PMID- 37128999 OWN - NLM STAT- MEDLINE DCOM- 20230503 LR - 20230513 IS - 1753-4666 (Electronic) IS - 1753-4658 (Print) IS - 1753-4658 (Linking) VI - 17 DP - 2023 Jan-Dec TI - Systematic review and meta-analysis of mesenchymal stromal/stem cells as strategical means for the treatment of COVID-19. PG - 17534666231158276 LID - 10.1177/17534666231158276 [doi] LID - 17534666231158276 AB - BACKGROUND: In coronavirus disease 2019 (COVID-19) patients, elevated levels of inflammatory cytokines from over stimulation of immune cells have become a concern due to the potential outburst of cytokine storm that damages the tissues and organs, especially the lungs. This leads to the manifestation of COVID-19 symptoms, such as pneumonia, acute respiratory distress syndrome (ARDS), multiple organ failure, and eventually death. Mesenchymal stromal/stem cells (MSCs) are currently one of hopeful approaches in treating COVID-19 considering its anti-inflammatory and immunomodulatory functions. On that account, the number of clinical trials concerning the use of MSCs for COVID-19 has been increasing. However, the number of systematic reviews and meta-analysis that specifically discuss its potential as treatment for the disease is still lacking. Therefore, this review will assess the safety and efficacy of MSC administration in COVID-19 patients. OBJECTIVES: To pool evidence on the safety and efficacy of MSCs in treating COVID-19 by observing MSC-related adverse effects as well as evaluating its effects in reducing inflammatory response and improving pulmonary function. DATA SOURCES AND METHODS: Following literature search across six databases and one trial register, full-text retrieval, and screening against eligibility criteria, only eight studies were included for data extraction. All eight studies evaluated the use of umbilical cord-derived mesenchymal stromal/stem cell (UC-MSC), infused intravenously. Of these eight studies, six studies were included in meta-analysis on the incidence of mortality, adverse events (AEs), and serious adverse events (SAEs), and the levels of C-reactive protein (CRP) and interleukin (IL)-6. Meta-analysis on pulmonary function was not performed due to insufficient data. RESULTS: MSC-treated group showed significantly lower risk of mortality than the control group (p = 0.03). No statistical significance was observed on the incidence of AEs (p = 0.78) and SAEs (p = 0.44), and the levels of CRP (p = 0.06) and IL-6 (p = 0.09). CONCLUSION: MSCs were safe for use, with lower risk of mortality and no association with AEs. Regarding efficacy, descriptive analysis showed indications of improvement on the inflammatory reaction, lung clearance, and oxygenation status despite the lack of statistical significance in meta-analysis of CRP and IL-6. Nevertheless, more studies are needed for affirmation. REGISTRATION: This systematic review and meta-analysis was registered on the PROSPERO database (no. CRD42022307730). FAU - Taufiq, Hannah AU - Taufiq H AD - Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia. FAU - Shaik Fakiruddin, Kamal AU - Shaik Fakiruddin K AD - Haematology Unit, Cancer Research Centre, Institute for Medical Research (IMR), National Institutes of Health (NIH), Ministry of Health Malaysia, Shah Alam, Selangor, Malaysia. FAU - Muzaffar, Umaiya AU - Muzaffar U AUID- ORCID: 0000-0002-6785-3388 AD - UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia. FAU - Lim, Moon Nian AU - Lim MN AD - Haematology Unit, Cancer Research Centre, Institute for Medical Research (IMR), National Institutes of Health (NIH), Ministry of Health Malaysia, Shah Alam, Selangor, Malaysia. FAU - Rusli, Syahnaz AU - Rusli S AD - Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia. FAU - Kamaluddin, Nor Rizan AU - Kamaluddin NR AD - Haematology Unit, Cancer Research Centre, Institute for Medical Research (IMR), National Institutes of Health (NIH), Ministry of Health Malaysia, Shah Alam, Selangor, Malaysia. FAU - Esa, Ezalia AU - Esa E AD - Haematology Unit, Cancer Research Centre, Institute for Medical Research (IMR), National Institutes of Health (NIH), Ministry of Health Malaysia, Shah Alam, Selangor, Malaysia. FAU - Abdullah, Syahril AU - Abdullah S AD - Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia. AD - UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Review PT - Systematic Review PL - England TA - Ther Adv Respir Dis JT - Therapeutic advances in respiratory disease JID - 101316317 RN - 0 (Interleukin-6) RN - 0 (Cytokines) SB - IM MH - Humans MH - *COVID-19 MH - SARS-CoV-2/metabolism MH - Interleukin-6/metabolism MH - *Mesenchymal Stem Cell Transplantation/adverse effects MH - Cytokines/metabolism MH - *Mesenchymal Stem Cells/metabolism PMC - PMC10140776 OTO - NOTNLM OT - COVID-19 OT - SARS-CoV-2 OT - mesenchymal stromal/stem cells COIS- The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2023/05/02 06:42 MHDA- 2023/05/03 06:42 PMCR- 2023/04/27 CRDT- 2023/05/02 05:43 PHST- 2023/05/03 06:42 [medline] PHST- 2023/05/02 06:42 [pubmed] PHST- 2023/05/02 05:43 [entrez] PHST- 2023/04/27 00:00 [pmc-release] AID - 10.1177_17534666231158276 [pii] AID - 10.1177/17534666231158276 [doi] PST - ppublish SO - Ther Adv Respir Dis. 2023 Jan-Dec;17:17534666231158276. doi: 10.1177/17534666231158276.