In this randomized controlled trial (RCT), severe cases of COVID-19 infection will be treated with secretome of hypoxia-mesenchymal stem cells. The improvement in clinical, laboratory, and radiological manifestations will be evaluated in treated patients compared with the control group.
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 reported a correlation between disease severity and the release of excessive
proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), IL-6, IL-1, IFN-Υ,
IFN-Υ-induced protein 10 (IP10), monocyte chemoattractant protein-1 (MCP-1), macrophage
inflammatory protein-1a (MIP-1a), and granulocyte-colony stimulating factor (G-CSF). This
finding was confirmed by the high level of plasma cytokines found in most severe COVID-19
patients associated with extensive lung damage. Therefore, finding an effective therapeutic
option to control the devastating cytokine storm of COVID-19 and regenerate the damaged lung
is crucial.
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.
Biological: Injection of Secretome-MSCs
Injection of Hypoxic Secretome-MSCs intramuscular (deltoideus) :
Day 1: 1 cc every 12 hours
Day 2: 1 cc every 12 hours
Day 3: 1 cc every 12 hours
Drug: Standard treatment of Covid-19
Patients will be given Standard treatment of Covid-19 which accordance with National protocol
Inclusion Criteria:
1. Patients whose clinical and laboratory test results have a positive diagnosis of
Covid-19.
2. Patients who are willing to participate as subjects in the study by signing the
informed content.
3. Criteria for Berlin to enter ARDS (moderate and severe) with or without a ventilator:
- PaO2 / FiO2: moderate 100-200
- PaO2 / FiO2: severe <100
4. One or more comorbid history
5. SOFA score
Exclusion Criteria:
1. The Covid19 patient has fibrosis (based on the results of the chest X-ray or CT chest)
2. ECOG 4 performance status, decreased irreversible consciousness, brain stem death.
3. Severe NYHA III / IV heart failure
4. Pregnant women
RSUD Bantul
Bantul, Central Java, Indonesia
RS PKU Muhammadiyah Gamping
Yogyakarta, Central Java, Indonesia
RS Primaya Bekasi Timur
Bekasi, Jakarta, Indonesia
Bhayangkara Hospital
Makassar, South Celebes, Indonesia
Gatot Soebroto Army Hospital
Jakarta, Indonesia
Dr. Esnawan Antariksa Air Force Hospital
Jakarta, Indonesia
Agung Putra, Assoc.Prof
+628164251646
dr.agungptr@gmail.com
Bhirau Wilaksono, MD
+6285277777824
bhirau@gmail.com
Agung Putra, Assoc.Prof, Principal Investigator
Stem Cell and Cancer Research Indonesia