Menstrual Blood Stem Cells in Severe Covid-19
Condition: Covid19; Cytokine Storm
MeSH terms: COVID-19; Cytokine Release Syndrome
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      In this randomized controlled trial (RCT), severe cases of COVID-19 infection will be treated
      with secretome of menstrual blood stem cells. The improvement in the clinical, laboratory and
      radiological manifestations will be evaluated in treated patients compared with the control
      group.
    

Detailed description: 
      The devastating effect of severe acute respiratory syndrome coronavirus-2 (SARS COV-2)
      infection is caused by a robust cytokine storm that leads to lung tissue damage. Several
      studies have found that the severity of the disease is correlated with the release of
      excessive proinflammatory cytokines, such as IL-1, IL-6, IL-12, IFN-γ, and TNF-α,
      preferentially targeting lung tissue. This finding was confirmed by the high level of plasma
      cytokines found in the most severe COVID-19 patients associated with extensive lung damage.
      As a result, it is essential to find an effective treatment option to control the devastating
      cytokine storm of COVID-19 and regenerate the damaged lung. Although mesenchymal stem cells
      are a powerful tool for clinical applications, they have limits in terms of administration,
      safety, and variability of therapeutic response. It is interesting to note that the MSC
      secretome composed of cytokines, chemokines, growth factors, proteins, and extracellular
      vesicles could be a valid alternative to their use. It is not only easier to preserve,
      transfer and produce the secretome, but also safer to administer.

      Previous studies reported that the hypoxic condition of MSCs could enhance the release of
      their active soluble molecules known as Secretome-MSCs (S-MSCs), such as IL-10 and TGF-β that
      useful in alleviating inflammation. Moreover, they could also increase the expression of
      growth factors such as VEGF and PDGF that accelerate lung injury improvement. These active
      molecules could potentially serve as a biological therapeutic agent for treating the severe
      SARS-CoV-2 infection. According to recent studies, we successfully isolated the S-MSCs from
      their culture medium using tangential flow filtration (TFF) strategy with several molecular
      weight cut-off category. This study investigated the clinical outcomes of severe COVID-19
      patients with several comorbidities treated with S-MSCs in Indonesia.
    

Intervention name(s): Allogeneic human menstrual blood stem cells secretome; Intravenous saline injection
Intervention type(s): Biological; Other
Intervention description(s): This COVID-19 Study intervention consists of Intravenous Allogeneic human menstrual blood stem cell (MenSC) secretome injection in addition to standard care. The MenSC were characterized as CD90+, CD73+, CD105+, and CD45-based on multiparameter flow cytometry.; Intravenous saline injection in addition to standard care
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Biological: allogeneic human menstrual blood stem cells secretome Intravenous injection of 5 ml menstrual blood stem cells secretome on day 1, day 2, day 3, day 4, and day 5, based on the routine treatment of COVID-19
Other: Intravenous saline injection (Placebo) Intravenous injection of 5ml of 0.9% saline on day 1, day 2, day 3, day 4, and day 5, based on the routine treatment of COVID-19
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: mesenchymal stem cells; menstrual blood stem cell; secretome; covid-19