and 39.2% (95% CI: 32.2-46.1), respectively. The NLR was 0.08 (95% CI; 0.02-0.33) and the AUC did not differed from that of the derivation set (0.68 ,95% CI: 0.64-0.72, P = 0.097). Using the Co-LEAD algorithm, 76/250 (30.4%) COVID-19 patients with suspected PE could have been managed without CT pulmonary angiography (CTPA). CONCLUSION: The Co-LEAD algorithm safely excludes PE, and allows reducing the use of CTPA among COVID-19 patients. Further prospective studies are necessary to validate this strategy.

6.
TH open : companion journal to thrombosis and haemostasis ; 6(1):e21-e25, 2021.
Article in English | EuropePMC | ID: covidwho-1652310
7.
The Journal of allergy and clinical immunology ; 2021.
Article in English | EuropePMC | ID: covidwho-1519110

ABSTRACT

Background Severe coronavirus disease 2019 (COVID-19) is characterized by impaired type I interferon activity and a state of hyperinflammation leading to acute respiratory distress syndrome. The complement system has recently emerged as a key player in triggering and maintaining the inflammatory state, but the role of this molecular cascade in severe COVID-19 is still poorly characterized. Objective We aimed at assessing the contribution of complement pathways at both protein and transcriptomic levels. Methods To this end, we systematically assessed RNA levels of 28 complement genes in circulating whole blood of COVID-19 patients and healthy controls, including genes of the alternative pathway, for which data remain scarce. Results We found differential expression of genes involved in the complement system, yet with various expression patterns: while patients displaying moderate disease had elevated expression of classical pathway genes, severe disease was associated with increased lectin and alternative pathway activation, which correlated with inflammation and coagulopathy markers. Additionally, properdin, a pivotal positive regulator of the alternative pathway, showed high RNA expression but was found at low protein concentrations in severe and critical patients, suggesting its deposition at the sites of complement activation. Notably, low properdin levels were significantly associated with the use of mechanical ventilation (AUC = 0.82, p = 0.002). Conclusion This study sheds light on the role of the alternative pathway in severe COVID-19 and provides additional rationale for the testing of drugs inhibiting the alternative pathway of the complement system. We show that activation of the alternative complement pathway characterizes COVID-19 severity. Specifically, low properdin levels were associated with use of mechanical ventilation. This work provides a rationale for the specific inhibition of the alternative complement pathway.

8.
Front Med (Lausanne) ; 8: 747527, 2021.
Article in English | MEDLINE | ID: covidwho-1497093

ABSTRACT

Background: Microthrombosis and large-vessel thrombosis are the main triggers of COVID-19 worsening. The optimal anticoagulant regimen in COVID-19 patients hospitalized in medical wards remains unknown. Objectives: To evaluate the effects of intermediate-dose vs. standard-dose prophylactic anticoagulation (AC) among patients with COVID-19 hospitalized in medical wards. Methods and results: We used a large French multicentric retrospective study enrolling 2,878 COVID-19 patients hospitalized in medical wards. After exclusion of patients who had an AC treatment before hospitalization, we generated a propensity-score-matched cohort of patients who were treated with intermediate-dose or standard-dose prophylactic AC between February 26 and April 20, 2020 (intermediate-dose, n = 261; standard-dose prophylactic anticoagulation, n = 763). The primary outcome of the study was in-hospital mortality; this occurred in 23 of 261 (8.8%) patients in the intermediate-dose group and 74 of 783 (9.4%) patients in the standard-dose prophylactic AC group (p = 0.85); while time to death was also the same in both the treatment groups (11.5 and 11.6 days, respectively, p = 0.17). We did not observe any difference regarding venous and arterial thrombotic events between the intermediate dose and standard dose, respectively (venous thrombotic events: 2.3 vs. 2.4%, p=0.99; arterial thrombotic events: 2.7 vs. 1.2%, p = 0.25). The 30-day Kaplan-Meier curves for in-hospital mortality demonstrate no statistically significant difference in in-hospital mortality (HR: 0.99 (0.63-1.60); p = 0.99). Moreover, we found that no particular subgroup was associated with a significant reduction in in-hospital mortality. Conclusion: Among COVID-19 patients hospitalized in medical wards, intermediate-dose prophylactic AC compared with standard-dose prophylactic AC did not result in a significant difference in in-hospital mortality.

9.
Crit Care Med ; 49(11): e1151-e1156, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1467423

ABSTRACT

TRIAL REGISTRATION: NCT04420468. OBJECTIVES: Severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children is frequently associated with shock; endothelial involvement may be one of the underlying mechanisms. We sought to describe endothelial dysfunction during multisystem inflammatory syndrome in children with shock and then assess the relationship between the degree of endothelial involvement and the severity of shock. DESIGN: Observational study. SETTING: A PICU in a tertiary hospital. PATIENTS: Patients aged under 18 (n = 28) with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children and shock, according to the Centers for Disease Control and Prevention criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between endothelial marker levels and shock severity were assessed using Spearman coefficient. The median (interquartile range) age was 9 years (7.5-11.2 yr). Sixteen children presented with cardiogenic and distributive shock, 10 presented with cardiogenic shock only, and two presented with distributive shock only. The median left ventricular ejection fraction, troponin level, and lactate level were, respectively, 40% (35-45%), 261 ng/mL (131-390 ng/mL), and 3.2 mmol/L (2-4.2 mmol/L). Twenty-five children received inotropes and/or vasopressors; the median Vasoactive and Inotropic Score was 8 (5-28). Plasma levels of angiopoietin-2 (6,426 pg/mL [2,814-11,836 pg/mL]), sE-selectin (130,405 pg/mL [92,987-192,499 pg/mL]), von Willebrand factor antigen (344% [288-378%]), and the angiopoietin-2/angiopoietin-1 ratio (1.111 [0.472-1.524]) were elevated and significantly correlated with the Vasoactive and Inotropic Score (r = 0.45, p = 0.016; r = 0.53, p = 0.04; r = 0.46, p = 0.013; and r = 0.46, p = 0.012, respectively). CONCLUSIONS: Endothelial dysfunction is associated with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children with shock and may constitute one of the underlying mechanisms.


Subject(s)
COVID-19/complications , Shock/pathology , Systemic Inflammatory Response Syndrome/pathology , Adrenal Cortex Hormones/therapeutic use , Angiopoietin-2/blood , Biomarkers , C-Reactive Protein/analysis , COVID-19/drug therapy , COVID-19/pathology , Cardiotonic Agents/therapeutic use , Child , Female , Humans , Immunoglobulins/therapeutic use , Intensive Care Units, Pediatric , Interleukin-6/blood , Lactic Acid/blood , Male , Respiration, Artificial , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Shock, Cardiogenic/pathology , Systemic Inflammatory Response Syndrome/drug therapy , Troponin/blood , Vasoconstrictor Agents/therapeutic use , Ventricular Function, Left
10.
Front Cardiovasc Med ; 8: 700292, 2021.
Article in English | MEDLINE | ID: covidwho-1435983

ABSTRACT

Objective: Coronavirus disease 19 is a well-established cause of rare arterial thrombosis. Nevertheless, the exact mechanism of arterial thrombosis remains to be elucidated. We herein report the case of a large floating thrombus of the aortic arch, its surgical management and histological analysis. Case: A 65-year-old patient presented to the emergency department with a suspected stroke. He was non-smoker, but presented cardiovascular risk factors, namely hypertension, type 2 diabetes and hyperlipidaemia. A computed tomography of the aorta revealed a large floating thrombus of the aortic arch, at the base of the brachiocephalic trunk, suspected to be the etiology of stroke. Therapeutic anticoagulation was immediately started. The decision was made to perform an open aortic replacement surgery because of the symptomatic thromboembolic event with recent cerebral infarction and the potential harmfulness of the thrombus due to its size. A mobile thrombus was observed at the base of the brachiocephalic trunk by echocardiography. It was attached to a small area of the upper aortic wall and had an irregular surface. Histology revealed a platelet-rich thrombus lying on an aortic atherosclerotic plaque without pronounced inflammation. No plaque ulceration was present but endothelial cell desquamation was observed consistent with plaque erosion. Conclusion: In our case, there was a thrombus lying on an atherosclerotic plaque with intact thick fibrous cap, but associated with a plaque erosion mechanism. The thrombus formation appeared more likely to relate to a very localized endothelial injury.

11.
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
12.
Res Pract Thromb Haemost ; 5(6): e12572, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1384307

ABSTRACT

We report a case of a 62-year-old man who developed cerebral venous sinus thrombosis with subarachnoid hemorrhage and concomitant thrombocytopenia, which occurred 13 days after ChAdOx1 nCov-19 injection. The patient died in the intensive care unit after heparin infusion and platelet transfusion. The key clinical purpose of this case report is to better understand how to confirm vaccine-induced immune thrombotic thrombocytopenia (VITT). VITT diagnosis was made using 14C-serotonin release and flow cytometry evaluating activation and platelet microvesicles on washed platelets. Four control patients were examined: a patient with heparin-induced thrombocytopenia (HIT), two patients with thrombotic events without thrombocytopenia after ChAdOx1 nCov-19 or BNT162b2, and a patient with suspected HIT and an excluded diagnosis. We evidenced in the VITT case a high level of IgG anti-platelet factor 4-heparin antibodies associated with a high level of platelet activation in the absence of heparin. Conversely, the functional assays were negative in the patients with thrombosis without thrombocytopenia.

13.
Front Immunol ; 12: 701273, 2021.
Article in English | MEDLINE | ID: covidwho-1332121

ABSTRACT

SARS-CoV-2 infection leads to a highly variable clinical evolution, ranging from asymptomatic to severe disease with acute respiratory distress syndrome, requiring intensive care units (ICU) admission. The optimal management of hospitalized patients has become a worldwide concern and identification of immune biomarkers predictive of the clinical outcome for hospitalized patients remains a major challenge. Immunophenotyping and transcriptomic analysis of hospitalized COVID-19 patients at admission allow identifying the two categories of patients. Inflammation, high neutrophil activation, dysfunctional monocytic response and a strongly impaired adaptive immune response was observed in patients who will experience the more severe form of the disease. This observation was validated in an independent cohort of patients. Using in silico analysis on drug signature database, we identify differential therapeutics that specifically correspond to each group of patients. From this signature, we propose a score-the SARS-Score-composed of easily quantifiable biomarkers, to classify hospitalized patients upon arrival to adapt treatment according to their immune profile.


Subject(s)
COVID-19/immunology , SARS-CoV-2/physiology , Adaptive Immunity/genetics , Adult , Aged , Antiviral Agents/therapeutic use , Biomarkers , COVID-19/therapy , Cohort Studies , Female , Hospitalization , Humans , Inflammation/genetics , Male , Middle Aged , Precision Medicine , Prospective Studies , Severity of Illness Index , Transcriptome
14.
Ann Intensive Care ; 11(1): 113, 2021 Jul 17.
Article in English | MEDLINE | ID: covidwho-1315865

ABSTRACT

BACKGROUND: Microvascular, arterial and venous thrombotic events have been largely described during severe coronavirus disease 19 (COVID-19). However, mechanisms underlying hemostasis dysregulation remain unclear. METHODS: We explored two independent cross-sectional cohorts to identify soluble markers and gene-expression signatures that discriminated COVID-19 severity and outcomes. RESULTS: We found that elevated soluble (s)P-selectin at admission was associated with disease severity. Elevated sP-selectin was predictive of intubation and death (ROC AUC = 0.67, p = 0.028 and AUC = 0.74, p = 0.0047, respectively). An optimal cutoff value was predictive of intubation with 66% negative predictive value (NPV) and 61% positive predictive value (PPV), and of death with 90% NPV and 55% PPV. An unbiased gene set enrichment analysis revealed that critically ill patients had increased expression of genes related to platelet activation. Hierarchical clustering identified ITG2AB, GP1BB, PPBP and SELPLG to be upregulated in a grade-dependent manner. ROC curve analysis for the prediction of intubation was significant for SELPLG and PPBP (AUC = 0.8, p = 0.046 for both). An optimal cutoff value for PBPP was predictive of intubation with 100% NPV and 45% PPV, and for SELPLG with 100% NPV and 50% PPV. CONCLUSION: We provide evidence that platelets contribute to COVID-19 severity. Plasma sP-selectin level was associated with severity and in-hospital mortality. Transcriptional analysis identified PPBP/CXCL7 and SELPLG as biomarkers for intubation. These findings provide additional evidence for platelet activation in driving critical COVID-19. Specific studies evaluating the performance of these biomarkers are required.

15.
Angiogenesis ; 24(4): 755-788, 2021 11.
Article in English | MEDLINE | ID: covidwho-1286153

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is presenting as a systemic disease associated with vascular inflammation and endothelial injury. Severe forms of SARS-CoV-2 infection induce acute respiratory distress syndrome (ARDS) and there is still an ongoing debate on whether COVID-19 ARDS and its perfusion defect differs from ARDS induced by other causes. Beside pro-inflammatory cytokines (such as interleukin-1 ß [IL-1ß] or IL-6), several main pathological phenomena have been seen because of endothelial cell (EC) dysfunction: hypercoagulation reflected by fibrin degradation products called D-dimers, micro- and macrothrombosis and pathological angiogenesis. Direct endothelial infection by SARS-CoV-2 is not likely to occur and ACE-2 expression by EC is a matter of debate. Indeed, endothelial damage reported in severely ill patients with COVID-19 could be more likely secondary to infection of neighboring cells and/or a consequence of inflammation. Endotheliopathy could give rise to hypercoagulation by alteration in the levels of different factors such as von Willebrand factor. Other than thrombotic events, pathological angiogenesis is among the recent findings. Overexpression of different proangiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2) or placental growth factors (PlGF) have been found in plasma or lung biopsies of COVID-19 patients. Finally, SARS-CoV-2 infection induces an emergency myelopoiesis associated to deregulated immunity and mobilization of endothelial progenitor cells, leading to features of acquired hematological malignancies or cardiovascular disease, which are discussed in this review. Altogether, this review will try to elucidate the pathophysiology of thrombotic complications, pathological angiogenesis and EC dysfunction, allowing better insight in new targets and antithrombotic protocols to better address vascular system dysfunction. Since treating SARS-CoV-2 infection and its potential long-term effects involves targeting the vascular compartment and/or mobilization of immature immune cells, we propose to define COVID-19 and its complications as a systemic vascular acquired hemopathy.


Subject(s)
COVID-19/metabolism , Myelopoiesis , Neovascularization, Pathologic/metabolism , Respiratory Distress Syndrome/metabolism , SARS-CoV-2/metabolism , Thrombosis/metabolism , COVID-19/pathology , COVID-19/therapy , Endothelial Cells/metabolism , Endothelial Cells/pathology , Endothelial Cells/virology , Fibrin Fibrinogen Degradation Products/metabolism , Fibroblast Growth Factor 2/metabolism , Humans , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Membrane Proteins/metabolism , Neovascularization, Pathologic/pathology , Neovascularization, Pathologic/therapy , Neovascularization, Pathologic/virology , Respiratory Distress Syndrome/pathology , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , Thrombosis/pathology , Thrombosis/therapy , Thrombosis/virology , Vascular Endothelial Growth Factor A/metabolism , von Willebrand Factor/metabolism
16.
PLoS One ; 16(5): e0252026, 2021.
Article in English | MEDLINE | ID: covidwho-1243847

ABSTRACT

To investigate the mechanisms underlying the SARS-CoV-2 infection severity observed in patients with obesity, we performed a prospective study of 51 patients evaluating the impact of multiple immune parameters during 2 weeks after admission, on vital organs' functions according to body mass index (BMI) categories. High-dimensional flow cytometric characterization of immune cell subsets was performed at admission, 30 systemic cytokines/chemokines levels were sequentially measured, thirteen endothelial markers were determined at admission and at the zenith of the cytokines. Computed tomography scans on admission were quantified for lung damage and hepatic steatosis (n = 23). Abnormal BMI (> 25) observed in 72.6% of patients, was associated with a higher rate of intensive care unit hospitalization (p = 0.044). SARS-CoV-2 RNAaemia, peripheral immune cell subsets and cytokines/chemokines were similar among BMI groups. A significant association between inflammatory cytokines and liver, renal, and endothelial dysfunctions was observed only in patients with obesity (BMI > 30). In contrast, early signs of lung damage (ground-glass opacity) correlated with Th1/M1/inflammatory cytokines only in normal weight patients. Later lesions of pulmonary consolidation correlated with BMI but were independent of cytokine levels. Our study reveals distinct physiopathological mechanisms associated with SARS-CoV-2 infection in patients with obesity that may have important clinical implications.


Subject(s)
COVID-19/pathology , Cytokines/metabolism , Liver/physiopathology , Lung/physiopathology , Obesity/pathology , Aged , Biomarkers/metabolism , Body Mass Index , COVID-19/complications , COVID-19/virology , Chemokines/blood , Chemokines/metabolism , Cytokines/blood , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Female , Hospitalization/statistics & numerical data , Humans , Intensive Care Units , Liver/diagnostic imaging , Lung/diagnostic imaging , Male , Middle Aged , Obesity/complications , Prospective Studies , RNA, Viral/blood , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Severity of Illness Index
17.
Angiogenesis ; 24(3): 407-411, 2021 08.
Article in English | MEDLINE | ID: covidwho-1222775

ABSTRACT

BACKGROUND: Microthrombosis is a hallmark of COVID-19. We previously described von willebrand factor (VWF) and their high molecular weight multimers (HMWMs) as potential trigger of microthrombosis. OBJECTIVES: Investigate VWF activity with collagen-binding assay and ADAMTS13 in COVID-19. METHODS AND RESULTS: Our study enrolled 77 hospitalized COVID-19 patients including 37 suffering from a non-critical form and 40 with critical form. Plasma levels of VWF collagen-binding ability (VWF:CB) and ADAMTS13 activity (ADAMTS13:Act) were measured in the first 48 hours following admission. VWF:CB was increased in critical (631% IQR [460-704]) patients compared to non-critical patients (259% [235-330], p < 0.005). VWF:CB was significantly associated (r = 0.564, p < 0.001) with HMWMs. Moreover, median ADAMTS13:Act was lower in critical (64.8 IU/dL IQR 50.0-77.7) than non-critical patients (85.0 IU/dL IQR 75.8-94.7, p < 0.001), even if no patients displayed majors deficits. VWF:Ag-to-ADAMTS13:Act ratio was highly associated with VWF:CB (r = 0.916, p < 0.001). Moreover, VWF:CB level was highly predictive of COVID-19 in-hospital mortality as shown by the ROC curve analysis (AUC = 0.92, p < 0.0001) in which we identified a VWF:CB cut-off of 446% as providing the best predictor sensitivity-specificity balance. We confirmed this cut-off thanks to a Kaplan-Meier estimator analysis (log-rank p < 0.001) and a Cox-proportional Hazard model (HR = 49.1, 95% CI 1.81-1328.2, p = 0.021) adjusted on, BMI, C-reactive protein, and D-dimer levels. CONCLUSION: VWF:CB levels could summarize both VWF increased levels and hyper-reactivity subsequent to ADAMTS13 overflow and, therefore, be a valuable and easy to perform clinical biomarker of microthrombosis and COVID-19 severity.


Subject(s)
ADAMTS13 Protein/blood , COVID-19/blood , COVID-19/mortality , Pandemics , SARS-CoV-2 , von Willebrand Factor/metabolism , Aged , Biomarkers/blood , Collagen/metabolism , Cross-Sectional Studies , Female , Hospital Mortality , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Paris/epidemiology , Proportional Hazards Models , Protein Binding , Severity of Illness Index
19.
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
20.
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
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