In patients with critical manifestations of COVID-19, life-threatening complications such as ARDS and multiple organ dysfunction are mediated by extensive inflammation, neutrophils recruitment, cytokine storm syndrome and dysregulated immune innate responses.

MSCs because of their immunomodulatory, regenerative, and antimicrobial properties could render several therapeutic effects in the setting of COVID-19. While data from countless clinical studies have established that MSCs are safe, the data with regards to MSC efficacy hasn’t been as conclusive.

In this review are discussed at length the beneficial effects of MSCs as it
relates to their immunomodulatory, regenerative and antimicrobial nature.

However, it is important to note that the majority of these findings were delineated in studies conducted in vitro, and in vivo models. As highlighted above, recapitulation of efficacy data obtained in animal models in human subjects remains a major barrier to successful translation of MSC therapy in clinical settings.

This is even more relevant in the setting of COVID-19, as there is no pre-clinical efficacy data for the use of MSC in animal models of COVID-19 pneumonia. These pre-clinical studies are crucial, as they can provide valuable information on the consequences, both beneficial and deleterious of MSC administration specifically in the context of COVID-19 pneumonia.

Even in the absence of pre-clinical data specific to MSCs and COVID-19, MSCs have already been administered to COVID-19 subjects and there are multiple ongoing trials for use of MSCs in these patients.

The data from the initial studies suggest that MSC administration to subjects with COVID-19 pneumonia is associated with alleviation of disease symptoms.
As depicted in the review, for the ongoing and proposed clinical studies, there is considerable variation is terms of cell source and dosing regimen. Though administration of MSCs have already been associated with positive outcomes in COVID-19 subjects, best practices as it relates to formulation, cell source, dosing regimen and timing has not been established. These clinical studies evaluating MSCs in COVID-19 subjects could resolve some of
these key issues. Pre-clinical studies in relevant animal models of COVID-19 pneumonia could also assist in answering these questions.

The safety of MSCs, the extensive pre-clinical efficacy data relating to their use in conditions with pathophysiologies analogous to that of COVID-19 pneumonia, and the initial reports of positive clinical indicators in response to MSC treatment in human cohorts with COVID-19, leads us to believe that MSCs are a potentially beneficial therapeutic option for COVID-19 subjects
with critical manifestations of the disease which is governed by a hyper-inflammatory state.

While it’s supposed that MSC therapy may be potentially beneficial in this setting, it’s necessary to emphasize that MSCs cannot and should not be viewed as a panacea for COVID-19 and that administration of MSCs should not occur in the absence of grave disease complications such as hypoxic respiratory failure and ARDS, and only in the context of an approved clinical trial at no cost to the subjects.