MESENCHYMAL STEM CELL TREATMENT FOR COVID-19: A 2021 UPDATE

BACKGROUND: COVID-19 is an infectious disease characterized by a strong inflammatory response in severe cases. Treatment is limited, and mortality has surpassed 2.4 million deaths as in February, 2021. Therefore, several different therapeutic strategies are being investigated, including the use of mesenchymal stem cells (MSCs). Our group has previously published an analysis of the world-wide effort to investigate the use of stem cells for COVID-19 in July 2020 (Saldanha-Araújo, 2020). Here, we provide an update to such a compendium of clinical trials. METHODS: Using the terms “COVID-19” and “stem cells”, we searched studies in the ClinicalTrials.gov database, the World Health Organization‘s International Clinical Trials Registration Platform, and the European Union Registry of Clinical Trials in June 2020 and February 2021. RESULTS: A total of 119 clinical studies was considered, among which 99 studies aim to investigate the therapeutic efficacy of MSCs and derivatives in the treatment of COVID-19. The country with the higher number of studies was China. The most frequent tissue sources of MSCs were: umbilical cord; Wharton‘s Jelly, bone marrow, and adipose tissue. Six studies used MSC-derived exosomes. Most studies chose the intravenous route for cell therapy administration, but the inhalation route was also observed. Cell doses ranged between 0.5 × 10(6) and 1 × 10(7) cells/kg. Number of doses varied from 1 to 20 (twice/day inhalation for 10 days). Most studies are still in the recruitment process, and 2 have completed their studies and published their data. Several studies failed to describe MSC tissue source, administration route, and/or study phase. CONCLUSION: Taken together, the present data reveals that stem cells and stem cell-derived strategies are still experimental therapies for COVID-19 treatment. Since July 2020, only one new scientific manuscript has been published describing clinical results from stem cell therapy for COVID-19. Similar to July 2020, published studies show that 51 patients received stem cell and stem cell-derived therapies and support the notion that the procedure is safe and effective in the short term for severe and critically ill patients. Long term follow-up and optimization of therapeutic regimen are still needed. The lack of complete detailed data from published studies are a challenge and compromise any further conclusions at this point.