Re: “Exosomes Derived from Bone Marrow Mesenchymal Stem Cells as Treatment for Severe COVID-19” by Sengupta et al.

T he catastrophic COVID-19 pandemic demands urgent development and testing of potential new therapeutics.However, these need to be developed in a transparent way including rigorous peer-reviewed and appropriately conducted, regulated, and reported clinical investigations.Recently, Sengupta et al. reported on intravenous application of exosomes in 24 patients suffering from COVID-19 with moderate-to-severe acute respiratory distress syndrome [1].Although we welcome rigorous investigations of extracellular vesicles (EVs) in this setting, key details were lacking that allow adequate assessment of the medical value and scientific rationale of this study.Specifically, little information was provided about the investigational new drug ''ExoFloÔ,'' including EV characterization, biological properties, and proposed biological or therapeutic actions.The website of one manufacturer offering ExoFlo (''Direct Biologics'') (https://directbiologics.com/#aboutus) does not provide this information and there are no other obvious sources of the relevant product details.Although we understand that ExoFlo was produced under current good manufacturing practice (cGMP) conditions in an U.S. Food and Drug Administration (FDA)-certified and inspected facility, it is not clear as to what was actually being administered to the patients.The information provided in the article is thus insufficient for critical analyses and comprehension of the results as well as for potential replication of the investigation.We, therefore, request clarification of the following points regarding the ExoFlo product and application: