The clinical efficacy and safety of mesenchymal stromal cells for patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

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.

The effect of intravenous immunoglobulins on the outcomes of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Severe-to-critical COVID-19 has been associated with exaggerated immune responses, and anti-inflammatory agents including corticosteroid and interleukin-6 antagonist have been repurposed as the treatment modality against severe SARS-CoV-2 infections. However, the clinical efficacy and safety of intravenous immunoglobulin (IVIG) in the treatment of patients with COVID-19 was controversial. METHODS: This meta-analysis of randomized controlled trials (RCTs) investigated the effectiveness of IVIG in patients with COVID-19. Electronic databases were searched for RCTs that compared the clinical efficacy of IVIG with standard of care or placebo in the hospitalized patients with COVID-19 were included. RESULTS: Six RCTs involving 472 patients were included. Patients who received IVIG had a similar mortality rate to the controls (25.3% vs 27.0%, odds ratio [OR], 0.60; 95% confidence interval [CI], 0.27-1.31). Compared with the control group, the study group demonstrated a similar incidence of receiving mechanical ventilation (OR, 0.70; 95% CI, 0.45-1.11), intensive care unit (ICU) admission (OR, 0.58; 95% CI, 0.22-1.53), length of hospital stay (mean difference [MD], -1.81 days; 95% CI, -8.42 to 4.81) and ICU stay (MD, -0.61 days; 95% CI, -2.80 to 1.58). CONCLUSIONS: The administration of IVIG in hospitalized patients with COVID-19 does not improve clinical outcomes.

Effect of sofosbuvir-based treatment on clinical outcomes of patients with COVID-19: a systematic review and meta-analysis of randomised controlled trials.

This systematic review and meta-analysis examined the efficacy of sofosbuvir-based antiviral treatment against COVID-19 (coronavirus disease 2019). PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched from inception to 15 August 2021. Studies comparing the clinical efficacy and safety of sofosbuvir-based antiviral regimens (study group) with other antivirals or standard of care (control group) in patients with COVID-19 were included. Overall, 687 patients with COVID-19 were included, of which 377 patients received sofosbuvir-based treatment. Mortality was lower in the study group than in the control group [odds ratio (OR) = 0.49, 95% confidence interval (CI) 0.30-0.79; I2 = 0%]. The overall clinical recovery rate was higher in the study group than in the control group (OR = 1.82, 95% CI 1.20-2.76; I2 = 28%). The study group presented a lower requirement for mechanical ventilation (OR = 0.33, 95% CI 0.13-0.89; I2 = 0%) and intensive care unit admission (OR = 0.42, 95% CI 0.25-0.70; I2 = 0%) than the control group. Furthermore, the study group exhibited a shorter hospital length of stay [mean deviation (MD), -1.49, 95% CI -2.62 to -0.37; I2 = 56%] and recovery time (MD, -1.34, 95% CI -2.29 to -0.38; I2 = 46%) than the control group. Sofosbuvir-based treatment may help reduce mortality in patients with COVID-19 and improve associated clinical outcomes. Furthermore, sofosbuvir-based treatment was as safe as the comparator in patients with COVID-19. However, further large-scale studies are warranted to validate these findings.

Clinical efficacy and safety of interferon-ß-containing regimens in the treatment of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this systematic review and meta-analysis of randomized controlled trials(RCTs) was to investigate the efficacy of interferon (IFN)-ß-containing regimens in treating patients with COVID-19. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to 17 July 2021. RCTs comparing the clinical efficacy and safety of IFN-ß-containing regimens (study group) to other antiviral treatment options or placebo (control group) in treating patients with COVID-19 were included. RESULTS: Eight RCTs were included. No significant difference in the 28-day all-cause mortality rate was observed between the study and control groups (OR, 0.74; 95% CI, 0.44-1.24; I2 = 51%). The study groups had a lower rate of intensive care unit (ICU) admissions than the control groups (OR 0.58, 95% CI 0.36-0.95; I2 = 0%). Furthermore, INF-ß was not associated with an increased risk of any adverse event (AE) or serious AE when compared with the control group. CONCLUSIONS: IFN-ß does not appear to provide an increased survival benefit in hospitalized patients with COVID-19 but may help reduce the risk of ICU admission. Moreover, IFN-ß is a safe agent for use in the treatment of COVID-19.

Clinical efficacy and safety of Janus kinase inhibitors for COVID-19: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to investigate the clinical efficacy and safety of Janus kinase (JAK) inhibitors for COVID-19 patients. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to July 12, 2021. RCTs comparing the clinical efficacy and safety of JAK inhibitors with a placebo or standard care in treating COVID-19 patients were included. The primary outcome was all-cause mortality rate at day 28. RESULTS: Three RCTs were included in this meta-analysis. The all-cause mortality rate at day 28 was lower among the patients receiving JAK inhibitors than among the controls (4.1% [28/647] versus 7.0% [48/684], OR, 0.57; 95% CI, 0.36-0.92, I2 = 0). The clinical recovery rate was higher among the patients receiving JAK inhibitors than among the controls (85.1% (579/680) versus 80.0% [547/684], OR, 1.45; 95% CI, 1.09-1.93, I2 = 0). Additionally, the use of JAK inhibitors was associated with a shorter time to recovery than among the controls (MD, -2.84; 95% CI, -5.56 to -0.12; I2 = 50%). The rate of invasive mechanical ventilation (MV) was lower in the patients who used JAK inhibitors than among the controls. Finally, no significant difference was observed between the patients who used JAK inhibitors and the controls in the risk of any adverse events (OR, 0.92; 95% CI, 0.64-1.34; I2 = 33%) and serious adverse events (OR, 0.80; 95% CI, 0.45-1.44; I2 = 46%). CONCLUSIONS: JAK inhibitors can lead to a better clinical outcome of hospitalized COVID-19 patients, and they are a safe agent in the treatment of COVID-19.