Safety and efficiency of stem cell therapy for COVID-19: a systematic review and meta-analysis

Abstract

Background With the COVID-19 pandemic continuing, various treatments have become widely practiced. Stem cells have a wide range of applications in the treatment of lung diseases and have therefore been experimentally used to treat patients with COVID-19, but whether the expanded use of stem cells is safe and reliable still lacks enough evidence. To address this issue, we systematically reviewed the safety and efficiency of stem cell therapy in COVID-19 cases. Methods We searched PubMed, Embase, Web of Science, The Cochrane Library, CNKI, WanFang, VIP and SinoMed up to January 18, 2022. The included studies were assessed using the Risk-of-bias tool 1.0 and MINORS instrument. The adverse events, mortality, length of hospital day and laboratory parameters were analyzed by meta-analysis. We adhered to PRISMA reporting guideline. Results We have included 17 studies meeting the inclusion data. There were no significant differences in AEs (OR = 0·39, 95% CI = 0·12 to 1·33, P = 0·13, I2 = 58%) and SAEs (OR = 0·21, 95% CI = 0·04 to 1·03, P = 0·05, I2 = 0%) between stem cell therapy group and control group. The analysis showed that stem cell treatment could significantly reduce the mortality rate(OR = 0·24, 95% CI = 0·13 to 0·45, P < 0·01, I2 = 0%), but was not able to cause changes in length of hospital stay or most laboratory parameters. Conclusions The present study shows that stem cell therapy for COVID-19 has a remarkable effect on efficiency without increasing risks of adverse events and length of hospital stay. It is potentially necessary to establish the criteria for COVID-19 for stem cell therapy.

Systematic review and meta-analysis of cell therapy for COVID-19: global clinical trial landscape, published safety/efficacy outcomes, cell product manufacturing and clinical delivery

“…We have included studies with no mortalities by assigning them RR=1.0. A third previous meta-analysis found OR=0.24 for twelve studies ( 99 ), although we caution that their meta-analysis mixed different cell types in the statistics.…”

Investigational Use of Mesenchymal Stem/Stromal Cells and Their Secretome as Add-On Therapy in Severe Respiratory Virus Infections: Challenges and Perspectives

“…The studies testing MSCs in COVID-19 differed greatly in terms of patient selection, MSC dosage, and infusion schedule (Tables 3 and 4). The outcome measures and follow-up periods also varied greatly (Tables 3, 6), precluding the possibility to perform meaningful meta-analyses, as previously recognized by the authors of recent systematic reviews not specifically focusing on the assessment of MSCs and MSCderived products as add-on therapy to the currently recommended standard of care [101][102][103][104]. Considering the safety outcomes, most reports did not contain complete and convincing information about the incidence of serious and non-serious adverse events and their relation to treatment (Table 5).…”

Análise compreensiva da resposta imune às infecções por ZIKV e SARS-CoV-2 em diferentes contextos patológicos

“…We have included studies with no mortalities by assigning them RR=1.0. A third previous meta-analysis found OR=0.24 for twelve studies 94 , although we caution that their meta-analysis mixed different cell types in the statistics.…”

“…For example, one study recruited convalescent patients to determine if MSC infusions would speed up the resolution of their lung lesions and consequently none of the patients died on either arm 49 . The previous meta-analyses have also noted that published studies with intravenous use of MSC for COVID-19 have very heterogeneous patient populations, in terms of the severity of their COVID-19 illness as well as the forms of concomitant therapies that they received [92][93][94]97 . Our statistical model has included more studies and more patients than previous metaanalyses of MSC efficacy for COVID-19 [92][93][94]97 .…”

“…We have summarized the RR and OR meta-analyses for different sub-groups and compared them with previous reports that presented RR / OR survival benefit of cell therapy for COVID-19 (Table 6) [92][93][94][95] . The first two previous meta-analyses in our table only used studies of IV MSC against controls, finding RR=0.54 for ten studies 92 and RR=0.50 for nine studies 93 , respectively.…”