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.

Autor:	Couto PS; Department of Biochemical Engineering, Advanced Centre for Biochemical Engineering, University College London, London, United Kingdom.; CellTrials.org and Parent's Guide to Cord Blood Foundation, a non-profit organization headquartered in Brookeville, Brookeville, MD, United States., Al-Arawe N; Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health (BIH), Berlin, Germany.; Vascular Surgery Clinic, Charité Universitätsmedizin Berlin, Berlin, Germany., Filgueiras IS; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil., Fonseca DLM; Interunit Postgraduate Program on Bioinformatics, Institute of Mathematics and Statistics (IME), University of São Paulo (USP), São Paulo, SP, Brazil., Hinterseher I; Vascular Surgery Clinic, Charité Universitätsmedizin Berlin, Berlin, Germany.; Department of Vascular Surgery, Universitätsklinikum Ruppin-Brandenburg, Medizinische Hochschule Brandenburg Theodor Fontane, Neuruppin, Germany.; Fakultät der Gesundheitswissenschaften Brandenburg, Gemeinsame Fakultät der Universität Potsdam, der Medizinischen Hochschule Brandenburg Theodor Fontane, und der Brandenburg Technischen Universität (BTU) Cottbus-Senftenberg, Potsdam, Germany., Catar RA; Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health (BIH), Berlin, Germany., Chinnadurai R; Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA, United States., Bersenev A; Advanced Cell Therapy (ACT) Laboratory, Yale School of Medicine, New Haven, CT, United States., Cabral-Marques O; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.; Interunit Postgraduate Program on Bioinformatics, Institute of Mathematics and Statistics (IME), University of São Paulo (USP), São Paulo, SP, Brazil.; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.; Department of Pharmacy and Postgraduate Program of Health and Science, Federal University of Rio Grande do Norte, Natal, Brazil.; Department of Medicine, Division of Molecular Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.; Laboratory of Medical Investigation 29, University of São Paulo School of Medicine, São Paulo, Brazil., Moll G; Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health (BIH), Berlin, Germany.; Berlin Institute of Health (BIH) Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Berlin, Germany., Verter F; CellTrials.org and Parent's Guide to Cord Blood Foundation, a non-profit organization headquartered in Brookeville, Brookeville, MD, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Jun 21; Vol. 14, pp. 1200180. Date of Electronic Publication: 2023 Jun 21 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1200180
Abstrakt:	During the pandemic of severe respiratory distress syndrome coronavirus 2 (SARS-CoV2), many novel therapeutic modalities to treat Coronavirus 2019 induced disease (COVID-19) were explored. This study summarizes 195 clinical trials of advanced cell therapies targeting COVID-19 that were registered over the two years between January 2020 to December 2021. In addition, this work also analyzed the cell manufacturing and clinical delivery experience of 26 trials that published their outcomes by July 2022. Our demographic analysis found the highest number of cell therapy trials for COVID-19 was in United States, China, and Iran (N=53, 43, and 19, respectively), with the highest number per capita in Israel, Spain, Iran, Australia, and Sweden (N=0.641, 0.232, 0,223, 0.194, and 0.192 trials per million inhabitants). The leading cell types were multipotent mesenchymal stromal/stem cells (MSCs), natural killer (NK) cells, and mononuclear cells (MNCs), accounting for 72%, 9%, and 6% of the studies, respectively. There were 24 published clinical trials that reported on infusions of MSCs. A pooled analysis of these MSC studies found that MSCs provide a relative risk reduction for all-cause COVID-19 mortality of RR=0.63 (95% CI 0.46 to 0.85). This result corroborates previously published smaller meta-analyses, which suggested that MSC therapy demonstrated a clinical benefit for COVID-19 patients. The sources of the MSCs used in these studies and their manufacturing and clinical delivery methods were remarkably heterogeneous, with some predominance of perinatal tissue-derived products. Our results highlight the important role that cell therapy products may play as an adjunct therapy in the management of COVID-19 and its related complications, as well as the importance of controlling key manufacturing parameters to ensure comparability between studies. Thus, we support ongoing calls for a global registry of clinical studies with MSC products that could better link cell product manufacturing and delivery methods to clinical outcomes. Although advanced cell therapies may provide an important adjunct treatment for patients affected by COVID-19 in the near future, preventing pathology through vaccination still remains the best protection to date. We conducted a systematic review and meta-analysis of advanced cell therapy clinical trials as potential novel treatment for COVID-19 (resulting from SARS-CoV-2 coronavirus infection), including analysis of the global clinical trial landscape, published safety/efficacy outcomes (RR/OR), and details on cell product manufacturing and clinical delivery. This study had a 2-year observation interval from start of January 2020 to end of December 2021, including a follow-up period until end of July to identify published outcomes, which covers the most vivid period of clinical trial activity, and is also the longest observation period studied until today. In total, we identified 195 registered advanced cell therapy studies for COVID-19, employing 204 individual cell products. Leading registered trial activity was attributed to the USA, China, and Iran. Through the end of July 2022, 26 clinical trials were published, with 24 out of 26 articles employing intravenous infusions (IV) of mesenchymal stromal/stem cell (MSC) products. Most of the published trials were attributed to China and Iran. The cumulative results from the 24 published studies employing infusions of MSCs indicated an improved survival (RR=0.63 with 95% Confidence Interval 0.46 to 0.85). Our study is the most comprehensive systematic review and meta-analysis on cell therapy trials for COVID-19 conducted to date, clearly identifying the USA, China, and Iran as leading advanced cell therapy trial countries for COVID-19, with further strong contributions from Israel, Spain, Australia and Sweden. Although advanced cell therapies may provide an important adjunct treatment for patients affected by COVID-19 in the future, preventing pathology through vaccination remains the best protection. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Couto, Al-Arawe, Filgueiras, Fonseca, Hinterseher, Catar, Chinnadurai, Bersenev, Cabral-Marques, Moll and Verter.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu