Use of UC-MSCs for COVID-19 Patients

Sponsor

Camillo Ricordi (Other)

Overall Status

Completed

CT.gov ID

NCT04355728

Collaborator

(none)

Enrollment

Location

Arms

6.2

Actual Duration (Months)

3.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this research study is to learn about the safety and efficacy of human umbilical cord derived Mesenchymal Stem Cells (UC-MSC) for treatment of COVID-19 Patients with Severe Complications of Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS).

Condition or Disease	Intervention/Treatment	Phase
Corona Virus Infection ARDS ARDS, Human Acute Respiratory Distress Syndrome COVID-19	Biological: Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care. Other: Vehicle + Heparin along with best supportive care	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

The trial has two groups, each with 12 subjects (n=24). All eligible subjects will be randomized to either the treatment group or standard of care, and randomization will be stratified by ARDS severity.The trial has two groups, each with 12 subjects (n=24). All eligible subjects will be randomized to either the treatment group or standard of care, and randomization will be stratified by ARDS severity.

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

Double-Blinding Trial

Primary Purpose:

Treatment

Official Title:

Umbilical Cord-derived Mesenchymal Stem Cells for COVID-19 Patients With Acute Respiratory Distress Syndrome (ARDS)

Actual Study Start Date :

Apr 25, 2020

Actual Primary Completion Date :

Oct 31, 2020

Actual Study Completion Date :

Oct 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: UC-MSCs Group Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment.	Biological: Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care. UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.
Placebo Comparator: Control Group Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment.	Other: Vehicle + Heparin along with best supportive care Best supportive care treatment per the treating hospital protocol.

Arm

Intervention/Treatment

Experimental: UC-MSCs Group

Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment.

Biological: Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.

UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.

Placebo Comparator: Control Group

Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment.

Other: Vehicle + Heparin along with best supportive care

Best supportive care treatment per the treating hospital protocol.

Outcome Measures

Primary Outcome Measures

Number of Participants With Pre-Specified Infusion Associated Adverse Events [6 and 24 hours]
Safety as defined by the number of pre-specified infusion associated adverse events as assessed by treating physician. Any of the following occurring within 6 h post each infusion: An increase in vasopressor dose greater than or equal to the following: Norepinephrine: 10 μg/min Phenylephrine: 100 μg/min Dopamine: 10 μg/kg/min Epinephrine: 10 μg/min In patients receiving mechanical ventilation: worsening hypoxemia, as assessed by a requirement for an increase of PEEP by 5 cm H2O over baseline, or requirement to increase FiO2 of >20%. In patients receiving high flow oxygen therapy: worsening hypoxemia, as indicated by requirement of intubation and mechanical ventilation. New cardiac arrhythmia requiring cardioversion New ventricular tachycardia, ventricular fibrillation, or asystole A clinical scenario consistent with transfusion incompatibility or transfusion-related infection Cardiac arrest or death within 24h post infusion
Number of Subjects With Serious Adverse Events by 31 Days After First Infusion [31 days]
The number of subjects experiencing serious adverse events by 31 days after the first infusion (corresponding to 28 days after the last infusion).
Percentage of Participants Experiencing Serious Adverse Events (SAEs) Through Study Day 90 [90 days]
Safety will be reported as the percentage of participants experiencing serious adverse events through Day 90 as assessed by treating physician.
Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) [90 days]
Total number of adverse events and serious adverse events as assessed by treating physician
Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) by Severity [90 days]
Total number of adverse events plus serious adverse events categorized by severity.
Subjects With Adverse Events and Serious Adverse Events by Severity [90 days]
Total number of subjects with adverse events and serious adverse events categorized by severity.
Number of Adverse Events and Serious Adverse Events by Relatedness to Treatment [90 days]
Total number of adverse events and serious adverse events categorized by relatedness to treatment defined by a medical professional.
Subjects With Adverse Events by Relatedness to Treatment [90 days]
Total number of subjects with adverse events categorized by relatedness to treatment by a medical professional

Secondary Outcome Measures

Survival at 31 Days Post First Infusion [31 Days]
Number of participants that are alive at 31 days post first infusion follow up corresponding to 28 day post second infusion.
Survival at 60 Days Post First Infusion [60 days]
Number of participants alive at 60 days post first infusion follow up.
Time to Recovery [31 days]
Time to discharge or, if the subject was hospitalized, no longer requiring supplemental oxygen and no longer requiring COVID-19-related medical care by 31 days. The numbers represent days at which 25%, 50%, 75% subjects within the treatment group had recovered.
Ventilator-Free Days Throughout 28 Days Post Second Infusion [28 days post second infusion]
Number of days participants were off ventilators during 28 days post second infusion.
Ventilator-Free Days Throughout 90 Days [90 days or hospital discharge, whichever is earlier]
Number of days participants were off ventilators within up to 90 days of hospitalization.
Respiratory Rate and Oxygenation Index (ROX Index) [day 6]
Respiratory Rate-Oxygenation (ROX) index is defined as the ratio of oxygen saturation as measured by pulse oximetry (SpO2)/ Fraction of inspired oxygen (FiO2) to respiratory rate. This index can be used in the assessment of disease progression and the risk of intubation in COVID-19 patients with pneumonia.
Oxygenation Index (OI) [day 6]
Measure of the fraction of inspired oxygen (FiO2) and its usage within the body during intensive care, measured using fNIRS (Functional Near Infrared Spectroscopy). The calculation for Oxygenation index is ((FIO2 * Mean airway pressure)/partial pressure of oxygen).
Positive End-Expiratory Pressure (PEEP) and Plateau Pressure (Pplat) [day 6]
Measuring the respiratory mechanics; positive end-expiratory pressure (PEEP) and plateau pressure (Pplat) in ventilated patients visit 8 (day 6)
Sequential Organ Failure Assessment (SOFA) Scores [Day 6]
Sequential Organ Failure Assessment (SOFA) Scores is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from a minimum of 0 (normal) to a maximum of 4 (high degree of dysfunction/failure). The total score corresponds to the sum of the six different scores of the organ systems. In total, the minimum SOFA score is 0 (normal) and the maximum SOFA score is 24 (highest degree dysfunction/failure).
Smell Identification Test (SIT) Scores [90 days]
SIT measures the participant's sense of smell. SIT has a total score ranging from 0 to 40 with the higher the score indicating a more normal sense of smell
White Blood Cell Count (WBC) [day 6]
As assessed via serum blood samples.
Platelets Count [day 6]
As assessed via serum blood samples.
Hemogoblin [day 6]
Measures the total amount of the oxygen-carrying protein in the blood as assessed via serum blood samples.
Hematocrit [day 6]
The percentage by volume of red cells in your blood as assessed via serum blood samples.
Neutrophils [day 6]
the amount of immune cells (that is one of the first cell types to travel to the site of an infection) as assessed via serum blood samples
Lymphocytes [day 6]
Lymphocyte count as assessed via serum blood samples
Glomerular Filtration Rate [day 6]
Glomerular filtration rate (GFR) as assessed via serum blood samples to check how well the kidneys are working. It estimates how much blood passes through the glomeruli each minute.
Total Protein [Day 6]
Total protein as assessed via serum blood samples as a part of the comprehensive metabolic panel (CMP). It is a measurement of the sum of albumin and globulins.
Sodium [day 6]
Sodium levels as assessed by serum blood samples.
Potassium [day 6]
Potassium levels as assessed via serum blood samples.
Creatinine [day 6]
Creatinine levels as assessed via serum blood samples
Glucose [day 6]
Glucose levels as assessed via serum blood samples
Albumin [day 6]
Albumin levels as assessed via serum blood samples
Alkaline Phosphatase [day 6]
Alkaline phosphatase levels as assessed via serum blood samples for the Comprehensive Metabolic Panel.
Alanine Aminotransferase or Serum Glutamate-pyruvate Transaminase (ALT or SGPT) [day 6]
The alanine aminotransferase or serum glutamate-pyruvate transaminase (ALT or SGPT) test as assessed via serum blood samples
Aspartate Aminotransferase or Serum Glutamic Oxaloacetic Transaminase (AST or SGOT) [day 6]
The aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST or SGOT) test as assessed via serum blood samples
Total Bilirubin [day 6]
Bilirubin levels as assessed via serum blood samples for the comprehensive metabolic panel.
Blood Urea Nitrogen (BUN) [day 6]
Blood urea nitrogen (BUN) levels as assessed via serum blood samples for the comprehensive metabolic panel.
Calcium [day 6]
Calcium levels as assessed via serum blood samples for the comprehensive metabolic panel.
Chloride [day 6]
Chloride levels as assessed via serum blood samples for the comprehensive metabolic panel.
Carbon Dioxide (CO2) [day 6]
Carbon Dioxide (CO2) levels as assessed via serum blood samples for the comprehensive metabolic panel.
C-Reactive Protein Levels [day 6]
As assessed via serum blood samples.
Arachidonic Acid/Eicosapentaenoic Acid (AA/EPA) Ratio [day 6]
As assessed via serum blood samples on day 6 (visit 8).
D-dimer Levels [day 6]
As assessed via serum blood samples.
25-Hydroxy Vitamin D Levels [day 6]
As assessed via serum blood samples.
Tumor Necrosis Factor-alpha (TNFα) [day 6]
Analysis of TNFα in peripheral blood plasma
Tumor Necrosis Factor-beta (TNFβ) [day 6]
Analysis of TNFβ in peripheral blood plasma
Soluble Tumor Necrosis Factor Receptor 2 (sTNFR2) [day 6]
Analysis of soluble tumor necrosis factor receptor 2 (sTNFR2) in peripheral blood plasma
Viral Load by SARS-CoV-2 RT-PCR [day 6]
Viral load as assessed in blood plasma for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) via Reverse Transcriptase Polymerase Chain Reaction (RT-PCR).
Number of Participants Reporting Panel Reactive Antibody (PRA) Positivity at Day 3 Post First Infusion [day 3 post first infusion]
Number of participants reporting panel reactive antibody (PRA) positivity at Day 3 post first infusion for class I and class II as assessed via serum blood samples. These antibodies can develop following a transplant. Recipients can become sensitized to certain molecules (Human Leukocyte Antigen Class I or Class II), which can affect immune responses to and rejection of potential future transplants.
Number of Participants Reporting Panel Reactive Antibody (PRA) Positivity at Day 6 Post First Infusion [day 6]
Number of participants reporting panel reactive antibody (PRA) positivity at Day 6 post first infusion for class I and class II as assessed via serum blood samples. These antibodies can develop following a transplant. Recipients can become sensitized to certain molecules (Human Leukocyte Antigen Class I or Class II), which can affect immune responses to and rejection of potential future transplants.
Number of Participants Reporting Panel Reactive Antibody (PRA) Positivity at Day 14 Post First Infusion [day 14]
Number of participants reporting panel reactive antibody (PRA) positivity at Day 14 post first infusion for class I and class II as assessed via serum blood samples. These antibodies can develop following a transplant. Recipients can become sensitized to certain molecules (Human Leukocyte Antigen Class I or Class II), which can affect immune responses to and rejection of potential future transplants.
Number of Participants With Positive, Negative, or Borderline Serology Testing for SARS-CoV-2 IgM/IgG [day 14 post first infusion]
Number of participants with positive, negative, or borderline SARS-CoV-2 Immunoglobulin M (IgM)/Immunoglobulin G (IgG) serology from serum blood samples.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients >/= 18 years old diagnosed with COVID-19 (as evaluated by PCR test confirming infection with SARS-CoV-2) will be eligible for inclusion if they meet all of the below criteria. Inclusion criteria must all be present within a 24-hour time period at the time of enrollment:

Patient currently hospitalized
Aged ≥ 18 years
Willing and able to provide written informed consent, or with a legal representative who can provide informed consent
Peripheral capillary oxygen saturation (SpO2) ≤ 94% at room air, or requiring supplemental oxygen at screening
PaO2/FiO2 ratio < 300 mmHg
Bilateral infiltrates on frontal chest radiograph or bilateral ground glass opacities on a chest CT scan
Hypoxemia requiring an increase in the fraction of inspired oxygen (FiO2) of ≥ 20% AND an increase in positive end-expiratory airway pressure (PEEP) level of 5 cm H2O or more to maintain transcutaneous oxygen saturations in the target range of 88-95%, or requirement for escalation from oxygen therapy to invasive mechanical ventilation

Exclusion Criteria:

PaO2/FiO2 ≥ 300 at the time of enrollment
A previous MSC infusion not related to this trial
History of Pulmonary Hypertension (WHO Class III/IV)
History of left atrial hypertension or decompensated left heart failure.
Pregnant or lactating patient
Unstable arrhythmia
Patients with previous lung transplant
Patients currently receiving chronic dialysis
Patients currently receiving Extracorporeal Membrane Oxygenation (ECMO)
Presence of any active malignancy (except non-melanoma skin cancer)
Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
Moderate to severe liver disease (AST and ALT >5 X ULN)
Severe chronic respiratory disease with a PaCO2 > 50 mm Hg or the use of home oxygen
Baseline QT prolongation
Moribund patient not expected to survive > 24 hours

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Diabetes Research Institute, University of Miami Miller School of Medicine	Miami	Florida	United States	33136

Sponsors and Collaborators

Camillo Ricordi

Investigators

Principal Investigator: Camillo Ricordi, MD, University of Miami

Study Documents (Full-Text)

Study Protocol and Statistical Analysis Plan - Feb 12, 2021

More Information

Publications

None provided.

Responsible Party:

Camillo Ricordi, Professor of Surgery and Chief, Division of Cellular Transplantation, University of Miami

ClinicalTrials.gov Identifier:

NCT04355728

Other Study ID Numbers:

20200671
20200370

First Posted:

Apr 21, 2020

Last Update Posted:

Dec 6, 2021

Last Verified:

Dec 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Camillo Ricordi, Professor of Surgery and Chief, Division of Cellular Transplantation, University of Miami

COVID-19

Additional relevant MeSH terms:

COVID-19

Coronavirus Infections

Respiratory Distress Syndrome

Respiratory Distress Syndrome, Newborn

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Period Title: Overall Study
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	UC-MSCs Group	Control Group	Total
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.	Total of all reporting groups
Overall Participants	12	12	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 66.7%	7 58.3%	15 62.5%
>=65 years	4 33.3%	5 41.7%	9 37.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.58 (15.93)	58.83 (11.61)	58.71 (13.63)
Sex: Female, Male (Count of Participants)
Female	7 58.3%	4 33.3%	11 45.8%
Male	5 41.7%	8 66.7%	13 54.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 91.7%	11 91.7%	22 91.7%
Not Hispanic or Latino	1 8.3%	1 8.3%	2 8.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 8.3%	2 16.7%	3 12.5%
White	11 91.7%	10 83.3%	21 87.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	12 100%	12 100%	24 100%
Hemogoblin from Complete Blood Count (g/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/dL]	12.93 (2.04)	12.45 (2.35)	12.69 (2.17)
Hematocrit from Complete Blood Count (percentage of total blood volume) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of total blood volume]	39.71 (6.53)	40.76 (5.08)	40.18 (5.79)
White Blood Count (WBC) from Complete Blood Count (10^3 cells/uL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [10^3 cells/uL]	11.87 (5.26)	14.17 (5.45)	13.02 (5.37)
Neutrophils from Complete Blood Count (10^3 cells/uL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [10^3 cells/uL]	9.25 (4.8)	13.37 (5.33)	11.21 (5.36)
Lymphocytes from Complete Blood Count (10^3 cells/uL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [10^3 cells/uL]	1.15 (0.79)	0.72 (0.25)	0.95 (0.62)
Platelet count from Complete Blood Count (10^3 cells/uL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [10^3 cells/uL]	329.83 (99.52)	342.58 (91.83)	336.21 (93.88)
Glomerular Filtration Rate from Comprehensive Metabolic Panel (mL/min/1.73 m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min/1.73 m^2]	74.5 (31.61)	61.25 (37.59)	67.88 (34.63)
Total Protein from Comprehensive Metabolic Panel (g/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/dL]	6.39 (0.69)	6.45 (0.68)	6.42 (0.67)
Sodium for Comprehensive Metabolic Panel (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	138.92 (3.15)	136.58 (5.04)	137.75 (4.28)
Potassium for Comprehensive Metabolic Panel (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	4.37 (0.55)	4.52 (0.67)	4.44 (0.6)
Creatine for Comprehensive Metabolic Panel (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	1.18 (0.77)	1.92 (1.88)	1.55 (1.46)
Glucose for Comprehensive Metabolic Panel (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	190.75 (107.14)	193.67 (85.44)	192.21 (94.78)
Albumin for Comprehensive Metabolic Panel (g/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/dL]	3.22 (0.39)	3.21 (0.51)	3.22 (0.44)
Alkaline Phosphatase for Comprehensive Metabolic Panel (U/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [U/L]	90.9 (59.3)	96.5 (52.69)	93.7 (54.67)
Alanine Aminotransferase (ALT) or Serum Glutamic-pyruvic Transaminase (SGPT) (U/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [U/L]	72.1 (51.19)	82.45 (75.18)	77.52 (63.51)
Aspartate Aminotransferase (AST) or Serum Glutamic-Oxaloacetic Transaminase (SGOT) (U/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [U/L]	55.8 (31.07)	118.45 (153.16)	88.62 (114.86)
Total Bilirubin for Comprehensive Metabolic Panel (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	0.62 (0.39)	0.65 (0.25)	0.64 (0.32)
Blood Urea Nitrogen (BUN) for Comprehensive Metabolic Panel (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	29.58 (16.61)	42.67 (31.27)	36.13 (25.38)
Calcium for Comprehensive Metabolic Panel (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	8.53 (0.4)	8.32 (0.87)	8.43 (0.67)
Chloride Comprehensive Metabolic Panel (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	101 (4.29)	100.5 (6.33)	100.75 (5.29)
Carbon Dioxide (CO2) for Comprehensive Metabolic Panel (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	24.42 (3.99)	21.92 (4.62)	23.17 (4.41)
Oxygenation Index (Index) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Index]	8.09 (2.63)	14.32 (14.68)	11.83 (11.5)
Positive End-Expiratory Pressure (PEEP) (cm H2O) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm H2O]	13.75 (2.06)	12.71 (2.14)	13.09 (2.07)
Plateau Pressure (cm H2O) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm H2O]	13.75 (9.74)	29 (7.39)	21.38 (11.43)
Sequential Organ Failure Assessment (SOFA) Score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	5.5 (2.61)	7.64 (3.35)	6.52 (3.12)
C-Reactive Protein (CRP) (mg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/L]	97.97 (77.56)	144.35 (115.69)	121.16 (99.19)
D-Dimer (mcg/mL FEU) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mcg/mL FEU]	1.76 (2.35)	4.96 (6.04)	3.29 (4.69)
Arachidonic Acid/Eicosapentaenoic Acid (AA/EPA) Ratio (ratio of AA to EPA) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ratio of AA to EPA]	45.38 (24.89)	45.79 (23.93)	45.58 (23.88)
25-OH vitamin D levels (ng/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/ml]	21.76 (8.48)	23.19 (12.85)	22.47 (10.68)
Respiratory Rate and Oxygenation Index (ROX) (Index) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Index]	7.36 (7.73)	3.59 (1.13)	5.91 (6.24)
Viral Load by SARS-CoV-2 RT-PCR (copies) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [copies]	352	3570.50	710
Panel Reactive Antibody (PRA) (Count of Participants)
Positive PRA	11 91.7%	9 75%	20 83.3%
Negative PRA	1 8.3%	3 25%	4 16.7%
Positive PRA	4 33.3%	6 50%	10 41.7%
Negative PRA	8 66.7%	6 50%	14 58.3%
Serology (anti-SARS-CoV-2 IgM and IgG) (Count of Participants)
Positive	4 33.3%	5 41.7%	9 37.5%
Negative	6 50%	2 16.7%	8 33.3%
Borderline	0 0%	2 16.7%	2 8.3%
Positive	5 41.7%	8 66.7%	13 54.2%
Negative	4 33.3%	1 8.3%	5 20.8%
Borderline	1 8.3%	0 0%	1 4.2%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Pre-Specified Infusion Associated Adverse Events
Description	Safety as defined by the number of pre-specified infusion associated adverse events as assessed by treating physician. Any of the following occurring within 6 h post each infusion: An increase in vasopressor dose greater than or equal to the following: Norepinephrine: 10 μg/min Phenylephrine: 100 μg/min Dopamine: 10 μg/kg/min Epinephrine: 10 μg/min In patients receiving mechanical ventilation: worsening hypoxemia, as assessed by a requirement for an increase of PEEP by 5 cm H2O over baseline, or requirement to increase FiO2 of >20%. In patients receiving high flow oxygen therapy: worsening hypoxemia, as indicated by requirement of intubation and mechanical ventilation. New cardiac arrhythmia requiring cardioversion New ventricular tachycardia, ventricular fibrillation, or asystole A clinical scenario consistent with transfusion incompatibility or transfusion-related infection Cardiac arrest or death within 24h post infusion
Time Frame	6 and 24 hours

Outcome Measure Data

Analysis Population Description
In the UC-MSC treatment group, 4 participants were on mechanical ventilation and 8 participants were receiving high flow oxygen therapy. In the control group 7 participants were on mechanical ventilation and 5 participants were receiving high flow oxygen therapy.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	12	12
Number of subjects with an increase in vasopressor dose at 6 h	1 8.3%	1 8.3%
In subjects receiving mechanical ventilation, Number of subjects with worsening of hypoxemia at 6 h	1 8.3%	1 8.3%
In subjects on high flow oxygen therapy:worsening hypoxemia(req intubat, mechanical ventilat) at 6 h	0 0%	0 0%
Number of subjects with new cardiac arrhythmia requiring cardioversion at 6 h	0 0%	1 8.3%
Number of subjects with new ventricular tachycardia, ventricular fibrillation, or asystole at 6 h	0 0%	1 8.3%
A clinical scenario consistent with transfusion incompatibility or transfusion-rel infection at 6h	0 0%	0 0%
Number of subjects with cardiac arrest or death within 24 h post infusion	0 0%	0 0%

2. Primary Outcome

Title	Number of Subjects With Serious Adverse Events by 31 Days After First Infusion
Description	The number of subjects experiencing serious adverse events by 31 days after the first infusion (corresponding to 28 days after the last infusion).
Time Frame	31 days

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	12	12
Count of Participants [Participants]	2 16.7%	8 66.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UC-MSCs Group, Control Group
	Comments	The null hypothesis is the following: "There is no difference in the number of subjects experiencing serious adverse events in the UC-MSC vs control group".
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	.04
	Comments
	Method	Fisher Exact
	Comments

3. Primary Outcome

Title	Percentage of Participants Experiencing Serious Adverse Events (SAEs) Through Study Day 90
Description	Safety will be reported as the percentage of participants experiencing serious adverse events through Day 90 as assessed by treating physician.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	12	12
Number [percentage of participants]	41.67 347.3%	66.67 555.6%

4. Primary Outcome

Title	Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	Total number of adverse events and serious adverse events as assessed by treating physician
Time Frame	90 days

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	12	12
Number of Adverse Events (not including SAEs)	40	37
Number of Serious Adverse Events	6	16

5. Primary Outcome

Title	Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) by Severity
Description	Total number of adverse events plus serious adverse events categorized by severity.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	12	12
Mild	15	13
Moderate	22	21
Severe	9	19

6. Primary Outcome

Title	Subjects With Adverse Events and Serious Adverse Events by Severity
Description	Total number of subjects with adverse events and serious adverse events categorized by severity.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description
Subjects who experience one or more AEs or SAEs within each category are counted only once.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	12	12
Mild	7 58.3%	5 41.7%
Moderate	7 58.3%	8 66.7%
Severe	5 41.7%	7 58.3%

7. Primary Outcome

Title	Number of Adverse Events and Serious Adverse Events by Relatedness to Treatment
Description	Total number of adverse events and serious adverse events categorized by relatedness to treatment defined by a medical professional.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	12	12
Unrelated	42	45
Unlikely	3	7
Possible	1	1
Probably	0	0
Definite	0	0

8. Primary Outcome

Title	Subjects With Adverse Events by Relatedness to Treatment
Description	Total number of subjects with adverse events categorized by relatedness to treatment by a medical professional
Time Frame	90 days

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	12	12
Unrelated	8 66.7%	10 83.3%
Unlikely	1 8.3%	4 33.3%
Possible	1 8.3%	1 8.3%
Probable	0 0%	0 0%
Defininte	0 0%	0 0%

9. Secondary Outcome

Title	Survival at 31 Days Post First Infusion
Description	Number of participants that are alive at 31 days post first infusion follow up corresponding to 28 day post second infusion.
Time Frame	31 Days

Outcome Measure Data

Analysis Population Description
One subject in the UC-MSC Group was not included in the data analysis due to failed intubation.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	11	12
Count of Participants [Participants]	10 83.3%	5 41.7%

10. Secondary Outcome

Title	Survival at 60 Days Post First Infusion
Description	Number of participants alive at 60 days post first infusion follow up.
Time Frame	60 days

Outcome Measure Data

Analysis Population Description
A subject was censored due to failed intubation in the UC-MSC group.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	11	12
Count of Participants [Participants]	9 75%	5 41.7%

11. Secondary Outcome

Title	Time to Recovery
Description	Time to discharge or, if the subject was hospitalized, no longer requiring supplemental oxygen and no longer requiring COVID-19-related medical care by 31 days. The numbers represent days at which 25%, 50%, 75% subjects within the treatment group had recovered.
Time Frame	31 days

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	12	12
Days by which 75% of subjects were recovered	23	NA
Days by which 50% of subjects were recovered	15	NA
Days by which 25% of subjects were recovered	8	12

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UC-MSCs Group, Control Group
	Comments	The null hypothesis is the following: "There is no difference in Time to Recovery up to 31 days post infusion between the UC-MSC group and control group". Time to recovery was estimated in each group with Kaplan-Meier survival estimates. Log-rank tests were used to compare hazards between groups.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0307
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.289
	Confidence Interval	(2-Sided) 95% 0.088 to 0.948
	Parameter Dispersion	Type: Value:
	Estimation Comments	Censoring was limited to dropout from study, and the event of interest was recovery. In the case of death, the patient's time to recovery was censored at the end of study observation; thus the patient remained in the risk set for all KM estimations.

12. Secondary Outcome

Title	Ventilator-Free Days Throughout 28 Days Post Second Infusion
Description	Number of days participants were off ventilators during 28 days post second infusion.
Time Frame	28 days post second infusion

Outcome Measure Data

Analysis Population Description
In the UC-MSC treatment group one subject was not included in the analysis due to censoring and another subject was not included due to loss to follow-up. In the control group one subject was not included in the analysis due to discharge against medical advice.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	10	11
Median (Inter-Quartile Range) [days]	28	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UC-MSCs Group, Control Group
	Comments	Null Hypothesis: The center of the distributions of ventilator free days are equal in the UC-MSC and control group.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	.0563
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

13. Secondary Outcome

Title	Ventilator-Free Days Throughout 90 Days
Description	Number of days participants were off ventilators within up to 90 days of hospitalization.
Time Frame	90 days or hospital discharge, whichever is earlier

Outcome Measure Data

Analysis Population Description
In the UC-MSC treatment group one subject was not included in the analysis due to censoring and another subject was not included due to loss to follow-up. In the control group one subject was not included in the analysis due to discharge against medical advice.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	10	11
Median (Inter-Quartile Range) [days]	90	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UC-MSCs Group, Control Group
	Comments	Null Hypothesis: The center of the distributions of ventilator free days are equal in the UC-MSC and control group.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	.0563
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

14. Secondary Outcome

Title	Respiratory Rate and Oxygenation Index (ROX Index)
Description	Respiratory Rate-Oxygenation (ROX) index is defined as the ratio of oxygen saturation as measured by pulse oximetry (SpO2)/ Fraction of inspired oxygen (FiO2) to respiratory rate. This index can be used in the assessment of disease progression and the risk of intubation in COVID-19 patients with pneumonia.
Time Frame	day 6

Outcome Measure Data

Analysis Population Description

ROX index was only measured for patients receiving HFNC and/or not intubated patients. Three patients were ventilated in the UC-MSC group, one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, two patients data was not collected. In the control group one subject was not included in the analysis due to death before day 6, three patients were ventilated, and one patient data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	5	7
Mean (Standard Deviation) [Index]	9.57 (5.23)	7.44 (2.9)

15. Secondary Outcome

Title	Oxygenation Index (OI)
Description	Measure of the fraction of inspired oxygen (FiO2) and its usage within the body during intensive care, measured using fNIRS (Functional Near Infrared Spectroscopy). The calculation for Oxygenation index is ((FIO2 * Mean airway pressure)/partial pressure of oxygen).
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
Oxidation Index is only measured and calculated in ventilated patients, therefore 3 patients in the UC-MSC group were included and 3 patients in the control group were included.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	3	3
Mean (Standard Deviation) [Index]	9.62 (1.43)	12.74 (5.21)

16. Secondary Outcome

Title	Positive End-Expiratory Pressure (PEEP) and Plateau Pressure (Pplat)
Description	Measuring the respiratory mechanics; positive end-expiratory pressure (PEEP) and plateau pressure (Pplat) in ventilated patients visit 8 (day 6)
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
PEEP and Plateau pressure are only measured in ventilated patients, therefore 3 patients in the UC-MSC group were included and 3 patients in the control group were included.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	3	3
PEEP	9.73 (3.72)	11.67 (1.53)
Plateau Pressure	28.67 (9.61)	24 (2.83)

17. Secondary Outcome

Title	Sequential Organ Failure Assessment (SOFA) Scores
Description	Sequential Organ Failure Assessment (SOFA) Scores is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from a minimum of 0 (normal) to a maximum of 4 (high degree of dysfunction/failure). The total score corresponds to the sum of the six different scores of the organ systems. In total, the minimum SOFA score is 0 (normal) and the maximum SOFA score is 24 (highest degree dysfunction/failure).
Time Frame	Day 6

Outcome Measure Data

Analysis Population Description
In the UC-MSC treatment group one subject was not included in the analysis due to death and 2 subjects were not included due to discharge on day 6. In the control group one subject was not included in the analysis due to death before day 6.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	9	11
Mean (Standard Deviation) [score on a scale]	6.56 (2.7)	6.82 (2.36)

18. Secondary Outcome

Title	Smell Identification Test (SIT) Scores
Description	SIT measures the participant's sense of smell. SIT has a total score ranging from 0 to 40 with the higher the score indicating a more normal sense of smell
Time Frame	90 days

Outcome Measure Data

Analysis Population Description
No participants in the study were able to complete the Smell Evaluation Test due to extenuating circumstances related to the COVID-19 pandemic.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	0	0

19. Secondary Outcome

Title	White Blood Cell Count (WBC)
Description	As assessed via serum blood samples.
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and one subject data was not collected. In the control group one subject was not included in the analysis due to death before day 6, two subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	9	9
Mean (Standard Deviation) [10^3 cells/uL]	13.43 (4.62)	15.53 (5.6)

20. Secondary Outcome

Title	Platelets Count
Description	As assessed via serum blood samples.
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and one subject data was not collected. In the control group one subject was not included in the analysis due to death before day 6, two subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	9	9
Mean (Standard Deviation) [10^3 cells/uL]	342 (136.33)	397.89 (135.59)

21. Secondary Outcome

Title	Hemogoblin
Description	Measures the total amount of the oxygen-carrying protein in the blood as assessed via serum blood samples.
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and one subject data was not collected. In the control group one subject was not included in the analysis due to death before day 6, two subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	9	9
Mean (Standard Deviation) [g/dL]	11.93 (2.82)	11.94 (3.34)

22. Secondary Outcome

Title	Hematocrit
Description	The percentage by volume of red cells in your blood as assessed via serum blood samples.
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and one subject data was not collected. In the control group one subject was not included in the analysis due to death before day 6, two subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	9	9
Mean (Standard Deviation) [percentage of red blood cells by volume]	37.98 (8.32)	36.73 (9.56)

23. Secondary Outcome

Title	Neutrophils
Description	the amount of immune cells (that is one of the first cell types to travel to the site of an infection) as assessed via serum blood samples
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and two subjects data was not collected. In the control group one subject was not included in the analysis due to death before day 6, two subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	8	9
Mean (Standard Deviation) [10^3 cells/uL]	9.74 (4.27)	13.4 (5.95)

24. Secondary Outcome

Title	Lymphocytes
Description	Lymphocyte count as assessed via serum blood samples
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and two subjects data was not collected. In the control group one subject was not included in the analysis due to death before day 6, two subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	8	9
Mean (Standard Deviation) [10^3 cells/uL]	1.38 (1.07)	0.8 (0.41)

25. Secondary Outcome

Title	Glomerular Filtration Rate
Description	Glomerular filtration rate (GFR) as assessed via serum blood samples to check how well the kidneys are working. It estimates how much blood passes through the glomeruli each minute.
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and one subject data was not collected. In the control group one subject was not included in the analysis due to death before day 6, two subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	9	9
Mean (Standard Deviation) [mL/min/1.73 m^2]	60.59 (26.99)	68.67 (35.4)

26. Secondary Outcome

Title	Total Protein
Description	Total protein as assessed via serum blood samples as a part of the comprehensive metabolic panel (CMP). It is a measurement of the sum of albumin and globulins.
Time Frame	Day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and 5 subjects data was not collected. In the control group one subject was not included in the analysis due to death before day 6, and 5 subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	5	6
Mean (Standard Deviation) [g/dL]	5.88 (0.54)	5.8 (1.06)

27. Secondary Outcome

Title	Sodium
Description	Sodium levels as assessed by serum blood samples.
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and one subject data was not collected. In the control group one subject was not included in the analysis due to death before day 6, two subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	9	9
Mean (Standard Deviation) [mmol/L]	141.22 (6.24)	141 (9.57)

28. Secondary Outcome

Title	Potassium
Description	Potassium levels as assessed via serum blood samples.
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and one subject data was not collected. In the control group one subject was not included in the analysis due to death before day 6, two subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	9	9
Mean (Standard Deviation) [mmol/L]	4.25 (0.71)	4.37 (0.73)

29. Secondary Outcome

Title	Creatinine
Description	Creatinine levels as assessed via serum blood samples
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and one subject data was not collected. In the control group one subject was not included in the analysis due to death before day 6, two subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	9	9
Mean (Standard Deviation) [mg/dL]	1.21 (0.54)	1.24 (0.74)

30. Secondary Outcome

Title	Glucose
Description	Glucose levels as assessed via serum blood samples
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and one subject data was not collected. In the control group one subject was not included in the analysis due to death before day 6, two subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	9	9
Mean (Standard Deviation) [mg/dL]	153.11 (63.99)	183.89 (82.33)

31. Secondary Outcome

Title	Albumin
Description	Albumin levels as assessed via serum blood samples
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and 5 subjects data was not collected. In the control group one subject was not included in the analysis due to death before day 6, and 5 subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	5	6
Mean (Standard Deviation) [g/dL]	2.96 (0.43)	2.73 (0.45)

32. Secondary Outcome

Title	Alkaline Phosphatase
Description	Alkaline phosphatase levels as assessed via serum blood samples for the Comprehensive Metabolic Panel.
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and 5 subjects data was not collected. In the control group one subject was not included in the analysis due to death before day 6, and 5 subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	5	6
Mean (Standard Deviation) [U/L]	136.2 (68.36)	202.5 (219.13)

33. Secondary Outcome

Title	Alanine Aminotransferase or Serum Glutamate-pyruvate Transaminase (ALT or SGPT)
Description	The alanine aminotransferase or serum glutamate-pyruvate transaminase (ALT or SGPT) test as assessed via serum blood samples
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and 5 subjects data was not collected. In the control group one subject was not included in the analysis due to death before day 6, and 5 subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	5	6
Mean (Standard Deviation) [U/L]	64.4 (38.43)	65.67 (45.04)

34. Secondary Outcome

Title	Aspartate Aminotransferase or Serum Glutamic Oxaloacetic Transaminase (AST or SGOT)
Description	The aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST or SGOT) test as assessed via serum blood samples
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and 5 subjects data was not collected. In the control group one subject was not included in the analysis due to death before day 6, and 5 subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	5	6
Mean (Standard Deviation) [U/L]	55.8 (23.86)	47 (32.47)

35. Secondary Outcome

Title	Total Bilirubin
Description	Bilirubin levels as assessed via serum blood samples for the comprehensive metabolic panel.
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and 5 subjects data was not collected. In the control group one subject was not included in the analysis due to death before day 6, and 5 subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	5	6
Mean (Standard Deviation) [mg/dL]	0.88 (0.46)	0.77 (0.29)

36. Secondary Outcome

Title	Blood Urea Nitrogen (BUN)
Description	Blood urea nitrogen (BUN) levels as assessed via serum blood samples for the comprehensive metabolic panel.
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and one subject data was not collected. In the control group one subject was not included in the analysis due to death before day 6, two subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	9	9
Mean (Standard Deviation) [mg/dL]	48 (22.28)	47.67 (26.97)

37. Secondary Outcome

Title	Calcium
Description	Calcium levels as assessed via serum blood samples for the comprehensive metabolic panel.
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and one subject data was not collected. In the control group one subject was not included in the analysis due to death before day 6, two subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	9	9
Mean (Standard Deviation) [mg/dL]	8.5 (0.58)	8.27 (0.67)

38. Secondary Outcome

Title	Chloride
Description	Chloride levels as assessed via serum blood samples for the comprehensive metabolic panel.
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and one subject data was not collected. In the control group one subject was not included in the analysis due to death before day 6, two subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	9	9
Mean (Standard Deviation) [mmol/L]	101.56 (7.63)	102.44 (9.04)

39. Secondary Outcome

Title	Carbon Dioxide (CO2)
Description	Carbon Dioxide (CO2) levels as assessed via serum blood samples for the comprehensive metabolic panel.
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and one subject data was not collected. In the control group one subject was not included in the analysis due to death before day 6, two subjects data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	9	9
Mean (Standard Deviation) [mmol/L]	28.44 (3.75)	26.44 (4.61)

40. Secondary Outcome

Title	C-Reactive Protein Levels
Description	As assessed via serum blood samples.
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
In the UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and data was missing for two subjects. In the control group one subject was not included in the analysis due to death before day 6.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	8	11
Mean (Standard Deviation) [mg/L]	101.01 (131.05)	112.55 (104.7)

41. Secondary Outcome

Title	Arachidonic Acid/Eicosapentaenoic Acid (AA/EPA) Ratio
Description	As assessed via serum blood samples on day 6 (visit 8).
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6. In the control group one subject was not included in the analysis due to death before day 6.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	10	11
Mean (Standard Deviation) [ratio of AA to EPA]	33.6 (12)	34.64 (13.24)

42. Secondary Outcome

Title	D-dimer Levels
Description	As assessed via serum blood samples.
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6, and one subject data was not collected. In the control group one subject was not included in the analysis due to death before day 6 and one subject data was not collected.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	9	10
Mean (Standard Deviation) [mcg/ml FEU]	6.2 (11.29)	4.69 (3.38)

43. Secondary Outcome

Title	25-Hydroxy Vitamin D Levels
Description	As assessed via serum blood samples.
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6. In the control group one subject was not included in the analysis due to death before day 6.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	10	11
Mean (Standard Deviation) [ng/ml]	23.21 (8.91)	27.58 (16.38)

44. Secondary Outcome

Title	Tumor Necrosis Factor-alpha (TNFα)
Description	Analysis of TNFα in peripheral blood plasma
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
In the UC-MSC treatment group one subject was not included in the analysis due to failed intubation. In the control group one subject was not included in the analysis because of death before day 6 blood draw.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	11	11
Median (Inter-Quartile Range) [pg/mL]	349	451

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UC-MSCs Group, Control Group
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0356
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

45. Secondary Outcome

Title	Tumor Necrosis Factor-beta (TNFβ)
Description	Analysis of TNFβ in peripheral blood plasma
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
In the UC-MSC treatment group one subject was not included in the analysis due to failed intubation. In the control group one subject was not included in the analysis because of death before day 6 blood draw.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	11	11
Median (Inter-Quartile Range) [pg/mL]	829	1540

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UC-MSCs Group, Control Group
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0215
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

46. Secondary Outcome

Title	Soluble Tumor Necrosis Factor Receptor 2 (sTNFR2)
Description	Analysis of soluble tumor necrosis factor receptor 2 (sTNFR2) in peripheral blood plasma
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
In the UC-MSC treatment group one subject was not included in the analysis due to failed intubation. In the control group one subject was not included in the analysis because of death before day 6 blood draw and data was unavailable for two patients.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	11	9
Mean (Standard Deviation) [pg/mL]	26609.09 (3071.96)	23111.11 (3086.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UC-MSCs Group, Control Group
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0210
	Comments
	Method	t-test, 2 sided
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3498
	Confidence Interval	(2-Sided) 95% -6404.7 to -591.2
	Parameter Dispersion	Type: Standard Deviation Value: 3078.2
	Estimation Comments

47. Secondary Outcome

Title	Viral Load by SARS-CoV-2 RT-PCR
Description	Viral load as assessed in blood plasma for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) via Reverse Transcriptase Polymerase Chain Reaction (RT-PCR).
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
The UC-MSC treatment group one subject was not included in the analysis due to death, one subject was not included due to discharge on day 6. In the control group one subject was not included in the analysis due to death before day 6.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	10	11
Median (Inter-Quartile Range) [RNA copies/mL]	0	0

48. Secondary Outcome

Title	Number of Participants Reporting Panel Reactive Antibody (PRA) Positivity at Day 3 Post First Infusion
Description	Number of participants reporting panel reactive antibody (PRA) positivity at Day 3 post first infusion for class I and class II as assessed via serum blood samples. These antibodies can develop following a transplant. Recipients can become sensitized to certain molecules (Human Leukocyte Antigen Class I or Class II), which can affect immune responses to and rejection of potential future transplants.
Time Frame	day 3 post first infusion

Outcome Measure Data

Analysis Population Description
One subject in the control group died before day 3 post first infusion.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	12	11
PRA Positive	10 83.3%	11 91.7%
PRA Negative	2 16.7%	0 0%
PRA Positive	4 33.3%	6 50%
PRA Negative	8 66.7%	5 41.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UC-MSCs Group, Control Group
	Comments	The null hypothesis is the following: "There is no association between PRA (class I) status and treatment group at 3 days post first infusion".
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	UC-MSCs Group, Control Group
	Comments	The null hypothesis is the following: "There is no association between PRA (class II) status and treatment group at 3 days post first infusion."
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.41
	Comments
	Method	Fisher Exact
	Comments

49. Secondary Outcome

Title	Number of Participants Reporting Panel Reactive Antibody (PRA) Positivity at Day 6 Post First Infusion
Description	Number of participants reporting panel reactive antibody (PRA) positivity at Day 6 post first infusion for class I and class II as assessed via serum blood samples. These antibodies can develop following a transplant. Recipients can become sensitized to certain molecules (Human Leukocyte Antigen Class I or Class II), which can affect immune responses to and rejection of potential future transplants.
Time Frame	day 6

Outcome Measure Data

Analysis Population Description
In the UC-MSC group one patient was censored and died before day 6 and one patient recovered before day 6 and left the hospital. In the control group on patient died before day 6 post first infusion.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	10	11
PRA Positive	9 75%	9 75%
PRA Negative	1 8.3%	2 16.7%
PRA Positive	5 41.7%	5 41.7%
PRA Negative	5 41.7%	6 50%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UC-MSCs Group, Control Group
	Comments	The null hypothesis is the following: "There is no association between PRA (class I) status and treatment group at 6 days post first infusion".
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	UC-MSCs Group, Control Group
	Comments	The null hypothesis is the following: "There is no association between PRA (Class II) status and treatment group at 6 days post first infusion".
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Fisher Exact
	Comments

50. Secondary Outcome

Title	Number of Participants Reporting Panel Reactive Antibody (PRA) Positivity at Day 14 Post First Infusion
Description	Number of participants reporting panel reactive antibody (PRA) positivity at Day 14 post first infusion for class I and class II as assessed via serum blood samples. These antibodies can develop following a transplant. Recipients can become sensitized to certain molecules (Human Leukocyte Antigen Class I or Class II), which can affect immune responses to and rejection of potential future transplants.
Time Frame	day 14

Outcome Measure Data

Analysis Population Description
In the UC-MSC group one patient was censored and died before day 6, 6 patients left the hospital before day 6 post first infusion. In the control group 4 patients died, 3 patients left the hospital and one left hospital against medical advice before day 6 post first infusion.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	5	4
PRA Positive	5 41.7%	3 25%
PRA Negative	0 0%	1 8.3%
PRA Positive	4 33.3%	2 16.7%
PRA Negative	1 8.3%	2 16.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UC-MSCs Group, Control Group
	Comments	The null hypothesis is the following: "There is no association between PRA (class I) status and treatment group at 14 days post first infusion".
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.44
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	UC-MSCs Group, Control Group
	Comments	The null hypothesis is the following: "There is no association between PRA (class II) status and treatment group at 14 days post first infusion".
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.5238
	Comments
	Method	Fisher Exact
	Comments

51. Secondary Outcome

Title	Number of Participants With Positive, Negative, or Borderline Serology Testing for SARS-CoV-2 IgM/IgG
Description	Number of participants with positive, negative, or borderline SARS-CoV-2 Immunoglobulin M (IgM)/Immunoglobulin G (IgG) serology from serum blood samples.
Time Frame	day 14 post first infusion

Outcome Measure Data

Analysis Population Description

These analyses were implemented in a protocol version that did not apply to 2 patients of the UC-MSC treatment group and 3 patients of the control group. In the UC-MSC group one patient was censored and died before day 6, 4 patients left the hospital before day 6 post first infusion and in one patient blood was not drawn. In the control group 3 patients died, 3 patients left the hospital and one left hospital against medical advice before day 6 post first infusion.

Arm/Group Title	UC-MSCs Group	Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.	Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
Measure Participants	4	2
Positive	2 16.7%	2 16.7%
Negative	1 8.3%	0 0%
Borderline	1 8.3%	0 0%
Positive	4 33.3%	2 16.7%
Negative	0 0%	0 0%
Borderline	0 0%	0 0%

Adverse Events

	UC-MSCs Group		Control Group
Time Frame	3 months
Adverse Event Reporting Description

Arm/Group Title	UC-MSCs Group		Control Group
Arm/Group Description	Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.: UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.		Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment. Vehicle + Heparin along with best supportive care: Best supportive care treatment per the treating hospital protocol.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/12 (25%)		7/12 (58.3%)
Serious Adverse Events
	UC-MSCs Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/12 (41.7%)		8/12 (66.7%)
Cardiac disorders
Cardiact Arrest-Death due to Difficult Intubation	1/12 (8.3%)	1	0/12 (0%)	0
Atrial Flutter	1/12 (8.3%)	1	0/12 (0%)	0
Cardiac Arrest/Pulseless Electrical Activity Cardiac Arrest/Cardiac Arrest Secondary to Acute Respir	0/12 (0%)	0	3/12 (25%)	3
[DEATH] Cardiac Arrest-Death/Cardiopulmonary Arrest-Death/Asystole -Death	1/12 (8.3%)	1	4/12 (33.3%)	4
Gastrointestinal disorders
GI Bleeding 2ry to Clostridium Difficile Infection	1/12 (8.3%)	1	0/12 (0%)	0
Colon Perforation	1/12 (8.3%)	1	0/12 (0%)	0
General disorders
[DEATH] Multisystem Organ Failure (Death)/Multiple Organ Dysfunction Syndrome-Death	0/12 (0%)	0	2/12 (16.7%)	2
Infections and infestations
Septic Shock-Hospital acquired Pseudomona Aeruginosa bacteremia	0/12 (0%)	0	1/12 (8.3%)	1
Metabolism and nutrition disorders
Hyperkalemia	0/12 (0%)	0	1/12 (8.3%)	1
Severe Metabolic Acidosis	0/12 (0%)	0	1/12 (8.3%)	1
Psychiatric disorders
Psychosis	0/12 (0%)	0	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory Failure 2ry to COVID-Death	1/12 (8.3%)	1	0/12 (0%)	0
Death-Acute Hypoxemic Respiratory Failure Secondary to COVID-19 Pneumonitis	0/12 (0%)	0	1/12 (8.3%)	1
Traumatic Tension Pneumotorax post-CPR	0/12 (0%)	0	1/12 (8.3%)	1
Severe Respiratory Acidosis	0/12 (0%)	0	1/12 (8.3%)	1
Other (Not Including Serious) Adverse Events
	UC-MSCs Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/12 (66.7%)		10/12 (83.3%)
Blood and lymphatic system disorders
Anemia	0/12 (0%)	0	2/12 (16.7%)	2
Leukocytosis/Leukocytosis (Increased WBC)	3/12 (25%)	3	3/12 (25%)	3
Severe Thrombocytopenia	0/12 (0%)	0	1/12 (8.3%)	1
Thrombocytopenia/Heparin-induced Thrombocytopenia	2/12 (16.7%)	2	0/12 (0%)	0
Thrombocytosis	0/12 (0%)	0	1/12 (8.3%)	1
Cardiac disorders
Atrial Fibrillation	0/12 (0%)	0	1/12 (8.3%)	1
Bradycardia	1/12 (8.3%)	1	1/12 (8.3%)	1
Tachycardia	2/12 (16.7%)	2	0/12 (0%)	0
Tachycardia after infusion of Investigational Product	0/12 (0%)	0	1/12 (8.3%)	1
Endocrine disorders
Hyperglycemia	0/12 (0%)	0	2/12 (16.7%)	2
Gastrointestinal disorders
Clostridium Difficile Infection	0/12 (0%)	0	1/12 (8.3%)	1
Mild Gastrointestinal Bleeding	1/12 (8.3%)	1	0/12 (0%)	0
General disorders
Fever	3/12 (25%)	3	2/12 (16.7%)	2
Hepatobiliary disorders
Transaminitis/Transaminitis-Liver Shock	0/12 (0%)	0	2/12 (16.7%)	3
Increased ALT, AST, and Alkaline Phosphatase	0/12 (0%)	0	1/12 (8.3%)	1
Increased Direct Bilirubin	0/12 (0%)	0	1/12 (8.3%)	1
Infections and infestations
Exacerbation of COVID ARDS-Septic Shock	1/12 (8.3%)	1	0/12 (0%)	0
Candida Albicans Fungemia	1/12 (8.3%)	1	0/12 (0%)	0
MRSA Bacteremia	1/12 (8.3%)	1	0/12 (0%)	0
Paenebacillus Pabuli Bacteremia	1/12 (8.3%)	1	0/12 (0%)	0
Positive Blood Culture Streptococcus Mitis and Streptococcus Oralis	1/12 (8.3%)	1	0/12 (0%)	0
Staphylococcus haemolyticus bacteremia and Candida orthopsilosi Fungemia	0/12 (0%)	0	1/12 (8.3%)	1
Staphylococcus Hominis Bacteremia/Staphylococcus Bacteremia	1/12 (8.3%)	1	1/12 (8.3%)	1
Metabolism and nutrition disorders
Hypernatremia	2/12 (16.7%)	2	0/12 (0%)	0
Mild Hyponatremia	1/12 (8.3%)	1	1/12 (8.3%)	1
Hypokalemia	1/12 (8.3%)	1	0/12 (0%)	0
Hyperkalemia	1/12 (8.3%)	1	0/12 (0%)	0
Musculoskeletal and connective tissue disorders
Left Calf Collection	0/12 (0%)	0	1/12 (8.3%)	1
Nervous system disorders
Encephalopathy	1/12 (8.3%)	1	0/12 (0%)	0
Dysconjugated gaze	0/12 (0%)	0	1/12 (8.3%)	1
Renal and urinary disorders
Abnormal Urinalysis	1/12 (8.3%)	1	0/12 (0%)	0
Candiduria	0/12 (0%)	0	1/12 (8.3%)	1
Urinary Tract Infection	1/12 (8.3%)	1	1/12 (8.3%)	1
Acute Kidney Injury/Oliguric Acute Kidney Injury/ Anuric Acute Kidney Injury/Acute Kidney Injury (AK	2/12 (16.7%)	2	5/12 (41.7%)	5
Respiratory, thoracic and mediastinal disorders
Pneumoperitoneum	0/12 (0%)	0	1/12 (8.3%)	1
Aspiration Pneumonitis, suspected	1/12 (8.3%)	1	0/12 (0%)	0
Bradypnea	0/12 (0%)	0	1/12 (8.3%)	1
Enterococcus Faecalis, Klebsiella Pneumoniae, Candida Auris/Duobushaemulonis in bronchial aspirate	1/12 (8.3%)	1	0/12 (0%)	0
Enterococcus Pneumonia	1/12 (8.3%)	1	0/12 (0%)	0
MRSA Hospital Acquired Pneumonia	2/12 (16.7%)	2	0/12 (0%)	0
Pneumomediastinum	1/12 (8.3%)	1	0/12 (0%)	0
Respiratory Failure - Intubation/Hypoxemic respiratory failure requiring intubation and mechanical v	1/12 (8.3%)	1	1/12 (8.3%)	1
Subcutaneous Emphysema	1/12 (8.3%)	1	0/12 (0%)	0
Ventilator Acquired Pneumonia (VAP) with Pseudomona aureginosa	0/12 (0%)	0	1/12 (8.3%)	1
Worsening of Hypoxemia/Deterioration of Hypoxia	4/12 (33.3%)	4	0/12 (0%)	0
Vascular disorders
Bilateral Common Femoral Vein DVT	0/12 (0%)	0	1/12 (8.3%)	1

Limitations/Caveats

The inferences we make from the efficacy results observed in this phase 1/2a trial in 24 subjects, including the outcome of survival, are still subject to limitations of sample size and potential bias because of factors we were not yet aware of.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title	Camillo Ricordi
Organization	University of Miami
Phone	305-243-6913
Email	ricordi@miami.edu

Responsible Party:

Camillo Ricordi, Professor of Surgery and Chief, Division of Cellular Transplantation, University of Miami

ClinicalTrials.gov Identifier:

NCT04355728

Other Study ID Numbers:

20200671
20200370

First Posted:

Apr 21, 2020

Last Update Posted:

Dec 6, 2021

Last Verified:

Dec 1, 2021