Endothelial damage and coagulation activation at the lung microvascular level may play an important role in the physiopathology of the COVID-19 ARDS. The project aims to prospectively investigate both bedside pulmonary physiological markers (mainly alveolar dead-space) and biological markers of coagulopathy and endothelial dysfunction in COVID-19 and non-COVID-19 ARDS patients. In December 2019, an outbreak of pneumonia caused by a new coronavirus occurred in Wuhan and spread rapidly throughout China, with an 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. The clinical manifestations of severe forms of SARS-CoV-2 are dominated by respiratory symptoms, leading in the more severe cases to Acute Respiratory Distress syndrome (ARDS). Understanding the impairments caused by SARS-CoV-2 to the respiratory and vascular systems and the underlying mechanisms is of an utmost importance. A coagulopathy is found in severe cases of SARS-CoV-2 infection, including significantly higher levels of D-dimers in severe forms and fatalities as compared to survivors. Accordingly, the hypothesis of microthrombosis at the organ level was first proposed for renal injury. High levels of creatinine were associated with higher levels of D-Dimers, which could suggest a micro-thrombotic origin for kidney failure. Thereafter, pulmonary thrombotic complications were reported both at the pulmonary arterial level and at the rich capillary lung level. Endothelial dysfunction (triggered by endothelial cells viral infection) and its microthrombotic consequences may thus play a major role in the respiratory physiopathologic process. Indeed, the SARS-CoV-2 receptor (ACE2) is strongly expressed in lung cells, preferentially alveolar type II cells, but also lung 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 markers of severe endothelial lesions and may act as non-invasive markers of pulmonary vascular dysfunction during SARS-CoV-2 infection, beside other biological markers of endothelial dysfunction. CECs are defined by a number of phenotypic and functional morphological criteria, which differentiate them from endothelial progenitor cells. Physiological bedside respiratory markers, such as physiological dead-space and more importantly alveolar dead-space, extracted from the advanced pulmonary monitoring performed in ARDS patients, could be highly correlated to such markers. Accordingly, the translational project proposes to study different aspects of the underlying pathophysiology of SARS-CoV-2 ARDS and to support specific therapeutic approaches. We propose to fully study in SARS-CoV-2 ARDS patients: (i) bedside pulmonary physiological parameters during the ICU clinical course, with alveolar dead-space as a major study parameter (ii) coagulation and fibrinolytic systems and (iii) endothelium activation and senescence. This work will contribute to a better description of the SARS-CoV-2 ARDS pathophysiology and should allow identifying patients' profile in which curative anticoagulant therapy or even thrombolytic treatments could be considered. Additionally, specific mechanical ventilator settings could also be proposed.