Novel coronavirus COVID-19 has become a health emergency around the world. Since first patients were detected in Wuhan China, in December 2019, COVID-19 has spread quickly worldwide, being a severe threat to public health. Fever, dry cough, shortness of breath and breathing distress are the main characteristics of COVID-19 infection. Some patients develop overwhelming lung inflammation and acute respiratory failure, for which there is no specific therapy. Therefore, safe and effective treatment for COVID-19 pneumonia is utterly necessary, mainly in critical cases. Mesenchymal stem 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. These immunomodulatory properties of MSCs support performance of the phase I/II, placebo- controlled, randomized MSCs for treatment of severe COVID-19 pneumonia.
Novel coronavirus COVID-19 has spread quickly from Wuhan China to worldwide. On 15 April
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 COVID-19 specifically recognized the angiotensin I converting ezyme
2 repector (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. COVID-19 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 COVID-19 enters in blood circulation, it can easy 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 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 virus,
reducing proinflammatory cytokines and inflammatory cells into the lungs.
These immunomodulatory properties of MSCs support performance of the Phase I/II, double-blind
(neither the participant nor the investigator will know if active drug or placebo is
assigned), placebo-controlled, randomized (assigned by chance), in which subjects with severe
COVID-19 pneumonia shall be received either MSCs (1 million cells/kg) or placebo by
intravenous injection. The administration of cells will be done only once.
Biological: Mesenchymal Stromal Cells
Intravenous injection of 1 million MSV cells/Kg diluted in 100 ml saline
Other Name: MSV
Other: Placebo
Intravenous injection of 100 ml saline containing no cells
Inclusion Criteria:
1. Women or men of ≥ 18 years of age
2. SARS-CoV-2 infection confirmed by molecular testing.
3. Admitted to the Intensive Care Unit with pneumonia by COVID-19 infection in the last
48 hours, that meet at least one of these criteria:
1. Respiratory distress.
2. Respiratory rate (FR) ≥ 30 rpm.
3. Basal oxygen saturation at rest ≤ 93%.
4. Arterial partial pressure of oxygen (PaO₂) / inspiratory fraction of oxygen
(FiO₂) ≤300mmHg
4. Consent of the patient or his legal representative for participation in the study.
Exclusion Criteria:
1. Active tumor disease.
2. Pregnancy.
3. Participation in another clinical trial for the same pathology.
4. Any circumstance that in the researcher's opinion justifies the patient's
non-participation in the trial.
5. Lack of signed consent for participation.
Hospital Universitario Rio Hortega
Valladolid, Spain