Coronavirus disease-19 (COVID-19) is a zoonotic disease that has become a global pandemic. The fast evolution of the COVID-19 pandemic and persist problems make COVID-19 highly infectious; publicly accessible literature and other sources of information continue to expand in volume. The mesenchymal stem cells (MSCs) therapy efficacy for COVID-19 is debatable. This systematic review and meta-analysis (SRMA) aimed to evaluate the usefulness of MSCs in treating COVID-19. Relevant publications were retrieved from databases up to April 30, 2022. In the case of dichotomous data, the 95% confidence intervals (CIs) and pooled risk ratio (RR) were estimated with a random effects model (REM) or fixed effects model (FEM). The pooled mean difference (MD) and 95% CIs were calculated with REM or FEM in continuous data. In the outcomes, studies with insufficient or unusable data were reported descriptively. A total of eight randomized controlled trials (RCTs) with 464 people were chosen for this SRMA. Relative to the control group, mortality was significantly lower in the MSCs group (RR: 0.66, 95% CI: 0.44, 0.99, Z = 2.01, p = .04); other secondary outcomes, such as the clinical symptom improvement rate improved in the MSCs group (RR: 1.44, 95% CI: 1.05, 1.99, Z = 2.24, p = .03), clinical symptom improvement time (MD: -4.01, 95% CI: -6.33, -1.68, Z = 3.38, p = .0007), C-reactive protein (CRP) (MD: -39.16, 95% CI: -44.39, -33.94, Z = 14.70, p < .00001) and days to hospital discharge (MD: -3.83, 95% CI: -6.19, -1.48, Z = 3.19, p = .001) reduced significantly in MSCs group. However, the adverse reaction incidence did not change significantly. MSCs are a viable therapy option for COVID-19 because of their safety and potential efficacy. With no significant adverse effects, MSCs can reduce mortality, clinical symptom improvement time, and days to hospital discharge, improve clinical symptoms, and reduce inflammatory cytokines CRP in COVID-19. However, further high-quality clinical studies are required to confirm these results.
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