Treatment of Severe COVID-19 Pneumonia With Allogeneic Mesenchymal Stem Cells

Novel coronavirus disease COVID-19, produced by SARS-CoV-2, has spread quickly from Wuhan (China) to worldwide. On April 15, 2020, the World Health Organization (WHO) has reported 1.914.916 confirmed cases and 123.010 deaths globally, being a severe threat to public health.

Some patients develop overwhelming lung inflammation and acute respiratory failure. Several reports demonstrated that SARS-CoV-2 specifically recognize the angiotensin I converting ezyme 2 receptor (ACE2) and ACE2-positive cells are infected by the virus. ACE2 receptor is widely present on the human cells surface such as alveolar type II cells and capillary endothelium, among others. SARS-CoV-2 infects cells and stimulates a terrible cytokine storm in the lung followed by edema, dysfunction of the air exchange and acute respiratory distress which may lead to death. Further, once SARS-CoV-2 enters in blood circulation, it can easily spread to some systems and organs, causing significant damage. Under these circumstances, it is reasonable to believe that the inhibition of inflammatory response is the key to treat COVID-19 pneumonia.

Mesenchymal stem/stromal cells (MSCs) have been widely used in the immune-mediated inflammatory diseases. MSCs can regulate both innate and adaptive immunity by suppressing the proliferation, differentiation and activation of different cells. Some studies have shown that MSCs can significantly reduce acute lung injury in mice caused by H9N2 and H5N1 viruses, reducing proinflammatory cytokines and inflammatory cells into the lungs.

These immunomodulatory properties of MSCs support performance of the placebo-controlled, double-blind (neither the participant nor the investigator will know if active drug or placebo is assigned), randomized (assigned by chance), phase I/II clinical trial in which subjects with severe COVID-19 pneumonia will receive either MSCs (1 million cells/kg) or placebo by intravenous injection. The administration of cells will be done only once.

Inclusion criteria

• Women or men of ≥ 18 years of age
• SARS-CoV-2 infection confirmed by molecular testing.
• Admitted to the Intensive Care Unit with pneumonia by COVID-19 infection and intubated in the last 48 hours, that meet at least one of these criteria:

• Respiratory distress.
• Respiratory rate (RR) ≥ 30 rpm.
• Basal oxygen saturation at rest ≤ 93%.
• Arterial partial pressure of oxygen (PaO2) / inspiratory fraction of oxygen (FiO2) ≤ 300 mmHg.
• Consent of the patient or his/her legal representative for participation in the study.

Exclusion criteria

• Active tumor disease.
• Pregnancy.
• Participation in another active clinical trial.
• Any circumstance that in the researcher's opinion justifies the patient's non-participation in the trial.
• Not consent to participation.