Bone Marrow-Derived Mesenchymal Stem Cell Treatment for Severe Patients With Coronavirus Disease 2019 (COVID-19)
Bone Marrow-Derived Mesenchymal Stem Cell Treatment for Severe Patients With Coronavirus Disease 2019 (COVID-19)
Coronavirus Disease 2019 (COVID-19) is spreading worldwide and has become a public health
 emergency of major international concern. Currently, no specific drugs or vaccines are
 available. For severe cases, it was found that aberrant pathogenic T cells and inflammatory
 monocytes are rapidly activated and then producing a large number of cytokines and inducing
 an inflammatory storm.Mesenchymal stem cells (MSCs) have been shown to possess a
 comprehensive powerful immunomodulatory function. This study aims to investigate the safety
 and efficacy of intravenous infusion of mesenchymal stem cells in severe patients with
 COVID-19.
COVID-19 has become a urgent and serious public health event that threatens human life and
 health globally. No specific pharmacological treatments are available to date for
 COVID-19.Patients contracting the severe form of the disease constitute approximately 15% of
 the cases which is characterized by extensive acute inflammation. In these severe cases,
 there will be rapid respiratory system failure.

 MSCs have been employed extensively in cell therapy, which includes a plethora of preclinical
 research investigations as well as a significant number of clinical trials. Safety and
 efficacy have been shown in many clinical trials. Previous studies have shown that MSCs could
 significantly reduce inflammatory cell infiltration in lung tissue, reduce inflammation in
 lung tissue, and significantly improve lung The structure and function of tissues protect
 lung tissue from damage.The mechanisms underlying the improvements after MSC infusion in
 COVID-19 patients also appeared to be the robust antiinflammatory activity of MSCs. Recent
 studies also showed that intravenous MSC infusion could reduce the overactivation of the
 immune system and support repair by modulating the lung microenvironment after SARS-CoV-2
 infection. MSC therapy inhibiting the overactivation of the immune system and promoting
 endogenous repair by improving the lung microenvironment after the SARS-CoV-2 infection.

 The purpose of this study is to investigate the safety and efficacy of intravenous infusion
 of mesenchymal stem cells in severe patients With COVID-19.The respiratory function,
 pulmonary inflammation, clinical symptoms, pulmonary imaging, side effects, immunological
 characteristics will be evaluated.
Inclusion Criteria:

 1. Willing and able to provide written informed consent prior to performing study
 procedures

 2. Age ≥18 years, and ≤75 years;

 A confirmed case of Covid-19. The criteria are as follows:

 Clinically diagnosed or suspected cases with one of the following etiological
 evidence: 1) SARS-CoV-2 nucleic acid is positive in respiratory or blood samples
 detected by RT-PCR; 2) virus sequence detected in respiratory or blood samples shares
 high homology with the known sequence of SARS-CoV-2.

 3. Clinical classification is severe case: Meet any of the following:

 1) Increased respiratory rate (≥30 beats / min), difficulty breathing, cyanosis of the
 lips; 2) Peripheral capillary oxygen saturation (SpO2) ≤93% at rest ; 3)Partial pressure of
 arterial oxygen (PaO2) / Fraction of inspired oxygen (FiO2) ≤300 mmHg (1mmHg = 0.133kPa).

 Exclusion Criteria:

 1. Other types of viral pneumonia, or bacterial pneumonia.

 2. The clinical classification is mild, moderate or critical;

 3. Patients with malignant blood or solid tumor.

 4. Pregnant or lactating women;

 5. There are other situations or diseases that the investigator think are not suitable to
 participate in this clinical study or may be increased risk of the subject.

 6. Patients with serious social and mental disability, inability/restriction of legal
 capacity;

 7. Refusal to sign informed consent;

 8. Patients with severe liver disease (eg Child Pugh score ≥ C, AST> 5 times upper limit
 of normal );

 9. Patients with severe renal insufficiency (estimated glomerular filtration rate ≤30mL /
 min / 1.73m2) or receiving continuous renal replacement therapy, hemodialysis,
 peritoneal dialysis.