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.