Abstract
Background: Mesenchymal stem/stromal cells (MSCs) and their secreted products are a promising therapy for COVID-19 given their immunomodulatory and tissue repair capabilities. Many small studies were launched at the onset of the pandemic, and repeated meta-analysis is critical to obtain timely and sufficient statistical power to determine efficacy.
Methods and findings: All English-language published studies identified in our systematic search (up to February 3, 2021) examining the use of MSC-derived products to treat patients with COVID-19 were identified. Risk of bias (RoB) was assessed for all studies. Nine studies were identified (189 patients), four of which were controlled (93 patients). Three of the controlled studies reported on mortality (primary analysis) and were pooled through random-effects meta-analysis. MSCs decreased the risk of death at study endpoint compared with controls (risk ratio, 0.18; 95% confidence interval [CI], 0.04 to 0.74; P = .02; I 2 = 0%), although follow-up differed. Among secondary outcomes, interleukin-6 levels were most commonly reported and were decreased compared with controls (standardized mean difference, -0.69; 95% CI, -1.15 to -0.22; P = .004; I 2 = 0%) (n = 3 studies). Other outcomes were not reported consistently, and pooled estimates of effect were not performed. Substantial heterogeneity was observed between studies in terms of study design. Adherence to published ISCT criteria for MSC characterization was low. In two of nine studies, RoB analysis revealed a low to moderate risk of bias in controlled studies, and uncontrolled case series were of good (3 studies) or fair (2 studies) quality.
Conclusion: Use of MSCs to treat COVID-19 appears promising; however, few studies were identified, and potential risk of bias was detected in all studies. More controlled studies that report uniform clinical outcomes and use MSC products that meet standard ISCT criteria should be performed. Future iterations of our systematic search should refine estimates of efficacy and clarify potential adverse effects.
Keywords: COVID-19; SARS-CoV-2; acute respiratory distress syndrome; coronavirus disease 2019; exosomes; extracellular vesicles; mesenchymal stem cells; mesenchymal stromal cells; microvesicles; pneumonia; sepsis; severe acute respiratory syndrome coronavirus 2.
【저자키워드】 COVID-19, SARS-CoV-2, Coronavirus disease 2019, acute respiratory distress syndrome, Pneumonia, Mesenchymal stromal cells, Sepsis, Mesenchymal stem cells, Extracellular vesicles, Exosomes, Microvesicles, Severe acute respiratory syndrome coronavirus 2., 【초록키워드】 coronavirus disease, Meta-analysis, Respiratory distress syndrome, Coronavirus disease 2019, Efficacy, coronavirus, pandemic, Mortality, acute respiratory distress syndrome, Mesenchymal stromal cells, adherence, interleukin-6, risk, Sepsis, Mesenchymal stem cells, MSCs, Extracellular vesicles, Exosomes, Microvesicles, severe acute respiratory syndrome Coronavirus, heterogeneity, Clinical outcome, adverse effects, immunomodulatory, Control, Study design, Statistical power, Follow-up, estimate, Critical, moderate, patients, tissue repair, acute respiratory distress, Analysis, MSC, risk ratio, criteria, respiratory distress, stromal cells, not performed, risk of death, acute respiratory syndrome, Endpoint, standardized mean difference, 95% CI, acute respiratory syndrome coronavirus, Other outcomes, acute respiratory syndrome coronavirus 2, 95% confidence interval, Secondary outcomes, potential risk, treat, primary analysis, random-effects, Future, repeated, Cell, Extracellular, ISCT, performed, reported, nine, case sery, appear, determine, iteration, Other outcome, patients with COVID-19, random-effect, risk of bia, RoB, secreted, therapy for COVID-19, 【제목키워드】 systematic review, Cell-based therapy, MSC,