The COVID-19 pandemic has placed an unprecedented burden on health care systems and economies around the globe. Clinical evidences demonstrate that SARS-CoV-2 infection produces detrimental levels of pro-inflammatory cytokines and chemokines that can lead to acute respiratory distress syndrome (ARDS) and significant systemic organ damage. Currently, there is no definitive therapy for COVID-19 or associated complications, and with the hope of a safe and effective vaccine in the distant future, the search for an answer is paramount. Mesenchymal stem cells (MSCs) provide a viable option due to their immunomodulatory effects and tissue repair and regeneration abilities. Studies have demonstrated that compassionate use of MSCs can reduce symptoms associated with SARS-CoV-2 infection, eliminate fluid buildup, and act as a regenerative technique for alveolar damage; all in a safe and effective way. With multiple autologous sources available for MSCs, each with their own respective limitations, allogenic umbilical cord (UC) and/or UC-derived Wharton's jelly (WJ) seem to be best positioned source to harvest MSCs to treat COVID-19 and associated symptoms. As an allogenic source, UC is readily available, easily obtainable, and is rich in immunomodulatory and regenerative factors. In this manuscript, we reviewed the current evidences and explored the potential therapeutic use of allogenic UC and/or WJ-derived MSCs for the treatment of COVID-19. Although, preliminary preclinical and clinical studies indicate that their use is safe and potentially effective, more multi-center, randomized, controlled trials are needed to adequately assess the safety and efficacy of UC and/or WJderived MSCs for the treatment of COVID-19.

The global SARS-CoV-2 outbreak has been accompanied with severe socio-economic and health burdens that will ripple through history. It is now known that SARS-CoV-2 induces a cytokine storm that leads to acute respiratory distress syndrome and systemic organ damage. With no definitive nor safe therapy for COVID-19 as well as the rise of viral variants the need for an urgent treatment modality is paramount. Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) have long been praised for their anti-viral, anti-inflammatory and tissue regenerative capabilities. MSCs and their EVs are now being studied for their possible use as a treatment modality for COVID-19. In this review we explore their capabilities and outline the evidence of their use in ALI, ARDS and COVID-19.

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