Clinical Use of Stem Cells for the Treatment of Covid-19
Condition: Covid19; Pneumonia; Multiple Organ Failure; Corona Virus Infection
MeSH terms: COVID-19; Pneumonia; Coronavirus Infections; Multiple Organ Failure
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This study aims to use the regenerative and repair abilities of stem cells to fight against
      the harmful effects of the novel coronavirus Covid-19 and therefore develop a treatment
      strategy. It is known that fatalities from this virus is largely caused by its damage to
      lungs and other organs. As the disease progresses, these organs fail and lead to mortality.
      Our hope is that the stem cell transplantation from healthy donors will repair the damage
      caused by the virus and result in a healthy recovery.
    

Detailed description: 
      Introduction:

      The COVID-19 corona virus epidemic has spread from Wuhan, China to the whole world, and has
      been declared a pandemic by WHO worldwide. In severe patients, ARDS and multiple organ
      failure can be seen. This condition is associated with cytokine storm in the body. When the
      virus invades the body, dentric cells can activate macrophages, lymphocytes and natural
      killer cells. Mesenchymal stem cells (MKH) not only inhibit the abnormal activation of T
      lymphocytes and macrophages, but also encourage them to differentiate into regulatory T cell
      subsets (Treg) clusters and anti-inflammatory macrophages. MSCs application proved
      therapeutic efficiency during influenza infection resulting in reduced impairment of alveolar
      fluid clearance and lung injury. This was attributed towards attenuation of pro-inflammatory
      cytokine secretion, inflammatory cell recruitment and increased alveolar macrophages content.

      Aim of study:

        1. To provide immune modulation to patients with COVID-19 who are taken to intensive care
           and resistant to treatment by performing MSCs transplantation and to reduce the damage
           caused by cytokin storm to tissues and organs,

        2. Correcting immunosuppression in patients and increasing the fight against COVID-19 virus
           by CD4+T, CD+8T cellular cell arrangement,

        3. It is to accelerate the recovery in organ damage by increasing growth factors by means
           of MSCs.

      Materials and method:

      Patients diagnosed with COVID-19 infection as clinically, radiologically and laboratory-wise
      will be divided into three groups:

      Group 1: patients that are not on a ventilator (n=10) Group 2: patients that are on a
      ventilator and will receive saline injections (n=10) Group 3: patients that are on a
      ventilator and will receive MSC transplantation injections (n=10)

      Mesenchymal stem cells originating from allogenic umbilical cord produced under GMP
      conditions will be administered in 3 times, with doses indicated below, intravenously within
      1 week.

      Dose:

        1. Application: 3 million cells / kg IV ---------------------------------------- ---------
           1 day

        2. Application: 3 million cells / kg IV ---------------------------------------- ---------
           3. Day

        3. Application: 3 million cells / kg IV ---------------------------------------- ---------
           6. Day

      The blood will be analyzed for the expression levels of growth factors, including vascular
      endothelial growth factor, fibroblast growth factor, platelet derived-growth factor,
      epidermal growth factor, transforming growth factor beta, hepatocyte growth factor, nerve
      growth factor, VEGF receptor (VEGFR), angiopoietin1 (Angpt-1), and Angpt-2, using sandwich
      enzyme-linked immune sorbent assays (ELISAs). Investigators also analyzed the caspase-3
      system in the blood. immunoassay kits will be used for analyses in accordance with the
      manufacturer's instructions.

      Biochemical parameters of the liver, such as alanine transaminase (ALT), aspartate
      transaminase (AST), total protein, albumin, total bilirubin, direct bilirubin, and alkaline
      phosphatase (ALP) levels, will be measured in the venous blood samples.

      Proinflammatory (IL1-β, IL-6, TNFα, INF-γ) and anti-inflammatory (IL-2, IL-4, IL-10, IL-13)
      cytokines will be examined in venous blood in order to determine the immune modulatory effect
      of stem cells. CD4 + T, CD4 + T killer cells Granulocyte macrophage colony factor BLC-2
      VEGF-R angiopoetin-1, angiopoetin-2 Total antioxidant capacity (TAC) Total oxidant capacity
      (TOC).
    

Intervention name(s): MSC Treatment; Saline Control
Intervention type(s): Biological; Biological
Intervention description(s): Protocol length: 1 week
Doses:
Application: 3 million cells/kg IV-------------------------------------------------0 day
Application: 3 million cells/kg IV ------------------------------------------------3rd day
Application: 3 million cells/kg IV -------------------------------------------------6th day
will be given to patients positively, clinically and radiologically diagnosed with COVID-19, followed with 3 months observation.; Saline will be given to patients positively, clinically and radiologically diagnosed with COVID-19, followed with 3 months observation.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Covid-19; Pneumonia; Multiple Organ Failure; Coronavirus; Mesenchymal stem cells; Cellular therapy