The clinical efficacy and safety of mesenchymal stromal cells for patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials
Ontology highlight
ABSTRACT: Objectives
This meta-analysis of randomized controlled trials (RCTs) investigated the usefulness of mesenchymal stromal cells (MSCs) to treat patients with COVID-19. Methods: PubMed, Embase, Ovid MEDLINE, the Cochrane Library, and Clinicaltrials.gov were searched for RCTs published before November 7, 2021. Only RCTs that compared the clinical efficacy and safety of MSCs with other alternative treatments or placebos in the treatment of patients with COVID-19 were included. Results
Six RCTs were included, in which the MSC and control groups consisted of 158 and 135 patients, respectively. The patients who received MSCs had a significantly lower 28-day mortality rate (7.6% vs 21.5%; OR, 0.18; 95% CI, 0.06-0.52; I2 = 0%) and significantly higher clinical improvement rate (OR, 6.05; 95% CI, 2.31-15.83; I2 = 0%) than the controls. The patients who received MSCs were associated with a similar risk of adverse events (AEs) and serious AEs to the control group (AEs: OR, 33; 95% CI, 0.09-1.18; I2 = 59%; serious AEs: OR, 0.30; 95% CI, 0.02-4.41; I2 = 53%). Conclusions
MSC treatment may help to improve the clinical outcomes of patients with COVID-19. In addition, MSC treatment appears to be a safe therapeutic option for patients with COVID-19.
SUBMITTER: Chen C
PROVIDER: S-EPMC9259515 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Mesenchymal stromal cells (MSC) have shown potential efficacy in both animal and human trials of acute respiratory distress syndrome (ARDS). Especially during the COVID-19 pandemic, MSC was intensely studied for treating COVID-19-induced ARDS. The purpose of this study is to evaluate the safety and efficacy of MSC in ARDS via a meta-analysis of randomized controlled trials (RCTs). Therefore, a meta-analysis of RCTs of MSC as a therapy for ARDS was conducted. The protocol of this review was registered on Open Science Framework. With no language restriction and according to the "PICOs" principle, searches were conducted on Pubmed and Embase to retrieve any clinical literature on MSC for ARDS. Any RCT, which compared MSC to controls for ARDS, where MSC and controls were intravenously infused, of any dosage, was eligible for inclusion. A total of 13 RCTs, which evaluated MSC versus control for treating ARDS, enrolling a total of 655 cases, met the inclusion criteria and appeared in this meta-analysis. A heterogeneity assessment was carried out using the χ2 test, where a P value less than 0.05 was considered significant. The choice of a fixed-effect or a random-effect model was decided by the I2 value in each of the analyses. This meta-analysis indicated that there was no significant difference in terms of adverse events between MSC and control for ARDS (OR = 0.64, 95% CI [0.34, 1.20], P = 0.17, and I2 = 0%). In comparison with control, MSC could reduce the mortality of ARDS (OR = 0.66, 95% CI [0.46, 0.96], P = 0.03, and I2 = 10%). Based on the results of our meta-analysis, the safety of MSC was demonstrated to be non-inferior to that of standard treatment, and MSC may reduce the mortality rate of ARDS. Though the heterogeneity in the main results was low (I2 < 25%), more high-quality and large-scale clinical trials are needed to further confirm our findings.
| S-EPMC9857915 | biostudies-literature
Project description:The benefits and harms of corticosteroids for patients with severe coronavirus disease 2019 (COVID-19) remain unclear. We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials from December 31, 2019 to October 1, 2020 to identify randomized controlled trials (RCTs) that evaluated corticosteroids in severe COVID-19 patients. The primary outcome was all-cause mortality at the longest follow-up. Secondary outcomes included a composite disease progression (progression to intubation, ventilation, extracorporeal membrane oxygenation, ICU transfer, or death among those not ventilated at enrollment) and incidence of serious adverse events. A random-effects model was applied to calculate risk ratio (RR) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation approach to evaluate the certainty of the evidence. Seven RCTs involving 6250 patients were included, of which the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial comprised nearly 78% of all included subjects. Results showed that corticosteroids were associated with a decreased all-cause mortality (27.3 vs. 31.1%; RR: 0.85; 95% CI: 0.73-0.99; P = 0.04; low-certainty evidence). Trial sequential analysis suggested that more trials were still required to confirm the results. However, such survival benefit was absent if RECOVERY trial was excluded (RR: 0.83; 95% CI: 0.65-1.06; P = 0.13). Furthermore, corticosteroids decreased the occurrence of composite disease progression (30.6 vs. 33.3%; RR: 0.77; 95% CI: 0.64-0.92; P = 0.005), but not increased the incidence of serious adverse events (3.5 vs. 3.4%; RR: 1.16; 95% CI: 0.39-3.43; P = 0.79).
| S-EPMC7897363 | biostudies-literature
Project description:BackgroundMesenchymal stromal cells (MSCs) are used as an emerging new option for the treatment of knee osteoarthritis (OA). However, their efficacy remains controversial across studies with different doses of MSCs and cell processing methods. We conducted this meta-analysis to assess the efficacy of MSCs in the treatment of knee OA.MethodsRandomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, SinoMed (Chinese BioMedical Literature Service System, China), and CNKI (National Knowledge Infrastructure, China) databases were systematically reviewed. The pain level and function improvements were evaluated using visual analog scale (VAS), McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC). The pooled estimate was calculated with weighted mean difference (WMD) with 95% confidence intervals (95%CIs).ResultsNine RCTs involving 476 patients were included in this meta-analysis. The pooled estimate showed that the treatment of MSCs significantly reduced VAS, WOMAC pain, WOMAC stiffness, and WOMAC function scores at a long-term follow-up (12 or 24 months). However, for the IKDC and WOMAC total scores, MSCs also showed significant improvement in these outcomes, although this was not statistically significant when compared to the control.ConclusionBased on the current studies, our results suggested that MSCs were a promising option for the treatment of patients with knee OA. However, considering the potential limitations, more well-performed, large-scale RCTs are needed to verify our findings.
| S-EPMC7789676 | biostudies-literature
Project description:BackgroundElevated levels of inflammatory factors are associated with poor prognosis in coronavirus disease-19 (COVID-19). However, mesenchymal stem cells (MSCs) have immunomodulatory functions. Accordingly, this meta-analysis aimed to determine the efficacy and safety of MSC-based therapy in patients with COVID-19 pneumonia.MethodsOnline global databases were used to find relevant studies. Two independent researchers then selected and evaluated the studies for suitability while the Cochrane risk of bias tool determined the quality of all articles and Cochran's Q test and I2 index assessed the degree of heterogeneity in the principal studies. Statistical analysis was performed using Review Manager software, and the effect of each study on the overall estimate was evaluated by sensitivity analysis.ResultsSeven studies were included in the meta-analysis, and all MSCs used in the trials were acquired from the umbilical cord. The results of these studies (n = 328) indicated that patients with COVID-19 pneumonia who received MSCs had a 0.58 risk of death compared with controls (95% CI = 0.38, 0.87; P = 0.53; I2 = 0%). In terms of inflammatory biomarkers, MSCs reduced the levels of C-reactive protein (n = 88; MD = - 32.49; 95% CI = - 48.43, - 16.56; P = 0.46; I2 = 0%) and interferon-gamma (n = 44; SMD = - 1.23; 95% CI = - 1.89, - 0.57; P = 0.37; I2 = 0%) in severe COVID-19 patients but had no significant effect on interleukin-6 (n = 185; MD = - 0.75; 95% CI = - 7.76, 6.27; P = 0.57; I2 = 0%). A summary of the data revealed no significant differences in adverse events (n = 287) or serious adverse events (n = 229) between the MSC and control groups.ConclusionsInfusion of umbilical cord-derived MSCs is an effective strategy for treating patients with COVID-19 pneumonia, with no noticeable adverse effects.
| S-EPMC10159228 | biostudies-literature
Project description:Oncolytic virotherapy is a promising antitumor therapeutic strategy. It is based on the ability of viruses to selectively kill cancer cells and induce host antitumor immune responses. However, the clinical outcomes of oncolytic viruses (OVs) vary widely. Therefore, we performed a meta-analysis to illustrate the efficacy and safety of oncolytic viruses. The Cochrane Library, PubMed, and EMBASE databases were searched for randomized controlled trials (RCTs) published up to January 31, 2020. The data for objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were independently extracted by two investigators from 11 studies that met the inclusion criteria. In subgroup analyses, the objective response rate benefit was observed in patients treated with oncolytic DNA viruses (odds ratio (OR) = 4.05; 95% confidence interval (CI): 1.96-8.33; p = 0.0002), but not in those treated with oncolytic RNA viruses (OR = 1.00, 95% CI: 0.66-1.52, p = 0.99). Moreover, the intratumoral injection arm yielded a statistically significant improvement (OR = 4.05, 95% CI: 1.96-8.33, p = 0.0002), but no such improvement was observed for the intravenous injection arm (OR = 1.00, 95% CI: 0.66-1.52, p = 0.99). Among the five OVs investigated in RCTs, only talimogene laherparepvec (T-VEC) effectively prolonged the OS of patients (hazard ratio (HR), 0.79; 95% CI: 0.63-0.99; p = 0.04). None of the oncolytic virotherapies improved the PFS (HR = 1.00, 95% CI: 0.85-1.19, p = 0.96). Notably, the pooled rate of severe AEs (grade ?3) was higher for the oncolytic virotherapy group (39%) compared with the control group (27%) (risk difference (RD), 12%; risk ratio (RR), 1.44; 95% CI: 1.17-1.78; p = 0.0006). This review offers a reference for fundamental research and clinical treatment of oncolytic viruses. Further randomized controlled trials are needed to verify these results.
| S-EPMC7352817 | biostudies-literature
Project description:IntroductionMany immunomodulators have been studied in clinical trials for the treatment of coronavirus disease 2019 (COVID-19). However, data identifying the most effective and safest treatment are lacking. We conducted a systematic review and network meta-analysis to rank immunomodulators in the treatment of COVID-19 according to their efficacy and safety.MethodsPublished and peer-reviewed randomized controlled trials assessing the efficacy of immunomodulators in hospitalized patients with COVID-19 were searched up to June 30, 2021. Direct and network meta-analyses were applied to assess the outcomes. The probability of efficacy and safety was estimated, and the drugs were awarded a numerical ranking.ResultsTwenty-six studies were eligible. Compared with standard of care, dexamethasone and tocilizumab had significantly lower mortality rates with pooled risk ratios (RRs) of 0.91 (95% confidence interval [CI] 0.84-0.99) and 0.88 (95% CI 0.82-0.96), respectively. Meanwhile, the most effective corticosteroid, interleukin-6 antagonist, and Janus kinase (JAK) inhibitor were hydrocortisone, sarilumab, and ruxolitinib, respectively. However, when superimposed infection was considered, ruxolitinib was the best treatment followed by baricitinib. Moreover, methylprednisolone had the worst combined efficacy and safety among the examined treatments.ConclusionsOverall, immunomodulators were more effective than standard of care. Important differences exist among immunomodulators regarding both efficacy and safety in favor of ruxolitinib and baricitinib. Further well-conducted randomized controlled trials should focus on JAK inhibitors. Methylprednisolone use should be discouraged because of its poor efficacy and high risk of superimposed infection. TRIAL REGISTRATION: PROSPERO registration identifier CRD 42021257421.
| S-EPMC8579415 | biostudies-literature
Project description:BackgroundLopinavir-ritonavir is a repurposed drug for coronavirus disease-2019 (COVID-19). In this study, a pooled effect of lopinavir-ritonavir on mortality, virological cure, radiological improvement and safety profile in COVID-19 patients has been evaluated.MethodsThe databases were searched for comparative randomized controlled studies evaluating the efficacy and/or safety of lopinavir-ritonavir in COVID-19 patients. The mortality outcome was pooled as a risk difference (RD) with 95% CI. The virological cure, radiological improvement and adverse events were pooled as risk ratio (RR) with 95% CI. All outcomes were pooled using the Mantle-Hanzle method random effect model. The heterogeneity was assessed using the I2 test.ResultsOut of 82 full text assessed, seven studies were included in the analysis. The included studies had five different control interventions: supportive care (n=4), umifenovir (arbidol) (n=2), navaferon (recombinant anti-tumour and anti-virus protein) (n=1), lopinavir-ritonavir+novaferon (n=1) and lopinavir-ritonavir+interferon beta 1b+ribavirin (n=1). Lopinavir-ritonavir group did not show significant difference in mortality [RD: 0.00 (95% CI: -0.01, 0.02), I2=0], virological cure [RR: 1.06 (95% CI: 0.85, 1.31), I2=0%], radiological improvement [RR: 0.81 (95% CI: 0.62, 1.05)] and adverse events [RR: 2.59 (95% CI: 0.17, 38.90), I2=75%] than supportive care. Similarly, no difference was observed for any efficacy outcomes between lopinavir-ritonavir and other control interventions. We observed significantly high risk of adverse events with lopinavir-ritonavir as compared to umifenovir [RR: 2.96 (95% CI: 1.42-6.18); I2=0%].ConclusionThere is no benefit of the addition of lopinavir-ritonavir to the standard care in COVID-19 patients.
| S-EPMC8056786 | biostudies-literature
Project description:We conducted meta-analyses of findings from randomized, placebo-controlled, short-term trials for acute mania in manic or mixed states of DSM (III-IV) bipolar I disorder in 56 drug-placebo comparisons of 17 agents from 38 studies involving 10,800 patients. Of drugs tested, 13 (76%) were more effective than placebo: aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperdone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone. Their pooled effect size for mania improvement (Hedges' g in 48 trials) was 0.42 (confidence interval (CI): 0.36-0.48); pooled responder risk ratio (46 trials) was 1.52 (CI: 1.42-1.62); responder rate difference (RD) was 17% (drug: 48%, placebo: 31%), yielding an estimated number-needed-to-treat of 6 (all p<0.0001). In several direct comparisons, responses to various antipsychotics were somewhat greater or more rapid than lithium, valproate, or carbamazepine; lithium did not differ from valproate, nor did second generation antipsychotics differ from haloperidol. Meta-regression associated higher study site counts, as well as subject number with greater placebo (not drug) response; and higher baseline mania score with greater drug (not placebo) response. Most effective agents had moderate effect-sizes (Hedges' g=0.26-0.46); limited data indicated large effect sizes (Hedges' g=0.51-2.32) for: carbamazepine, cariprazine, haloperidol, risperidone, and tamoxifen. The findings support the efficacy of most clinically used antimanic treatments, but encourage more head-to-head studies and development of agents with even greater efficacy.
| S-EPMC3055677 | biostudies-other
Project description:Background/aimsConventional disease-modifying anti-rheumatic drugs have been trialed in osteoarthritis (OA). Hydroxychloroquine (HCQ), which has shown its effectiveness in rheumatoid arthritis, has been trialed for the treatment of OA; however, its efficacy and safety remain unclear. This systematic review and meta-analysis evaluate efficacy and safety of HCQ for the treatment of OA.MethodsMEDLINE, EMBASE, and Cochrane Central were searched from inception through June 2020. Two reviewers independently screened for randomized controlled trials (RCTs) comparing HCQ with placebo or other active-comparators for the treatment of knee, hand, or hip OA, extracted data, and performed Cochrane risk of bias assessments.ResultsSix RCTs, four in hand OA, two in knee OA, consisting of 842 patients (436 in HCQ arm, 406 in control arm) were included. RCTs were conducted between 2012 and 2020, one each at UK, Netherlands, Germany, Italy, Iran, and Egypt; follow-up period ranged 24 to 52 weeks. High-quality evidence showed no clinically important pain reduction with HCQ compared to placebo/active-control in hand OA (standardized mean difference [SMD], 0.14; 95% confidence interval [CI], -0.20 to 0.48). Effect on pain reduction in knee and hand OA was small and non-significant (SMD, -0.09; 95% CI, -0.44 to 0.25). High-quality evidence showed no improvement in dysfunction with HCQ compared to placebo in hand OA patients (SMD, 0.08; 95% CI, -0.23 to 0.40). Effect on dysfunction improvement in knee and hand OA was modest and statistically non-significant (SMD, -0.20; 95% CI,-0.57 to 0.18). No improvement in quality of life was observed in hand OA.ConclusionHCQ has no benefit in reducing pain and improving physical function in hand or knee OA patients.
| S-EPMC8747931 | biostudies-literature
Project description:BackgroundFibromyalgia is a chronic pain syndrome characterized by persistent and widespread musculoskeletal pain. Telerehabilitation is a promising treatment for patients with fibromyalgia through long-term monitoring, intervention, supervision, consultation, and education.ObjectiveThis study aimed to perform a comprehensive systematic review and meta-analysis of the efficacy and safety of telerehabilitation in patients with fibromyalgia.MethodsRandomized controlled trials (RCTs) related to fibromyalgia and telerehabilitation were systematically searched in the PubMed, PEDro, Cochrane Library, ScienceDirect, Ovid MEDLINE, Embase, and Web of Science databases from inception to November 13, 2022. Two independent researchers screened the literatures and evaluated the methodological quality using the Cochrane Risk of Bias Tool. The outcome measures included the Fibromyalgia Impact Questionnaire scale, pain intensity, depression, pain catastrophizing, quality of life (QoL), and adverse events. Pooled effect sizes were calculated by Stata SE 15.1; a fixed effects model was used when I2<50%, whereas a random effects model was used when I2≥50%.ResultsA total of 14 RCTs with 1242 participants were included in this meta-analysis. The pooled results indicated that the telerehabilitation improved the Fibromyalgia Impact Questionnaire score (weighted mean difference -8.32, 95% CI -11.72 to -4.91; P<.001), pain intensity (standardized mean difference [SMD] -0.62, 95% CI -0.76 to -0.47; P<.001), depression levels (SMD -0.42, 95% CI -0.62 to -0.22; P<.001), pain catastrophizing (weighted mean difference -5.81, 95% CI -9.40 to -2.23; P=.001), and QoL (SMD 0.32, 95% CI 0.18 to 0.47; P<.001) in patients with fibromyalgia compared to control interventions. Only 1 RCT reported a mild adverse event of telerehabilitation; the other 13 RCTs did not mention this.ConclusionsTelerehabilitation can improve the symptoms and QoL of fibromyalgia. However, the safety of telerehabilitation remains uncertain due to the lack of sufficient evidence for the management of fibromyalgia. More rigorously designed trials are needed in the future to verify the safety and efficacy of telerehabilitation in fibromyalgia.Trial registrationPROSPERO CRD42022338200; https://tinyurl.com/322keukv.
| S-EPMC10170363 | biostudies-literature