When to Apply to Which Patient in MSC?

Study Overview
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Brief Summary
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Mesenchymal stem cell (MSC) therapy is among the promising treatments for acute respiratory distress syndrome (ARDS). Our study aimed to investigate the clinical efficacy of MSC treatment in COVID-19 patients, to determine when this treatment can be applied to which patient, and to evaluate its contribution to prognosis.

Detailed Description
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The study was conducted retrospectively in patients diagnosis of COVID-19 in the intensive care units. Patients with severe ARDS [partial pressure of arterial blood oxygen and inhaled oxygen fraction (PaO2: FiO2) ratio of 100 or less] were included in the study. Demographic data of the patients (gender, age), comorbidities (hypertension, coronary heart disease, diabetes, cerebrovascular diseases, hepatitis B infection, cancer, chronic kidney disease, and immunodeficiency), Charlson comorbidity index (CMI), date of diagnosis, date of admission to the hospital, date of admission to the ICU, Acute Physiology And Chronic Health Evaluation (APACHE) II score, presence of high flow nasal oxygen (HFNO) or mechanical ventilator (MV) support, laboratory findings (blood cell count, blood biochemistry, hepatorenal function, coagulation function, D-dimer, C-reactive protein (CRP), procalcitonin, ferritin, arterial blood gas analysis) before (day 0) and after MSC application, on 3rd and 7th days, partial oxygen/fractionated oxygen (Pa/Fi) ratio, discharge or death information, and attributed causes of death were recorded on the study form. Pa/Fi ratio was calculated with the formula (oxygen dissolved in arterial blood gas / oxygen liter given to the patient).

Official Title
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Effectiveness of Mesenchymal Stem Cell in Patients With COVID-19 Associated SARS-CoV-2, Retrospective Clinical Study: When to Apply to Which Patient?

Conditions
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COVID-19 Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: Mesenchymal Stem Cell Antigen-1, Human


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who were followed up and treated after being admitted to the Intensive Care Unit after March 2020 Patients with COVID PCR + Typical or suspected cases of Thorax BT COVID Cases over the age of 18. Exclusion Criteria: Those with a contraindicated condition (cancer disease, allergy) for MSC application Those who are endotracheal intubated during the application and are connected to a respirator Those who died in the first 24 hours after the application Cases that are not positive or suspicious for COVID. Cases under the age of 18. Cases where patient data could not be reached.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| stem cell application; Group I disease 0-7. days,<br>In mesenchymal stem cell application, according to the diagnosis of COVID 19 and the day of stem cell application; Group I disease 0-7. days, | Drug: Mesenchymal Stem Cell Antigen-1, Human<br>* Human umbilical cord-derived MSCs were used in the study. MSCs were prepared/obtained/produced/provided by Atigen-Cell Technology Center, Trabzon, Turkey. MSC for patients was calculated as a single dose, 1x106 cells per kilogram. MSC was infused in 100 ml of normal saline at 2 ml/min over 40 min, as described in previous studies<br>* Other names: Human umblical cord deriveted Mesenchymal Stem Cell;|
| stem cell application; Group II; 8-14 days of the disease. days<br>In mesenchymal stem cell application, according to the diagnosis of COVID 19 and the day of stem cell application; Group II; 8-14 days of the disease. days | Drug: Mesenchymal Stem Cell Antigen-1, Human<br>* Human umbilical cord-derived MSCs were used in the study. MSCs were prepared/obtained/produced/provided by Atigen-Cell Technology Center, Trabzon, Turkey. MSC for patients was calculated as a single dose, 1x106 cells per kilogram. MSC was infused in 100 ml of normal saline at 2 ml/min over 40 min, as described in previous studies<br>* Other names: Human umblical cord deriveted Mesenchymal Stem Cell;|
| stem cell application; Group III; those applied on the 15th day and after.<br>In mesenchymal stem cell application, according to the diagnosis of COVID 19 and the day of stem cell application; Group III; It will be divided into 3 groups as those applied on the 15th day and after. | Drug: Mesenchymal Stem Cell Antigen-1, Human<br>* Human umbilical cord-derived MSCs were used in the study. MSCs were prepared/obtained/produced/provided by Atigen-Cell Technology Center, Trabzon, Turkey. MSC for patients was calculated as a single dose, 1x106 cells per kilogram. MSC was infused in 100 ml of normal saline at 2 ml/min over 40 min, as described in previous studies<br>* Other names: Human umblical cord deriveted Mesenchymal Stem Cell;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in acute phase reactants (C-reactive protein (CRP) after MSC administration in group I, II, III | It was aimed to observe the changes in C-reactive protein (CRP), after MSC administration at different times (groups 1,2,3). | MSC treatment Group I disease 0-7. days, Group II; 8-14 days of the disease. days, Group III; Those applied on the 15th day and after | 
| Change in acute phase reactants (procalcitonin) after MSC administration in group I, II, III | It was aimed to observe the changes in procalcitonin after MSC administration at different times (groups 1,2,3). | MSC treatment Group I disease 0-7. days, Group II; 8-14 days of the disease. days, Group III; Those applied on the 15th day and after | 
| Change in acute phase reactants ( white blood cell count) after MSC administration in group I, II, III | It was aimed to observe the changes in white blood cell count after MSC administration at different times (groups 1,2,3). | MSC treatment Group I disease 0-7. days, Group II; 8-14 days of the disease. days, Group III; Those applied on the 15th day and after | 
| Changes in respiratory support after MSC administration in Groups I, II, III | It was aimed to observe the changes in respiratory support (such as high-flow nasal oxygen, mask with reservoir, and mechanical ventilation) after MSC administration at different times (groups 1,2,3). | MSC treatment Group I disease 0-7. days, Group II; 8-14 days of the disease. days, Group III; Those applied on the 15th day and after | 
| Changes in arterial blood gas analysis (partial oxygen/fractionated oxygen (Pa/Fi) ratio) after MSC administration in Groups I, II, III | It was aimed to observe the changes in arterial blood gas analysis after MSC administration in Groups I, II, III. | MSC treatment before (day 0) and after MSC application, on 3rd and 7th days, | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on mortality after MSC administration in Groups I, II, III | The effect of MSC application at different times on mortality will be evaluated. | 7, 14 and 28 days after MSC application | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, SARS-CoV-2, Mesenchymal Stem Cell, Intensive Care Units