A groundbreaking new therapeutic approach was developed and tested to improve outcome in patients suffering from novel coronavirus (COVID-19) pneumonia. The new technique involves intravenous transplantation of mesenchymal stem cells (MSCs) into the patients. It was successfully tested in 7 COVID-19 patients, in Beijing YouAn Hospital, Capital Medical University, China. The results are published in the scientific journal Aging and Disease, entitled "Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia".
The study was conducted by a team led by Dr. Zhao, with Shanghai University and Chinese Academy of Medical Sciences & Peking Union Medical College, China.
The novel coronavirus disease 2019 (COVID-19) has grown to become a global public health emergency. 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 severe cases. This study provides a promising pathway for developing such a treatment.
The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of all the seven tested patients without observed adverse effects, contrary to 3 controls. The pulmonary function and symptoms of these seven patients were significantly improved after MSC transplantation. Among them, one severe and two common patients recovered and were discharged in 10 days after the treatment.
Before the MSC transplantation, all the patients had pneumonia with symptoms of high fever (38.5℃ ± 0.5℃), weakness, shortness of breath, and low oxygen saturation. However, 2~4 days after transplantation, all the symptoms disappeared in all the patients, the oxygen saturations rose to ≥ 95% at rest. In addition, no acute infusion-related or allergic reactions were observed.
The improvement was particularly dramatic for an elderly (65 y.o.) male patient in severe critical condition. All of the primary and secondary outcomes improved: the inflammation status quickly alleviated, the oxygen saturation, without supplementary oxygen, was increased, functional biochemical indicators were restored to normal reference values in 2~4 days after treatment. The respiratory rate was decreased to the normal range on the 4th day after the stem cell transplantation. Both fever and shortness of breath disappeared on the 4th day after the stem cell transplantation. Chest CT imaging showed that the pneumonia infiltration was largely reduced. The virus detecting test for HCoV-19 nucleic acid turned from positive to negative, as well as for 3 other treated patients. In the severe patients, the vitally important immune cells, such the regulatory T cells and dendritic cells (DC) increased after the cell therapy, especially for the critically severe patient, showing a restoration of the immune function.
The presented evidence suggests that the therapeutic effects are based on the immunomodulatory capacity of mesenchymal stem cells (restoring the balance of the immune system). The coronavirus infection can stimulate a terrible cytokine storm in the lung, disrupting the balance of cytokines (signaling molecules of the immune system) such as IL-2, IL-6, IL-7, GSCF, IP10, MCP1, MIP1A and TNFα cytokines, followed by the edema, dysfunction of the air exchange, acute respiratory distress syndrome, acute cardiac injury and the secondary infection, which may lead to death. MSCs could inhibit the over-activation of the immune system and promote endogenous repair by improving the microenvironment, thus they could represent a safe and effective treatment for patients with COVID-19 pneumonia, especially for the patients in critically severe conditions.
Notably, the coronavirus-infected pneumonia is more likely to affect older individuals, especially older males, with comorbidities, resulting in their severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In other words, aging appears to be the main risk factor for bad outcomes. However, the cure essentially depends on the patient's own immune system. When the overactivated immune system kills the virus, it produces a large number of inflammatory factors, leading to the severe cytokine storms. This suggests that the main reason for the organs damage may be the virus-induced cytokine storm. Older subjects may be much easier to be affected due to immunosenescence. The study showed remarkable recovery of the elderly patients thanks to restoring their immune function. Thus, the study may have a broader significance, even beyond the treatment of the severe coronavirus disease. This study exemplifies that the general therapeutic improvement of the immune system in the elderly can improve outcome and survival, which may have more general relevance for other aging-related communicable diseases. Thus, this study may inspire and pave the way for further promising directions to investigate the connection between aging and disease, and to treat both communicable and non-communicable aging-related diseases.
For more details, please contact the study leaders and corresponding authors:
Dr. Robert Chunhua Zhao, School of Life Sciences, Shanghai University, Shanghai, China. International Society on Aging and Disease (ISOAD). UNESCO Committee on Anti-aging and Disease Prevention. Email: firstname.lastname@example.org
Dr. Kunlin Jin, University of North Texas Health Science Center, Fort Worth, TX 76107, USA. International Society on Aging and Disease (ISOAD). UNESCO Committee on Anti-aging and Disease Prevention. Email: kunlin.Jin@unthsc.edu
Contact also: Dr. Ilia Stambler, Outreach coordinator of the International Society on Aging and Disease (ISOAD), and UNESCO Committee on Anti-aging and Disease Prevention. Email: email@example.com