Safety and Feasibility of Allogenic MSC in the Treatment of COVID-19

Study Overview
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Brief Summary
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Coronavirus Disease 2019 (COVID-19) is spreading worldwide and has become a public health emergency of major international concern. Currently, no specific drugs or vaccines are available. For severe cases, it was found that aberrant pathogenic T cells and inflammatory monocytes are rapidly activated and then producing a large number of cytokines and inducing an inflammatory storm. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate the safety and efficacy of intravenous infusion of mesenchymal stem cells in severe patients with COVID-19.

Detailed Description
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Coronavirus-19 Disease (COVID-19), caused by the Sars-Cov-2 virus, which occurs as a growing pandemic in early 2020 and currently represents an emergency state worldwide. Several reports have shown that the first step in the pathogenesis of Sars-Cov-2 is the recognition of the angiotensin I converting enzyme (ACE2) receptor by the virus. This ACE2 receptor is widely distributed on the surface of human cells, especially as type II alveolar cells and capillary endothelium, however bone marrow, lymph nodes, thymus and spleen are known as immune cells, such as T and lymphocytes. B and macrophages, are negatives to ACE2. These results suggest that immunotherapy can be used to treat infected patients. However, an immunomodulatory capacity cannot be so strong, if just one or two major immunological factors used, as the virus can cause a cytokine storm, such as IL-2, IL-6, IL-7, GSCF, IP10 , MCP1, MIP1A and TNFα, followed by edema, gas exchange dysfunction, acute respiratory distress syndrome, cardiac injury and secondary infection that can lead to death. Therefore, avoiding a cytokine storm may be the key to treating patients infected with Sars-Cov-2. Mesenchymal stem cells (MSCs), due to their potential for immunomodulatory activity, can have beneficial effects in preventing or attenuating the cytokine storm. Because MSCs have been widely used in cell therapy, from basic research to clinical trials. Safety and efficacy have been clearly documented in several clinical trials, especially in immune-mediated inflammatory diseases, such as graft versus host disease (GVHD). The objective of the study is to verify the safety and feasibility of using allogeneic bone marrow mesenchymal stem cells in patients with SARS-CoV-2.

Official Title
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Safety and Feasibility of Allogenic Mesenchymal Stromal Cells in the Treatment of COVID-19

Conditions
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COVID-19, Sars-CoV2

Intervention / Treatment
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* Biological: Mesenchymal Stromal Cells infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Laboratory confirmation of COVID19 infection by reverse-transcription polymerase chain reaction (RT-PCR) The patient or legal donor agrees to participate in the study and signs the informed consent. Patients with orange or red criteria according to the score proposed by Liao et al (2020) Exclusion Criteria: Patient with pregnancy, are planning to become pregnant or breastfeeding Patients with malignant blood-borne diseases such as HIV or syphilis Not consenting for clinical trial Patients with other than orange or red criteria according to the score proposed by Liao et al (2020)
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Intravenous 1*10E6 MSCs/kg body weight Mesenchymal Stromal Cells infusion | Biological: Mesenchymal Stromal Cells infusion<br>* Intravenous 1*10E6 MSCs/kg body weight Mesenchymal Stromal Cells infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Assessment of Overall survival at 30 days post intervention | 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes on inflammatory C-reactive protein | To assess the anti-inflammatory effect of the proposed treatment with assessment of the levels of C-reactive protein (mg/dL) | 60 days | 
| Hospital stay | days of the patients in hospital | 60 days | 
| Oxygenation index (PaO2/FiO2) | Evaluation of functional respiratory changes: PaO2 / FiO2 ratio | 60 days | 
| Improvement in Liao's score (2020) | Improvement in Liao's score (2020) | 60 days | 
| Radiological improvement | Computed tomography Chest assesment will be done to assess improvement in radiological findings of COVID-19 | 60 days | 
| Time of COVID19 PCR negativity | PCR testing to check PCR negativity | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal Stromal Cells, COVID-19, Sars-CoV2