Efficacy of Intravenous Infusions of Stem Cells in the Treatment of COVID-19 Patients
Condition: Corona Virus Infection
MeSH terms: COVID-19; Coronavirus Infections
Study type: Interventional
Phase: Phase 2

Summary: 
      Stem cell therapy has emerged as a revolutionary treatment for diseases that were considered
      untreatable only a few years ago. Umbilical cord-derived mesenchymal stem cells (UCMSCs) have
      been shown to repair damaged liver, kidney, heart, pancreas, skin, cartilage, and cornea in
      animal models and several human trials. In addition to cellular replacement through
      regeneration, UCMSCs mediate through paracrine signaling pathways resulting in immune
      modulation. Clinical manifestations of coronavirus disease 2019 (COVID-19), are believed to
      arise from septic shock and cytokine storm that cause acute respiratory dysfunction and acute
      cardiac injury. There is presently no cure for the COVID-19 viral disease; however,
      multi-treatment strategies are being examined. During the past two months, four reports were
      published that suggest, mesenchymal stem cells (MSCs), owing to their powerful
      immunomodulatory ability, may prevent the cytokine storm and thus reduce the COVID-19 related
      morbidity. All studies reported that COVID-19 patients responded favorably to MSCs therapy.
      These reports, taken together with the previous successes of stem cell therapy in animal
      models, the investigators, a seven-institution consortium, propose to explore the efficacy of
      UCMSC treatment in COVID-19 patients at Jinnah hospital, Lahore. The investigators propose to
      administer UCMSCs in patients with acute pulmonary inflammation due to COVID-19 infection
      with moderate to severe symptoms. In the first cohort of 15 patients, UCMSCs will be
      administered with three intravenous infusions of 500,000 UCMSCs per Kg body weight each on
      days 1, 3, and 5. The second group of five patients serving as control will only receive
      standard treatment. During the 30-day post-infusion period, a battery of tests will be
      performed to evaluate the safety and efficacy of the UCMSCs treatment. In parallel, the
      investigators propose a comparative study to determine COVID-19 viral count by quantitative
      real-time PCR and through viral coat protein ELISA, developed in the investigator advisor lab
      (Dr. Tauseef Butt, Progenra Inc. Philadelphia, USA) with the ultimate objective to locally
      developing a rapid diagnostic assay.
    

Detailed description: 
      Isolation and characterization of human umbilical cord-derived mesenchymal stem cells
      (UCMSCs): Human umbilical cord tissues along with informed consent forms will be collected
      from hepatitis B, C, and COVID-19 virus-negative women with healthy pregnancies during the
      Cesarean Section surgery after completion of gestation period. The cord tissue will be
      transported in sterile 1x phosphate-buffered saline (PBS) containing 200 units/ml penicillin
      and 200 µg/ml streptomycin on ice. In the biosafety cabinet, the cord will be washed with 4-5
      changes of sterile 1x PBS and placed in a Petri plate with 15 ml PBS. The cord will be gently
      scraped with a surgical blade to remove any dead cells. A 9 cm umbilical cord will be cut
      into three equal pieces and wash thoroughly to remove blood clots, umbilical cord arteries,
      and veins. Segments will be washed three times with PBS and minced. The minced pieces will be
      incubated in 17.5 ml of collagenase solution (201 U/ml collagenase type I in serum-free
      DMEM-HG) in a 50 ml conical tube for ~3.5 hours in an incubator at 5% CO2, 95% humidity at
      37⁰C. After ~3.5 hours, the digested lysate will pass through a strainer and will be diluted
      three times with 1x PBS. Following centrifugation, the cells will be seeded into two 25 cm2
      flasks and will be placed in an incubator at 5% CO2, 95% humidity at 37⁰C. The flasks will be
      fed with fresh media (DMEM-HG supplemented with 20% FBS and 1% antibiotic solution) every
      third day. At around day 18, cells will reach up to 85% confluency and will be transferred in
      two 75 cm2 flasks with media replaced at alternate days. UCMSCs at P3 will be characterized
      using different specific antibodies. Cells at P3 will be used for transplantation in
      patients. Fifteen (15) subjects will be treated with three intravenous infusions (IV) of
      500,000 UCMSCs per Kg body weight delivered via peripheral intravenous infusion.
    

Intervention name(s): Intravenous Infusions of Stem Cells
Intervention type(s): Biological
Intervention description(s): Cultured stem cells will be injected at days 1, 3 and 5 intravenously. While patients will be monitored and evaluated for various hematological and organ functions at baseline (day 0) and days 1, 3, 5, 7, 14, 21 and 30
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Group 1 (15 subjects) Fifteen (15) subjects will be treated with three intravenous infusion (IV) of 5 x 10^5 (per Kg body weight) UCMSCs delivered via peripheral intravenous infusion on days 1, 3 and 5 besides the standard care (SOC).
Group 2 (5 subjects) Five (5) subjects will be treated under SOC. From two subjects in group 1 will not be treated 24hrs apart. Patients will be randomized in a 1:3 ratio (SOC: UCMSC).
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: COVID-19; Stem Cells treatment