Cell-based therapies for coronavirus disease 2019: proper clinical investigations are essential

Abstract

The serious consequences of the global COVID-19 pandemic have prompted a rapid gobal response to develop effective therapies that can lessen disease severity in infected patients.Cell-based approaches, primarily using mesenchymal stromal cells (MSCs), have demonstrated a strong safety profile and possible efficacy in patients with the acute respiratory distress syndrome (ARDS), but whether these therapies are effective for treating respiratory virus-induced ARDS is unknown. According to the WHO ICTRP and the NIH clinicaltrials.gov databases, 27 clinical investigations of MSC-based cell therapy approaches have begun in China since the onset of the COVID-19 outbreak, as well as a growing number of academic and industry trials elsewhere. Several recent published reports have suggested potential efficacy; however, the available data presented is either anecdotal or from incomplete, poorly controlled investigations. Therefore, while there may be a potential role for MSCs and other cell-based therapies in treatment of COVID-19, these need to be investigated in a rationally designed, controlled approach if safety and efficacy are to be demonstrated accurately. We urge that the field proceeds by finding balance between swift experimentation and communication of results, and scientifically coherent generation and analysis of clinical data.

The role of mesenchymal stromal cells in immune modulation of COVID-19: focus on cytokine storm

“…It should be mentioned that just a few cell therapy studies for ARDS and sepsis have reached their primary goals in randomized investigations [81,82]. Scientists approve that targeted clinical research is essential whilst the first reports of MSC use for COVID-19 over the early phase of COVID-19 breakout in China have presented valuable clues that the therapeutic measures could be rather safe and efficient [83][84][85]. Few conclusions can be derived from these early studies because of the low number of subjects (typically ≤ 10) and the absence of adequate control groups [58,80,86].…”

Mesenchymal Stromal Cells in Viral Infections: Implications for COVID-19

“…A very recent position review from research leaders of the International Society of Cellular and Gene Therapies (ISCT) has considered that there may be a potential role for MSCbased therapy in COVID-19, however, rationally designed and controlled clinical approaches are needed to demonstrate accurately its safety and therapeutic efficacy [131].…”

“…In conclusion, the perspective of treating viral infection diseases, including COVID-19 and other emergent respiratory tract viral infections, with MSCs may be promising. However, strict patient inclusion/exclusion criteria should be defined, well-designed and controlled clinical trial should be performed and rigorous ethical considerations must ensure patient safety [5,106,107,130,131]. Moreover, development of priming protocols to improve MSC quality attributes for clinical application in viral infections should be considered [103,105,122].…”

The rising role of mesenchymal stem cells in the treatment of COVID-19 infections

“…Since January 2020, several reports have been published on the success of MSC therapies in the treatment of COVID-19 complications in conjunction with other therapeutic modalities [65][66][67][68]. There are two published studies from China on the use of MSCs in the treatment of COVID-19: one included 7 patients and the second one was a single case report [65][66][67]. Recently, 2 commercial companies; Pluristem and Mesoblast; made press releases announcing their preliminary results on the use of MSCs in the treatment of patients having severe COVID-19 [54,69,70].…”

“…Currently, MSCs are being tested in several clinical trials including: NCT04269525, NCT04288102, and NCT04252118 [57,67,71,72].…”