Efficacy of Infusions of MSC From Wharton Jelly in the SARS-Cov-2 (COVID-19) Related Acute Respiratory Distress Syndrome

Mesenchymal stem cells (MSCs) are of potential help in acute respiratory distress syndrome (ARDS), due to their anti-inflammatory properties.

The investigators will analyze the effect of 3 iterative infusions of ex vivo expanded Wharton's Jelly MSCs (total dose 2.10\^6/kg) in patients with ARDS due to COVID19, who require mechanical ventilation.

This study is designed to analyze the impact of Wharton's Jelly Mesenchymal Stem Cells on moderate to severe ARDS due to COVID19 in adult patients who require mechanical ventilation. It is a Phase IIa double-blind randomized controlled trial.

30 patients are planned.

Patients will be randomized and will receive, with the conventional treatment recommended to treat ARDS:

* Either Wharton's Jelly MSCs in a solution of albumin 4% (40% of final volume), NaCl 0,9% (50% of the final volume) et ACD formule A (10% of the final volume) . Treatment will be administered intravenously during 10 minutes following that scheme:

  * Day 0 (or 1): 1. 10\^6 MSC/kg (maximum 80.10\^6 MSC)
  * Day 3 (or 4): 0.5 . 10\^6 MSC/kg (maximum 40. 10\^6 MSC)
  * Day 5 (or 6): 0.5 . 10\^6 MSC/kg (maximum 40. 10\^6 MSC) An interval of 2 days will be respected between 2 infusions.
* Either a placebo, which contains the same solution of albumin, NaCl 0.9% and ACD without cells. The volume will be of 75 ml, infused in 10 minutes.

The main objective is to investigate efficacy of WJ-MSCs, compared to a placebo, on respiratory function evolution during the first 14 days of study treatment in patients with SARS-CoV-2 related moderate to severe ARDS.

Secondary objectives are to assess the effect of WJ-MSC, compared to placebo, in patients with SARS-CoV-2 related moderate to severe ARDS, on:

1. the duration of invasive mechanical ventilation during the hospital stay and maximum for 28 days
2. the evolution of organ failures during the hospital stay and maximum for 28 days
3. the duration of stay in intensive care unit, the mortality during intensive care unit, during hospitalization, on D28 and D90, and the respiratory morbidity.
4. the evolution of viral load between D0 and D28
5. the immediate or delayed tolerance following the WJ-MSCs injection

Eligibility Criteria:
Inclusion Criteria:

1. Man or woman 18 years of age or older
2. Patient with a biologically confirmed SARS-CoV-2 infection (by positive RT-PCR on a nasopharyngeal sample or any other sample)
3. Patient with moderate to severe ARDS according to the BERLIN definition defined by a PaO2 / FiO2 ratio \<200 and with endotracheal intubation and under invasive mechanical ventilation
4. Patient hospitalized in the intensive care unit
5. Provision of a written informed consent to participate to the study or for whom the consent of a family member or support person has been obtained (if the patient is unable to give consent) or inclusion in an immediate vital emergency if applicable
6. Any woman of childbearing age with a negative Beta HCG test
7. Social Security affiliation

Exclusion Criteria:

1. Patient under invasive mechanical ventilation for more than 48 hours
2. Patient with a chronic respiratory disease under oxygen therapy
3. Patients with a history of Class III or IV pulmonary arterial hypertension (WHO classification)
4. Patients under ECMO
5. Immunosuppressive therapy (including corticosteroid therapy\> 20 mg prednisolone)
6. Active solid tumor or in remission for less than 2 years, malignant hematological disease, asplenia
7. Patient who has received a hematopoietic stem transplantation or an organ transplant
8. Therapeutic limitations like progression to expected death within 24 hours (according to the opinion of the medical team)
9. Hypersensitivity to albumin or to any of the excipients (caprylic acid or sodium caprylate)
10. Patient included in another ongoing interventional therapeutic trial
11. Pregnant woman, parturient, nursing mother
12. Minor (not emancipated)
13. Person without liberty by judiciary or administrative decision
14. Person undergoing psychiatric care under Articles L. 3212-1 and L. 3213-1 which do not fall under the provisions of Article L. 1121-8 (hospitalization without consent).
15. Adult over 18 who are under a legal protection measure