Coagulopathy and Vasculopathy Assessment as a Predictor of the Severity of SARS-CoV-2 / COVID-19 Infection

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.