A 8-Week Trial of Mesenchymal Stem Cells Therapy in Patients With COVID-19 Pneumonia
Phase: NA
Conditions: Coronavirus Disease 2019 (COVID-19) Pneumonia
Sponsor: Kanuni Sultan Suleyman Training and Research Hospital

Mesenchymal stem cells Therapy in Patients with COVID-19 Pneumonia 
 
Date: 04 May 2020-30 July 2020 
 
Attached is a copy of trial by Ayca Sultan Sahin titled ‘Mesenchymal stem cells Therapy in 
Patients with COVID-19 Pneumonia’ which is being submitted.  
This trial is original, it is not being considered for publication elsewhere. Our trial is original 
because the application of MCSs in COVID-19 pneumonia patients are not common. 
Correspondence regarding this trial is Ayca Sultan Sahin, at the address indicated in the forms. 
Looking forward to hearing from you soon. Many thanks in advance for your consideration and 
cooperation. 
 
Purpose of our study: 
Due to the cytokine storm that develops as a result of COVID-19 infection, some patients are 
hospitalized to intensive care unit for pneumonia, ARDS and multiple organ failure. Mortality 
is higher in treatment-resistant cases. 
1) 
Providing immune modulation by Stem Cell Transplantation and reducing the damage 
caused by cytokine storm to tissues and organs, 
2) 
Correcting immunosuppression and fight against COVID-19 virus by editing B and T 
cells, 
3) 
It is to accelerate healing in organ damage by increasing growth factors through 
mesenchymal stem cells. 
Primary outcome: Weaning of patients, from mechanical ventilation 
Secondery outcome: Improvement of clinical symptoms, reduction of cytokine storm 
Clinical outcome assessment 
The patients were observed after MSC infusion, and clinical symptoms, laboratory tests, and 
radiological results were recorded and confirmed by experienced physicians. The primary 
clinical outcomes included the incidence of progression from severe to critical illness and the 
time to a clinical improvement of two points on a seven-category ordinal scale that has been 
used widely in clinical symptom assessment or discharge from the hospital. The secondary 
clinical outcomes included patient status at days 7 and 14 assessed with a seven-category 
ordinal scale, hospital stay, changes in oxygenation index, hematological inflammatory 
factors, and imaging. 
 

Methods 
Study design and participants  
This study was a single-center open-label, randomized trial conducted at an Education and 
Training Hospital, Istanbul from May to July, 2020, and it was performed according to the 
Declaration of Helsinki and approved by the Ethics Committee and health ministry 
(No.KAEK/2020.05.20). Written informed consent was obtained from all patients or their 
representatives when data were collected prospectively. 
Age, gender, mortality status, APACHE II score, number of days in bed, procalcitonin and 
CRP values, leukocyte values, concomitant diseases, CD4, CD8, IL-2, IL-6, TNF-alpha-beta 
levels will be recorded. These tests are studied in the conditions of our hospital. 
Clinical results, changes in inflammatory and immune function levels, and side effects will be 
evaluated. The patient's lung function and symptoms will be recorded in the days after MSC 
transplantation. After treatment, lymphocyte, C-reactive protein, TNF-a level, IL-6 levels will 
be recorded. 
Patients were divided into 3 groups: (Figure 1) 
1.group: Intubated without comorbidity (n:7) 
2.group: Intubated with comorbidity (n:7) 
3.group: No intubated (n:7) 
Dosage of MSCs:  
1. 
1 million cell/kg iv--------------------------------------------------day 0 
2. 
1 million cell/kg iv -------------------------------------------------day 2 
3. 
1 million cell/kg iv -------------------------------------------------day 4 
Inclusion criteria included the following: 
• aged 18-80 male or female 
• laboratory approve of RT-PCR with 2019-nCoV infection 
• pneumonia assessed by chest radiography or computed tomography 
• In accordance with any of the following:  
1) Respiratory rate ≥ 30 times / min  
2) oxygen saturation ≤ 93% 
3) PaO2/FiO2) ≤ 300MMHG 
4) pulmonary imaging of focus within 24-48 hours > 50% progression 
• patients who remain unresponsive to medications administered according to Ministry of 
health guidelines 

• Patients who receiving invasive or non-invasive mechanical ventilation therapy in intensive 
care 
 
Exclusion criteria included the following: 
• 
Pregnancy 
• 
Any kind of cancer, severe liver disease 
• 
Failure to provide informed consent or comply with test requirements 
• 
Known allergy or hypersensitivity to MSCs 
 
Statistical Analyses 
CD values 
Stem cell therapy received patients who were divided into 3 groups have the following 
descriptive characteristics in terms of CD values (Table 1: mean±standard deviation) 
according to dosage of MSCs. Four different time periods were handled as “Time 0” (before 
MSCs infusion,) and as “Time 1”, “Time 2” and “Time 3” (after 1st infusion, after 2nd 
infusion, after 3th infusion, respectively).  Linear mixed effects model was used whether both 
the groups and time affected blood values differently. Given 21 stem cell therapy received 
patients, the linear mixed‐effects model can be described as follows: 
 
 
 
 
 
 
 
 
 
 
 
where  
 is the vector of blood values for patient  and 
  is the design matrix.    is a 
vector of fixed effects (group and time) that are common to all patients and   is a vector of 
random effects (subject-specific). The model is a linear combination of fixed and random 
effects where random effects are assumed to have normal distribution  
 The 
residual vector  
 Models were estimated with nlme package in R-Studio 
 
Clinical Behavior 
Clinical behaviours of stem cell therapy received patients were divided into 3 groups and the 
blood values were recorded for different six time periods such as “Time 0” (before MSCs 
infusion) “Time 1” (after 1st infusion), “Time 2” (after 2nd infusion), “Time 3” (after 3th 
infusion), “Time 4” (extubation time) and “Time 5” (discharge time). Table 2 shows the 
descriptive characteristics (mean±standard deviation) of blood values according to dosage of 
MSCs. Linear mixed effects model was used whether both the groups and time affected blood 
values differently. 
 

Figure 1. Flow diagram of the study     
 
  
 
Enrollment 
Analysis 
42 patients assessed for eligibility 
 21: Not meeting acceptance 
criteria 
Providing immune modulation by Stem Cell Transplantation and reducing the 
damage caused by cytokine storm to tissues and organs. 
 
It is to accelerate healing in organ damage by increasing growth factors through 
mesenchymal stem cells. 
Primary Outcome 
Secondary Outcome 
                     21 patients  
1.group: Intubated with comorbidity (n:7) 
2.group: Intubated without comorbidity (n:7) 
3.group: No intubated (n:7)