By Ilia Stambler, PhD
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. A new study offers a promising pathway for developing such a treatment.
The new approach 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”.
https://doi.org/10.14336/AD.2020.0228
The study was conducted by a team led by Dr. Robert Chunhua Zhao, with Shanghai University and Chinese Academy of Medical Sciences & Peking Union Medical College, China.
Moreover the study was reviewed by a scientific committee of the International Society on Aging and Disease (ISOAD) and the recently established UNESCO-affiliated committee on Anti-Aging and Disease Prevention http://www.aginganddisease.org/EN/10.14336/AD.2019.1230
Based on the 14 days observation, 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. The improvement was particularly dramatic for an elderly (65 y.o.) male patient in severe critical condition. All of his primary and secondary outcomes improved: the inflammation status, the oxygen saturation, and the functional biochemical indicators returned to normal reference values in 2~4 days after the treatment.
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. The bone-marrow derived 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. A larger validation study is required and is already underway, yet the initial results are encouraging.
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.
The Romanian journalist Laura Ștefănuț spoke with Dr. Ilia Stambler about the broader implications of this research. Ilia Stambler is a co-author in this study who was involved in the study review, interpretation and discussion. He serves as the Outreach Coordinator of the International Society on Aging and Disease (ISOAD) and Director of Research and Development at Shmuel Harofe Geriatric Medical Center in Israel.
Q: How does it feel to be part of the team which discovered a groundbreaking treatment for what is currently considered one of the biggest global challenges?
A: I feel very honored to be included in this extended international team. I hope this team continues its work that will also involve additional collaborations.
Q: As a researcher, what did you find most interesting about this novel coronavirus? What seems most threatening about this new virus?
A: The spreading ability of this virus is relatively high and it has the capacity to affect the entire global population. This is what makes this virus a particularly strong concern for global public health. The social effects of this epidemic are also of great importance. In a sense, this virus is testing the strength of our public health systems. Will the immunity of our public healthcare be strong enough to contain it? I hope it is.
Q: Did the discovery of this groundbreaking new therapeutic approach make you more optimistic (when it comes to containing and limiting the damage of Covid-19)? In which sense (where was your optimism before the discovery)?
A: I was optimistic before, as I believe that, same as for many infectious diseases in the past, also for this disease, effective therapeutic and preventive measures will be found and used. This work further increased my optimism. Of course, this is an initial study, and this is only one of the potential means in the therapeutic, preventive and hygienic arsenal. More research and confirmation will be needed. Yet, even at this stage, the clear positive result of this study shows that it is indeed possible to improve the outcomes for COVID-19 patients even in severe conditions. Moreover, it gives more hope that effective treatments can be sought and found also for other aging-related infectious diseases and conditions.
Q: Is there an explanation regarding the reasons why Covid-19 seems to “pardon” children and affects the most elder individuals, especially men?
A: There is yet no clear or fully agreed explanation. But a plausible cause may be due to the so called “immuno-senescence” phenomenon, or the inability of the aging immune system to cope with new threats and restore the immune balance following the infection. In men the immuno-senescence effects are often more strongly present than in women. Thus, aging appears to be the main risk factor for this disease and if we really wish to defeat this epidemic, we need to address this main risk factor, in other words, we need to therapeutically intervene and ameliorate the degenerative aging process. The proposed mesenchymal stem cell therapy shows the so-called “immuno-modulation” effects or the ability to generally improve the immune system, help restore the immune balance after disturbances, especially for the elderly. And this can be the more general explanation for its effects against the aging-related COVID-19 pneumonia, as well as potentially other aging-related diseases.
Q: How did you manage to find so fast a treatment that is responding so well?
A: The mesenchymal stem cell treatment has been researched and developed by Dr. Zhao and his team for many years, and indicated positive effects for multiple health conditions. It is exactly because of the common and critical role of the immune system impairment in all these conditions, that the treatment developed by Dr. Zhao’s team was already in place and could be immediately used also for this condition dependent on the immune function. Moreover, the success of this therapy against COVID-19 can further boost the research and therapy of other immunity-dependent health conditions and diseases, especially aging-related diseases, due to the common mechanisms of action.
Q: How may this discovery change the game?
A: Unlike other public health measures, like quarantine and hygiene, that can be very quickly applied, the research, development, regulatory approval and application of new therapies is a much slower process. So we should first of all apply the public health measures to contain the epidemic. But the hope is that this therapy will undergo further research and validation as soon as possible, and in case of validated efficacy and safety, will be used in as many patients who need it as possible, as soon as possible. That is exactly why we need to accelerate the research, development and application of promising new therapies. When the new therapy enters wide clinical practice, there are grounds to believe it can improve the health and even save the lives of many patients, not only suffering from COVID-19, but also other conditions.
Q: Which was the response/reaction of authorities after you published the results of your research?
A: The outreach to the authorities in several countries has only started. Moreover, the study is only initial and it is too early to make policy recommendations. A larger validation study is required. Yet, if there is even a slight possibility this could become a life-saving therapy for COVID-19 patients and others, this opportunity should not be missed by the decision makers.
Q: Some treatments are more expensive than others. Will the treatment you discovered be accessible to people, or the cost for producing it will limit its accessibility?
A: The cells for this treatment can be mass produced and can be rather affordable. Of course, the actual price will depend both on the scale of production and pricing policies. And this is already a question that goes beyond pure technology, but becomes a question about the social means to make new therapies available to all. This should also be a crucial part of the public discussion about the social need to promote the rapid research and development as well as broad application of new therapies that are proven to be safe and effective.
Q: Which are the best measures a country can take to limit the spread and the consequences of the novel coronavirus?
The usual quarantine and public hygiene measures are the most feasible and effective: minimization of large gatherings, minimization of travel, cleanliness. We should hope and work for new effective therapies to arrive as soon as possible. But so far public health measures are the most effective and feasible.
We hereby call on WHO and country leaders for maximum openness of medical data from patients with the coronavirus SARS-CoV-2, to enhance medical research and the development of new therapies and treatment regimens against this world-threatening disease. Especially, we demand more research and development to therapeutically address aging as the main contributing factor for disability and deaths in this disease, for example to improve the immunity in older people. Data openness is necessary to facilitate such research and achieve safe, effective and accessible therapies, as soon as possible, to combat COVID-19 and other diseases that have aging as the main risk factor. Support this initiative! Sign the petition!