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1.
EClinicalMedicine ; 51: 101545, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1926374

ABSTRACT

Background: The present study aims to better understand the efficacy and safety of mesenchymal stromal cells (MSCs) in treating severe/critical patients with COVID-19. Methods: PubMed, the Cochrane Library, and the Chinese electronic database CNKI were searched from inception up to Dec 19, 2021. Original comparative studies for MSC treatment + standard treatment for severe/critical patients with COVID-19, with placebo or standard treatment as the control group, were included. The primary outcomes were in-hospital mortality and adverse events (AEs). A meta-analysis was performed to compare the mortality rates between the two groups. Then, a subgroup analysis was performed according to the category of the disease (severe or critical) and MSC dose. Afterwards, a descriptive analysis was performed for AEs and secondary outcomes. The funnel plot and Egger's test were used for the publication bias assessment. Findings: Compared to placebo or standard care, MSCs provide significant benefit in the treatment of patients with severe/critical COVID-19, in terms of in-hospital mortality rate (odds ratio: 0.52, 95% CI 0.32-0.84), with very low heterogeneity (P=0.998 [Q test], I 2=0.0%) and less AEs. No significant difference was found in mortality rate due to the different disease categories or MSC doses. Furthermore, no publication bias was found. Interpretation: The present study demonstrates that MSCs are highly likely to reduce mortality and are safe to use for patients with severe or critical COVID-19, regardless of whether 1-3 doses are applied. However, due to the small sample size of the included studies, further high-quality, large-scale trials are needed to confirm this statement in the future. Funding: The National Key Research and Development Program of China (No. 2020YFC0860900), the Science and Technology Project of Wuhan (No. 2020020602012112), the Tianjin Science and Technology Research Program (18PTSYJC00070 and 16PTWYHZ00030), Haihe Laboratory of Cell Ecosystem Innovation Fund (HH22KYZX0046), and the Tianjin Free Trade Zone Innovation Development Project (ZMCY-03-2021002-01) funded the study. We are also grateful for the support from the 3551 Talent Plan of China Optics Valley.

2.
Stem Cell Res Ther ; 13(1): 124, 2022 03 24.
Article in English | MEDLINE | ID: covidwho-1759777

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread into more than 200 countries and infected approximately 203 million people globally. COVID-19 is associated with high mortality and morbidity in some patients, and this disease still does not have effective treatments with reproducibly appreciable outcomes. One of the leading complications associated with COVID-19 is acute respiratory distress syndrome (ARDS); this is an anti-viral host inflammatory response, and it is usually caused by a cytokine storm syndrome which may lead to multi-organ failure and death. Currently, COVID-19 patients are treated with approaches that mostly fall into two major categories: immunomodulators, which promote the body's fight against viruses efficiently, and antivirals, which slow or stop viruses from multiplying. These treatments include a variety of novel therapies that are currently being tested in clinical trials, including serum, IL-6 antibody, and remdesivir; however, the outcomes of these therapies are not consistently appreciable and remain a subject of debate. Mesenchymal stem/stromal cells (MSCs), the multipotent stem cells that have previously been used to treat viral infections and various respiratory diseases such as ARDS exhibit immunomodulatory properties and can ameliorate tissue damage. Given that SARS-CoV-2 targets the immune system and causes tissue damage, it is presumable that MSCs are being explored to treat COVID-19 patients. This review summarizes the potential mechanisms of action of MSC therapy, progress of MSC, and its related products in clinical trials for COVID-19 therapy based on the outcomes of these clinical studies.


Subject(s)
COVID-19 , Mesenchymal Stem Cells , Pneumonia , Respiratory Distress Syndrome , COVID-19/therapy , Humans , Mesenchymal Stem Cells/metabolism , SARS-CoV-2
3.
EBioMedicine ; 75: 103789, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1587925

ABSTRACT

BACKGROUND: The long-term consequences of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment for COVID-19 patients are yet to be reported. This study assessed the 1-year outcomes in patients with severe COVID-19, who were recruited in our previous UC-MSC clinical trial. METHODS: In this prospective, longitudinal, cohort study, 100 patients enrolled in our phase 2 trial were prospectively followed up at 3-month intervals for 1 year to evaluate the long-term safety and effectiveness of UC-MSC treatment. The primary endpoint was an altered proportion of whole-lung lesion volumes measured by high-resolution CT. Other imaging outcomes, 6 min walking distance (6-MWD), lung function, plasma biomarkers, and adverse events were also recorded and analyzed. This trial was registered with ClinicalTrials.gov (NCT04288102). FINDINGS: MSC administration improved in whole-lung lesion volume compared with the placebo with a difference of -10.8% (95% CI: -20.7%, -1.5%, p = 0.030) on day 10. MSC also reduced the proportion of solid component lesion volume compared with the placebo at each follow-up point. More interestingly, 17.9% (10/56) of patients in the MSC group had normal CT images at month 12, but none in the placebo group (p = 0.013). The incidence of symptoms was lower in the MSC group than in the placebo group at each follow-up time. Neutralizing antibodies were all positive, with a similar median inhibition rate (61.6% vs. 67.6%) in both groups at month 12. No difference in adverse events at the 1-year follow-up and tumor markers at month 12 were observed between the two groups. INTERPRETATION: UC-MSC administration achieves a long-term benefit in the recovery of lung lesions and symptoms in COVID-19 patients. FUNDING: The National Key R&D Program of China, the Innovation Groups of the National Natural Science Foundation of China, and the National Science and Technology Major Project.


Subject(s)
COVID-19/therapy , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Aged , Allografts , Double-Blind Method , Female , Follow-Up Studies , Humans , Male , Middle Aged , Patient Acuity
4.
Signal Transduct Target Ther ; 6(1): 58, 2021 02 10.
Article in English | MEDLINE | ID: covidwho-1078577

ABSTRACT

Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95% CI -29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.


Subject(s)
COVID-19/therapy , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , SARS-CoV-2 , Umbilical Cord , Aged , Allografts , COVID-19/mortality , COVID-19/physiopathology , Double-Blind Method , Female , Humans , Male , Middle Aged , Treatment Outcome
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