Mesenchymal stromal cells (MSCs) have significant immunomodulatory and tissue repair capabilities, mediated partly by conditioned media or through secreted extracellular vesicles (MSC-EVs). Infection with SARS-CoV-2 can cause mild to life-threatening illness due to activated immune responses that may be dampened by MSCs or their secretome. Many clinical studies of MSCs have been launched since the beginning of the global pandemic, however, few have been completed and most lack power to assess efficacy. Repeated systematic searches and meta-analyses are needed to understand, in real time, the extent of potential benefit in different patient populations as the evidence emerges.


This living systematic review will be maintained to provide up-to-date information as the pandemic evolves. A systematic literature search of Embase, MEDLINE, and Cochrane Central Register of Controlled Trials databases will be performed. All clinical studies (e.g., randomized, pseudorandomized and non-randomized controlled trials, uncontrolled trials, and case series) employing MSCs or their secretome as a therapeutic intervention for COVID-19 will be included. Patients must have confirmed SARS-CoV-2 infection. Study screening and data extraction will be performed in duplicate. Information concerning interventions, patient populations, methods of MSC isolation and characterization, primary and secondary clinical and/or laboratory outcomes, and adverse events will be extracted. Key clinical outcomes will be pooled through random-effects meta-analysis to determine the efficacy of MSCs and their secreted products for COVID-19.


Our systematic review and subsequent updates will inform the scientific, medical, and health policy communities as the pandemic evolves to guide decisions on the appropriate use of MSC-related products to treat COVID-19.

Systematic review registration:

PROSPERO CRD 42021225431.


ARDS; Acute respiratory distress syndrome; COVID-19; Coronavirus disease 2019; Exosomes; Extracellular vesicles; MSCs; Mesenchymal stem cells; Mesenchymal stromal cells; Microvesicles; Pneumonia; SARS-CoV-2; Sepsis; Severe acute respiratory syndrome coronavirus 2.