Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trialResearch in context
Summary: Background: Long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in our previous randomized...
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| Language: | English |
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Elsevier
2023-06-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396423001652 |
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| author | Tian-Tian Li Bo Zhang Hui Fang Ming Shi Wei-Qi Yao Yuanyuan Li Chao Zhang Jinwen Song Lei Huang Zhe Xu Xin Yuan Jun-Liang Fu Cheng Zhen Yu Zhang Ze-Rui Wang Zi-Ying Zhang Meng-Qi Yuan Tengyun Dong Ruidan Bai Lulu Zhao Jianming Cai Jinghui Dong Jianzeng Zhang Wei-Fen Xie Yonggang Li Lei Shi Fu-Sheng Wang |
| author_facet | Tian-Tian Li Bo Zhang Hui Fang Ming Shi Wei-Qi Yao Yuanyuan Li Chao Zhang Jinwen Song Lei Huang Zhe Xu Xin Yuan Jun-Liang Fu Cheng Zhen Yu Zhang Ze-Rui Wang Zi-Ying Zhang Meng-Qi Yuan Tengyun Dong Ruidan Bai Lulu Zhao Jianming Cai Jinghui Dong Jianzeng Zhang Wei-Fen Xie Yonggang Li Lei Shi Fu-Sheng Wang |
| author_sort | Tian-Tian Li |
| collection | DOAJ |
| description | Summary: Background: Long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in our previous randomized, double-blind, placebo-controlled clinical trial (NCT 04288102). Methods: A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4 × 107 cells per infusion) or a placebo (n = 35) combined with standard of care on days 0, 3, and 6. Patients were subsequently evaluated 18 and 24 months after treatment to evaluate the long-term safety and efficacy of the MSC treatment. Outcomes measured included: 6-min walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire (SF-36), COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, tumor markers, and MSC-related adverse events (AEs). Findings: Two years after treatment, a marginally smaller proportion of patients had a 6-MWD below the lower limit of the normal range in the MSC group than in the placebo group (OR = 0.19, 95% CI: 0.04–0.80, Fisher's exact test, p = 0.015). At month 18, the general health score from the SF-36 was higher in the MSC group than in the placebo group (50.00 vs. 35.00, 95% CI: 0.00–20.00, Wilcoxon rank sum test, p = 0.018). Total severity score of lung imaging and the titer of neutralizing antibodies were similar between the two groups at months 18 and 24. There was no difference in AEs or tumor markers at the 2-year follow-up between the two groups. Interpretation: Long-term safety was observed for the COVID-19 patients who received MSC treatment. However, efficacy of MSC treatment was not significantly sustained through the end of the 2-year follow-up period. Funding: The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900, 2022YFC2304401), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202216) and the Fund of National Clinical Center for Infectious Diseases, PLA General Hospital (NCRC-ID202105,413FZT6). |
| first_indexed | 2024-04-09T14:11:47Z |
| format | Article |
| id | doaj.art-3b283893b18e47c5a4cb7e255aabc5e4 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-09T14:11:47Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-3b283893b18e47c5a4cb7e255aabc5e42023-05-06T04:38:26ZengElsevierEBioMedicine2352-39642023-06-0192104600Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trialResearch in contextTian-Tian Li0Bo Zhang1Hui Fang2Ming Shi3Wei-Qi Yao4Yuanyuan Li5Chao Zhang6Jinwen Song7Lei Huang8Zhe Xu9Xin Yuan10Jun-Liang Fu11Cheng Zhen12Yu Zhang13Ze-Rui Wang14Zi-Ying Zhang15Meng-Qi Yuan16Tengyun Dong17Ruidan Bai18Lulu Zhao19Jianming Cai20Jinghui Dong21Jianzeng Zhang22Wei-Fen Xie23Yonggang Li24Lei Shi25Fu-Sheng Wang26The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001, Hefei, China; Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, 100039, Beijing, ChinaDepartment of Infectious Disease, General Hospital of Central Theater Command, Wuhan, ChinaWuhan Optics Valley Zhongyuan Pharmaceutical Co., Ltd., 430030, Hubei, PR ChinaDepartment of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, 100039, Beijing, ChinaWuhan Optics Valley Zhongyuan Pharmaceutical Co., Ltd., 430030, Hubei, PR China; Department of Biology and Medicine, Hubei University of Technology, 430030, Wuhan, Hubei, PR China; VCANBIO Cell & Gene Engineering Corp., Ltd., Tianjin, ChinaDepartment of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, 100039, Beijing, ChinaDepartment of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, 100039, Beijing, ChinaDepartment of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, 100039, Beijing, ChinaDepartment of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, 100039, Beijing, ChinaDepartment of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, 100039, Beijing, ChinaDepartment of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, 100039, Beijing, ChinaDepartment of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, 100039, Beijing, ChinaDepartment of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, 100039, Beijing, ChinaWuhan Optics Valley Zhongyuan Pharmaceutical Co., Ltd., 430030, Hubei, PR China; VCANBIO Cell & Gene Engineering Corp., Ltd., Tianjin, ChinaDepartment of Gastroenterology, First Medical Center of Chinese PLA General Hospital, 100853, Beijing, China; Chinese PLA Medical School, 100853, Beijing, ChinaDepartment of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, 100039, Beijing, China; Chinese PLA Medical School, 100853, Beijing, ChinaDepartment of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, 100039, Beijing, China; Chinese PLA Medical School, 100853, Beijing, ChinaWuhan Optics Valley Vcanbio Cell & Gene Technology Co., Ltd, 430030, Hubei, PR ChinaWuhan Optics Valley Zhongyuan Pharmaceutical Co., Ltd., 430030, Hubei, PR ChinaWuhan Optics Valley Vcanbio Cell & Gene Technology Co., Ltd, 430030, Hubei, PR ChinaDepartment of Radiology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Radiology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Radiology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Gastroenterology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai, 200003, ChinaDepartment of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, 100039, Beijing, ChinaDepartment of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, 100039, Beijing, China; Chinese PLA Medical School, 100853, Beijing, China; Corresponding author. Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, No.100 Western 4th Ring Road, Beijing, 100039, China.The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001, Hefei, China; Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, 100039, Beijing, China; Chinese PLA Medical School, 100853, Beijing, China; Corresponding author. Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, No.100 Western 4th Ring Road, Beijing, 100039, China.Summary: Background: Long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in our previous randomized, double-blind, placebo-controlled clinical trial (NCT 04288102). Methods: A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4 × 107 cells per infusion) or a placebo (n = 35) combined with standard of care on days 0, 3, and 6. Patients were subsequently evaluated 18 and 24 months after treatment to evaluate the long-term safety and efficacy of the MSC treatment. Outcomes measured included: 6-min walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire (SF-36), COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, tumor markers, and MSC-related adverse events (AEs). Findings: Two years after treatment, a marginally smaller proportion of patients had a 6-MWD below the lower limit of the normal range in the MSC group than in the placebo group (OR = 0.19, 95% CI: 0.04–0.80, Fisher's exact test, p = 0.015). At month 18, the general health score from the SF-36 was higher in the MSC group than in the placebo group (50.00 vs. 35.00, 95% CI: 0.00–20.00, Wilcoxon rank sum test, p = 0.018). Total severity score of lung imaging and the titer of neutralizing antibodies were similar between the two groups at months 18 and 24. There was no difference in AEs or tumor markers at the 2-year follow-up between the two groups. Interpretation: Long-term safety was observed for the COVID-19 patients who received MSC treatment. However, efficacy of MSC treatment was not significantly sustained through the end of the 2-year follow-up period. Funding: The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900, 2022YFC2304401), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202216) and the Fund of National Clinical Center for Infectious Diseases, PLA General Hospital (NCRC-ID202105,413FZT6).http://www.sciencedirect.com/science/article/pii/S2352396423001652COVID-19Mesenchymal stem cell2-year follow-up |
| spellingShingle | Tian-Tian Li Bo Zhang Hui Fang Ming Shi Wei-Qi Yao Yuanyuan Li Chao Zhang Jinwen Song Lei Huang Zhe Xu Xin Yuan Jun-Liang Fu Cheng Zhen Yu Zhang Ze-Rui Wang Zi-Ying Zhang Meng-Qi Yuan Tengyun Dong Ruidan Bai Lulu Zhao Jianming Cai Jinghui Dong Jianzeng Zhang Wei-Fen Xie Yonggang Li Lei Shi Fu-Sheng Wang Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trialResearch in context EBioMedicine COVID-19 Mesenchymal stem cell 2-year follow-up |
| title | Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trialResearch in context |
| title_full | Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trialResearch in context |
| title_fullStr | Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trialResearch in context |
| title_full_unstemmed | Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trialResearch in context |
| title_short | Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trialResearch in context |
| title_sort | human mesenchymal stem cell therapy in severe covid 19 patients 2 year follow up results of a randomized double blind placebo controlled trialresearch in context |
| topic | COVID-19 Mesenchymal stem cell 2-year follow-up |
| url | http://www.sciencedirect.com/science/article/pii/S2352396423001652 |
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