Assessment of the Risk of Pulmonary Embolism and Coagulation Profile in Patients With COVID-19 Lung Disease

Study Overview
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Brief Summary
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The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is complicated by pneumonia (15 to 20% of cases) requiring hospitalization with oxygen therapy. Almost 20 to 25% of hospitalized patients require intensive care and resuscitation; half die. The main cause of death is acute respiratory distress syndrome (ARDS). However, some deaths have been linked to pulmonary embolism (PE). Recognition of PE is important because there is specific treatment to limit its own mortality. The identification of biological parameters of hemostasis predictive of thromboembolic disease is crucial in these patients. To evaluate the frequency of PE in the patients having to be hospitalized is to practice of a systematic thoracic angiography scanner in the patients having no contra-indication for its realization, as well as during hospitalization in patients deteriorating without any other obvious cause. The thromboembolic events and disturbances of the coagulation system described in patients with SARS-CoV-2 pneumonitis suggest that this viral infection is associated with an increase in the activation of coagulation contributing to the occurrence of thrombosis and especially from PE.

Detailed Description
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The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is complicated by pneumonia (15 to 20% of cases) requiring hospitalization with oxygen therapy. Almost 20 to 25% of hospitalized patients require intensive care and resuscitation; half die. On April 3, 2020, in France, 59,105 confirmed cases have been identified. 6,305 people are hospitalized in intensive care and 4,503 patients died. The main cause of death is acute respiratory distress syndrome (ARDS). However, some deaths have been linked to pulmonary embolism (PE). Very little data is available in the medical literature regarding PE during this infection. Recognition of PE is important because there is specific treatment to limit its own mortality. The identification of biological parameters of hemostasis predictive of thromboembolic disease is crucial in these patients who are difficult to mobilize. The diagnostic difficulties with traditional means, the seriousness and the ignorance of a PE make it necessary to evaluate the frequency of it in the patients having to be hospitalized by the practice of a systematic thoracic angiography scanner in the patients having no contra-indication for its realization, as well as during hospitalization in patients deteriorating without any other obvious cause. The thromboembolic events and disturbances of the coagulation system described in patients with SARS-CoV-2 pneumonitis suggest that this viral infection is associated with an increase in the activation of coagulation contributing to the occurrence of thrombosis and especially from PE. The main objective of this work is therefore to determine the incidence of the occurrence of PE in patients with hospitalized SARS-CoV-2 pneumonitis by performing systematic thoracic angiography scanner in all hospitalized patients. The secondary objective is to study the coagulation and fibrinolysis profile in these patients and to assess endothelial activation in order to better understand the physio-pathological mechanism behind PE and to determine if one of the parameters studied could be an indicator of PE risk.

Official Title
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Assessment of the Risk of Pulmonary Embolism and Coagulation Profile in Patients With SARS Coronavirus (COV-2) Lung Disease

Conditions
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Pneumonia, Viral

Intervention / Treatment
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* Radiation: Angiography scanner


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years Any patient who consults in the emergency room, COVID+ with hospitalization criteria (dyspnea or desaturation ≤ 95% or chest pain or hemoptysis), including those who have already performed a CT angiogram upon arrival at the hospital. Positive polymerase chain reaction (PCR) of coronavirus disease or compatible clinical signs associated with suggestive radiological criteria Fever Cough Myalgia Asthenia Loss of taste/ Anosmia signed informed consent before any study procedure patients affiliated to an appropriate health insurance system Exclusion Criteria: Pregnancy in progress Patient not having a microbiological diagnosis of SARS Coronavirus (COV-2) infection or whose symptoms are not suggestive < 18 years Be deprived of liberty or under guardianship Patient with contra-indication to thoracic angiography scanner: State of shock Creatinine clearance < 30 mL/mn in Chronic Kidney Disease (CKD) history of anaphylactic shock or angioedema with iodinated contrast media uncontrolled cardiac decompensation Patient with contra-indication to contrast media (Iomeron350®, Visipaque®): History of immediate major or delayed skin reaction to the injection of a contrast medium Hypersensitivity to the active substance or to any of the excipients overt thyrotoxicosis Patients with renal insufficiency and / or patients with allergy to iodinated contrast products may be included if they can perform a scintigraphy (the pulmonary scintigraphy being the alternative diagnostic to the CT angiography for renal insufficiency and / or allergy to iodinated contrast products).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Determination of incidence of occurrence of pulmonary embolism in hospitalized patients with SARS-CoV-2 pneumonitis, first by performing systematic thoracic angiography scanner in all hospitalized patients and then to explore hemostasis profile
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hospitalized SARS Cov-2<br>Hospitalized patients diagnosed with SARS Cov-2 infection | Radiation: Angiography scanner<br>* systematic thoracic angiography scanner to diagnose pulmonary embolism and additional blood sample (hemostasis exploration)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients with pulmonary embolism | Rate of patients with pulmonary embolism diagnosed by thoracic angiography scanner | up to Day 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prothrombin level measurement | Measure of prothrombin level to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization | up to Day 12 | 
| activated partial thromboplastin time measurement | Measure of activated partial thromboplastin time to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization | up to Day 12 | 
| Fibrinogen measurement | Measure of fibrinogen to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization | up to Day 12 | 
| D-dimers measurement | Measure of D-dimers to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization | up to Day 12 | 
| Protein C measurement | Measure of Protein C to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization | up to Day 12 | 
| Willebrand antigen measurement | Measure of Willebrand antigen to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization | up to Day 12 | 
| Soluble tissue factor measurement | Measure of Soluble tissue factor to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization | up to Day 12 | 
| Soluble thrombomodulin measurement | Measure of soluble thrombomodulin to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization | up to Day 12 | 
| E-selectin measurement | Measure of E-selectin to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization | up to Day 12 | 
| Thrombin-antithrombin complex measurement | Measure of thrombin-antithrombin complex to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization | up to Day 12 | 
| Assessment of clot formation curve | Assessment of clot formation curve by Thrombodynamics® to identify ones predictive of the onset of Pulmonary Embolism or a poor prognosis | Day 1 | 
| Assessment of thrombin generation | Assessment of thrombin generation by Thrombodynamics® to identify ones predictive of the onset of Pulmonary Embolism or a poor prognosis | Day 1 | 
| Assessment of fibrinolysis | Assessment of fibrinolysis by Thrombodynamics® to identify ones predictive of the onset of Pulmonary Embolism or a poor prognosis | Day 1 | 
| Mortality | Determine patient mortality | Day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS COV-2, pulmonary embolism, acute respiratory distress syndrome, coagulation disorders, venous thromboembolic disease