The COVID-19 pneumonia has grown to be a global public health emergency since patients were first detected in Wuhan, China, in December 2019, which spread quickly to worldwide and presented a serious threat to public health. It is mainly characterized by fever, dry cough, shortness of breath and breathing difficulties. Some patients may develop into rapid and deadly respiratory system injury with overwhelming inflammation in the lung. Currently, no specific drugs or vaccines are available to cure the patients with COVID-19 pneumonia. Hence, there is a large unmet need for a safe and effective treatment for COVID-19 pneumonia patients, especially the critically ill cases. The significant clinical outcome and well tolerance was observed by the adoptive transfer of allogenic MSCs. We proposed that the adoptive transfer therapy of MSCs might be an ideal choice to be used. We expect to provide new options for the treatment of critically ill COVID-19 pneumonia patients and contribute to improving the quality of life of critically ill patients.
Since December 2019, novel coronavirus disease 2019 (COVID-19) in Wuhan has been fierce and
spread rapidly. As of 24:00 on March 4, 2020, China has reported a total of 80567 confirmed
cases, 5952 existing critically ill cases, and 3016 dead cases. The COVID-19 pneumonia has
grown to be a global public health emergency since patients were first detected in Wuhan,
China, in December 2019, which spread quickly to 26 countries worldwide and presented a
serious threat to public health. It is mainly characterized by fever, dry cough, shortness of
breath and breathing difficulties. Some patients may develop into rapid and deadly
respiratory system injury with overwhelming inflammation in the lung. Currently, no specific
drugs or vaccines are available to cure the patients with COVID-19 infection. Hence, there is
a large unmet need for a safe and effective treatment for COVID-19 infected patients,
especially the critically ill cases.
Recently, some clinical researches about the COVID-19 published in The Lancet and The New
England Journal of Medicine suggested that massive inflammatory cell infiltration and
inflammatory cytokines secretion were found in patients' lungs, alveolar epithelial cells and
capillary endothelial cells were damaged, causing acute lung injury. Several reports
demonstrated that the first step of the HCoV-19 pathogenesis is that the virus specifically
recognizes the angiotensin I converting enzyme 2 receptor (ACE2) by its spike Protein. This
receptor is abundant in lung and small intestinal tissues, but is also highly expressed in
vascular endothelial cells and smooth muscle cells in almost all organs, including the
nervous system and skeletal muscle. The main organ injured by the HCoV-19 is the lung. In
fact, HCoV-19 can also involve the nervous system, digestive system, urinary system, blood
system and other systems. Therefore, when the initial symptom is discomfort of other systems
in the early stage, it is often easy to be misdiagnosed and delay treatment. Moreover, the
HCoV-19 is a noncellular form consisting of RNA and protein, which cannot be copied
independently. It needs to bind to cell surface receptors to enter the cell to complete the
replication, and then be released again. Therefore, once the HCoV-19 enters the blood
circulation, it can easily spread to all systems throughout the body, which may be the
pathological mechanism that the HCoV-19 directly or indirectly causes neurological symptoms.
It seems that the key to cure the COVID-19 pneumonia is to inhibit the inflammatory response,
resulting to reduce the damage of alveolar epithelial cells and endothelial cells and repair
the function of the lung. MSCs, owing to their powerful immunomodulatory ability, may have
beneficial effects on preventing or attenuating the cytokine storm.
Mesenchymal stem cells (MSCs) are widely used in basic research and clinical application.
They are proved to migrate to damaged tissues, exert antiinflammatory and immunoregulatory
functions, promote the regeneration of damaged tissues and inhibit tissue fibrosis. MSCs play
a positive role mainly in two ways, namely immunomodulatory effects and differentiation
abilities. MSCs can secrete many types of cytokines by paracrine secretion or make direct
interactions with immune cells, leading to immunomodulation. Studies have shown that MSCs can
significantly reduce acute lung injury in mice caused by H9N2 and H5N1 viruses by reducing
the levels of proinflammatory cytokines and the recruitment of inflammatory cells into the
lungs. Compared with MSCs from other sources, human umbilical cord-derived MSCs (UC-MSCs)
have been widely applied to various diseases due to their convenient collection, no ethical
controversy, low immunogenicity, and rapid proliferation rate.
Here we conducted an MSC transplantation pilot study to explore their therapeutic potential
for COVID-19 pneumonia patients. To explore the effective treatment of COVID-19 pneumonia for
the current prevention and control of novel coronavirus pneumonia to find a key and effective
clinical treatment means, to fight against the epidemic.
Biological: UC-MSCs
1*10E6 UC-MSCs /kg body weight suspended in 100mL saline
Other: Placebo
100mL saline intravenously
Inclusion Criteria:
1. Male or female, 18 years old ≤ age ≤ 75years old;
2. CT image is characteristic of 2019 novel coronavirus pneumonia;
3. Laboratory confirmation of 2019-nCoV infection by reverse transcription polymerase
chain reaction (RT-PCR);
4. In compliance with the 2019-nCoV pneumonia diagnosis standard (according to the novel
coronavirus infection pneumonia diagnosis and treatment program (Trial Implementation
Version 6) issued by the National Health and Medical Commission, and WHO 2019 new
coronavirus guidelines standards): (A) increased breathing rate (≥30 beats / min),
difficulty breathing, cyanosis of the lips; (B) in resting state, means oxygen
saturation ≤93%; (C) partial pressure of arterial oxygen (PaO2) / Fraction of inspired
oxygen (FiO2) ≤300 mmHg (1mmHg = 0.133kPa);
5. Participant or the authorized agent signed the informed consent form.
6. Agree to collect clinical samples.
Exclusion Criteria:
1. Malignant disease in the past five years;
2. Participant with no hope of survival were clinically predicted and only received
hospice care, or those who were in a deep coma and did not respond to supportive
treatment measures within three hours of admission.
3. Participant who are participating in other clinical trials or who have participated in
other clinical trials within 3 months.
4. Cases of severe shock and respiratory failure.
Puren Hospital Affiliated to Wuhan University of Science and Technology
Wuhan, Hubei, China
Investigator: Yan Liu, MD
Contact: +8613387517458
447822853@qq.com
Yan Liu, MD
+8613387517458
447822853@qq.com
Yue Zhu
+8617786289703
978925651@qq.com