SARCODO: Coagulopathy and Vasculopathy Assessment as a Predictor of the Severity of SARS-CoV-2 / COVID-19 Infection
Study Details
Study Description
Brief Summary
On 30 January 2020, WHO declared the SARS-CoV-2 outbreak as a public health emergency of international concern. Compared to SARS-CoV, which caused an outbreak of SARS in 2003, SARS-CoV-2 has a higher transmission capacity. Although the clinical manifestations of SARS-CoV-2 are dominated by respiratory symptoms, some patients have severe cardiovascular damage. In addition, patients with underlying cardiovascular disease may be at increased risk of death. Therefore, understanding the impairments caused by SARS-CoV-2 to the cardiovascular system and the underlying mechanisms is of the utmost importance.
Circulating endothelial cells (CECs) are generally considered markers of lesions and may be non-invasive markers of pulmonary vascular dysfunction during SARS-CoV-2 infection. Another marker of endothelial activation could be circulating extracellular vesicles. They could also be involved in the spread of the virus. Thus this project proposes to study different aspects of the diagnosis and pathophysiology of SARS-CoV-2. We propose to fully study activation state of coagulation and endothelium on a plasma and cellular side in patients diagnosed with SARS-CoV-2/COVID19. The different forms of the disease will be included: without lung disease, with a more or less severe lung disease, i.e. having evolved or not towards acute respiratory distress syndrome (ARDS). Extensive research of biomarkers will be compared to the detection of the virus in the respiratory tract as well as in the blood. This work will contribute to a better description of disease pathophysiology and should allow us to identify a patient profile in whom preventive or curative anticoagulant therapy could be considered.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
In December 2019, an outbreak of pneumonia caused by a new coronavirus occurred in Wuhan and spread rapidly throughout China, with the evolution towards a global pandemic. Originally called new coronavirus 2019 (2019-nCoV), the virus was later officially named Coronavirus 2 of Severe Acute Respiratory Syndrome (SARS-CoV-2) by WHO. On 30 January 2020, WHO declared the SARS-CoV-2 outbreak as a public health emergency of international concern. Compared to SARS-CoV, which caused an outbreak of SARS in 2003, SARS-CoV-2 has a higher transmission capacity. Although the clinical manifestations of SARS-CoV-2 are dominated by respiratory symptoms, some patients have severe cardiovascular damage. In addition, patients with underlying cardiovascular disease may be at increased risk of death. Therefore, understanding the impairments caused by SARS-CoV-2 to the cardiovascular system and the underlying mechanisms is of the utmost importance. During this Chinese epidemic, a coagulopathy was found in severe cases of SARS-CoV-2 infection, including significantly higher levels of D-dimers in severe forms, disturbed PT and aPTT ratio compared to survivors (P <0.05). 71.4% of non-survivors and 0.6% of survivors met the criteria for disseminated intravascular clotting during their hospital stay. This study was confirmed in a second Chinese population where DDimers are still correlated with mortality. The hypothesis of microthrombosis at the renal level was also associated with activation of coagulation since high levels of creatinine were associated with higher levels of DDimers, in favor of a thrombotic origin for kidney failure. Endothelial dysfunction may thus have a major role in the respiratory physiopathologic process as well as in the viral dissemination processes. Indeed, the SARS-CoV-2 receptor (ACE2) is strongly expressed in endothelial cells. Infection of endothelial cells could cause a lesion of the endothelium but also an activation that can trigger the activation of coagulation. Circulating endothelial cells (CECs) are generally considered markers of lesions and may be non-invasive markers of pulmonary vascular dysfunction during SARS-CoV-2 infection. Another marker of endothelial activation could be circulating extracellular vesicles. They could also be involved in the spread of the virus. Thus this project proposes to study different aspects of the diagnosis and pathophysiology of SARS-CoV-2. We propose to fully study activation state of coagulation and endothelium on a plasma and cellular side in patients diagnosed with SARS-CoV-2/COVID19. The different forms of the disease will be included: without lung disease, with a more or less severe lung disease, i.e. having evolved or not towards acute respiratory distress syndrome (ARDS). Extensive research of biomarkers will be compared to the detection of the virus in the respiratory tract as well as in the blood. This work will contribute to a better description of disease pathophysiology and should allow us to identify a patient profile in whom preventive or curative anticoagulant therapy could be considered.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Patient suspected COVID-19 Follow-up of patients as usual in care for infection. No specific puncture. Blood sample collect at admission and every 72h during hospitalisation for hemostasis evaluation, DNA extraction, Circulating endothelial cells measuring. Sampling can be delayed for 24h to match a planned blood collection for care or other research. |
Other: biological sample
biological sample
|
Outcome Measures
Primary Outcome Measures
- Measure D-dimers (ng/ml) to study coagulopathy to characterize COVID-19 [28 days]
Characterize COVID-19 and identify patient populations who will develop or aggravate a micro or macro thrombotic process
- Measure fibrin monomers (µg/ml) to study coagulopathy to characterize COVID-19 [28 days]
Characterize COVID-19 and identify patient populations who will develop or aggravate a micro or macro thrombotic process
Secondary Outcome Measures
- Study troponin (ng/ml) to characterize COVID-19 and identify patient populations who will develop or aggravate a micro or macro thrombotic process [28 days]
- Study von Willebrand factor antigen (%) to characterize COVID-19 and identify patient populations who will develop or aggravate a micro or macro thrombotic process [28 days]
- Study association of genetical and constitutive factors of thrombophilia :blood type ABO and COVID-19 severity according to OMS classification [28 days]
- Study association of genetical and constitutive factors of thrombophilia: deficit in S protein and COVID-19 severity according to OMS classification [28 days]
- Study association of genetical and constitutive factors of thrombophilia:deficit in C protein and COVID-19 severity according to OMS classification [28 days]
- Study association of genetical and constitutive factors of thrombophilia: mutation in V factor of coagulation and COVID-19 severity according to OMS classification [28 days]
- Study association of genetical and constitutive factors of thrombophilia:mutation in II factor of coagulation and COVID-19 severity according to OMS classification [28 days]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients at least 18 years old
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Hospitalized for suspected COVID-19 in the medical wards or intensive care unit.
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Patients benefiting from a social security scheme
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Patient who has been informed of the study
Exclusion Criteria:
- Patients under guardianship / curatorship
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hôpital Cochin | Paris | France | 75014 | |
| 2 | Hôpital Européen Georges Pompidou | Paris | France | 75015 |
Sponsors and Collaborators
- Assistance Publique - Hôpitaux de Paris
- National Research Agency, France
Investigators
- Principal Investigator: David M Smadja, HEGP, AP-HP
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- APHP200521
- 2020-A01048-31