Currently definitive treatment against civid is unavailable while patients are being offered palliative treatment to manage symptoms. Many known therapeutic agents like antivirals (Remdesivir or Hydroxychloroquine) or antiparasitic (Ivermectin) are being evaluated for their efficacy against the disease, although without any comprehensive success. Similarly, the exhaustive work is going on to develop the vaccine against the COVID-19 but that too requires lot more efforts and time. There is lot of buzz about the safety and efficacy of stem cell therapy in COVID-19 patients. Even some have claimed its efficacy far closer to the definitive treatment. The question is whether it really is the treatment of choice is being discussed here.

Stem cells are of various types including the embryonic cells (embryonic stem cells) and those harvested form the adult body tissues (like mesenchymal stem cells). Embryonic stem cells carry good differentiation potential as compared to the adult mesenchymal stem cells (MSCs). Due to the ethical and the teratogenic (tumour forming potential) issues MSCs are being favoured over embryonic stem cells (ESCs). MSCs additionally offer immuno-modulatory and / anti-inflammatory effects and can be harvested from numerous tissue sources including the foetal membranes. As MSCs are immune-compromised (weak potential to elicit immune response), there allogeneic (from other sources) utilization as ready-to-use source becomes possible. MSCs safety and efficacy in various non-infectious immune mediated diseases like Graft-vs-Host disease (GVHD) and Systemic Lupus Erythromatosis (SLE), among others has already been established. MSCs immune-modulation may be achieved either through the direct cell-to-cell contact or through their secretome being enhanced by the inflammatory mediators. Additionally, compared to the drugs that block inflammatory response (IL-6) like tocilizumab MSCs may prove superior by promoting healing of the damaged tissues through their tissue specific differentiation and recruitment of other pro-healing cells.

COVID-19 affects the elderly much more than the young ones and as much as 8 out of 10 patients above 65 years are hard hit. This is due to their weak immune response against the disease as compared to the young ones. In case of some young ones that gets badly affected, harmless genetic or environmental factors might make the immune response overdrive. The inflammatory cells secrete excessive quantity of cytokines without an ability to switch off and form a chain reaction leading to the cytokine storm. This unchecked inflammation and its mediators flood lungs and give rise to acute respiratory distress syndrome (ARDS). MSCs due to the characteristic immune-modulatory features may balance the immune response and prevent overdrive immune response in young ones while in case of elderly patients lack of the sufficient immune response may be compensated. It is worth mentioning here that MSCs directly may not affect the virus but due to their characteristic properties adverse reactions due to viral infection may be prevented.

MSCs are being categorized as Advanced Therapy Medicinal Products (ATMPs) by European Medicines Agency (EMA), meaning possible adverse reaction can arise with their use. Initial clinical trials conducted in China on COVID-19 patients have confirmed their safety and efficacy. Food and Drug Administration (FDA) as such has approved the compassionate use of the allogeneic MSCs. Stem cell therapy for COVID-19 is under clinical trials with little available data that confirms their safety and efficacy to treat the patients. These cells are being used in seriously ill patients due to unavailability of the specific treatment. MSCs clinical trials have been conducted in various parts of the world including the China, USA and Australia. Available reports of different allogeneic MSCs clinical trials have demonstrated improvement in seriously ill COVID-19 patients. Even COVID-19 patients with liver injury and cytokine storm too have been demonstrated to improve. At present MSCs approved compassionate (emergency) use is to prevent cytokine storm, however, the potential may go beyond and their applications can offer disease prevention as well.

MSCs as already discussed may not be free of risk. The recent evidences of disseminated intravascular coagulation (DIC) in COVID-19 demands further incites on MSCs applications as few experimental studies have reported intravascular coagulation with intravenous injection of MSCs. The under trial clinical studies vary from each other with respect to the patient inclusion and the doses of the cells given. The evaluation criteria need to be extensive, effective and uniform among the studies to develop evidence based medicine. It can be concluded that currently stem cell therapy for COVID-19 is under clinical trials and all the queries related to their safety, feasibility and efficacy need to be confirmed to arrive at any conclusion(s).

Dr Mudasir Bashir Gugjoo is Assistant Professor /Principal Investigator, Stem Cell Research Project FVSc & AH, SKUAST-Kashmir

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