Safety and Feasibility of Umbilical Cord Mesenchymal Stem Cells in Patients with COVID-19 Pneumonia: A Pilot Study

Feng, Ying; Huang, Jianying; Wu, Jianyuan; Xu, Yan; Chen, Bin; Jiang, Lijun; Xiang, Hui; Peng, Zhiyong; Wang, Xinghuan

doi:10.21203/rs.3.rs-62218/v1

Cited by 11 publications

(14 citation statements)

References 19 publications

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“…Safety was shown in other studies that also performed MSC-based interventions. They did not noticed any acute infusion-related issues, alergic reaction, delayed hypersensitivity or secondary infections in the patients either 39,45,47,48,54,76,77 .…”

Section: Discussionmentioning

confidence: 87%

“…Studies have shown that intravenous MSC infusion in patients with COVID-19 is safe and welltolerated. It prevents or reduces ARDS and other serious complications, decreases in ammatory cytokines and mortality, and in some cases improves pulmonary 39,[44][45][46][47][48][49][50][51][52][53][54][55][56] . Therapeutic interventions must decrease excess in ammation, thus preventing end-organ damage and long-term functional disability in moderate or severe COVID-19 patients.…”

Section: Introductionmentioning

confidence: 99%

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Safety and Long-term Improvement of Mesenchymal Stromal Cell Infusion in Critically COVID-19 Patients: A Randomized Clinical Trial.

Rebelatto

Senegaglia

Franck

et al. 2021

Preprint

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Background: COVID-19 is a multisystem disease that presents acute and persistent symptoms, the PostAcute Sequelae (PASC). Long-term symptoms may be due to consequences from organ or tissue injury caused by SARS-CoV-2, associated clotting or inflammatory processes during acute COVID-19. Various strategies are being chosen for by clinicians to prevent severe cases of COVID-19; however, a single treatment would not be efficient in treating such a complex disease. Mesenchymal stromal cells (MSCs) are known for their immunomodulatory properties and regeneration ability; therefore, they are a promising tool for treating disorders involving immune dysregulation and extensive tissue damage, as is the case with COVID-19. This study aimed to assess the safety and explore the long-term efficacy of three intravenous doses of UC-MSCs (umbilical cord-MSCs) as an adjunctive therapy in the recovery and postacute sequelae reduction caused by COVID-19. To our knowledge, this is the first report that presents the longest follow-up after MSC treatment in COVID-19 patients. Methods: This was a phase I/II, prospective, single-center, randomized, double-blind, placebo-controlled clinical trial. Seventeen patients diagnosed with COVID-19 who require intensive care surveillance and invasive mechanical ventilation – critically ill patients – were included. The patient infusion was three doses of 5x105 cells/kg UC-MSCs, with a dosing interval of 48 hours (n=11) or placebo (n=6). These evaluations consisted of a clinical assessment, viral load, laboratory testing, including blood count, serologic, biochemical, cell subpopulation, cytokines and CT scan. Results: The results revealed that in the UC-MSC group, there was a reduction in the levels of ferritin, IL-6 and MCP1-CCL2 on the fourteen day. In the second month, a decrease in the levels of reactive C-protein, D-dimer, and neutrophils and an increase in the numbers of TCD3, TCD4 and NK lymphocytes were observed. A decrease in lung extension was observed at the fourth month. The improvement in all these parameters was maintained until the end of patient follow-up. Conclusions: UC-MSCs infusion is safe and can play an important role as an adjunctive therapy, both in the early stages, preventing severe complications and in the chronic phase with postacute sequelae reduction in critically ill COVID-19 patients. Trial registration: Brazilian Registry of Clinical Trials (ReBEC), UTN code - U1111-1254-9819. Registered 31 October 2020 - Retrospectively registered, https://ensaiosclinicos.gov.br/rg/RBR-3fz9yr

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Safety and Long-term Improvement of Mesenchymal Stromal Cell Infusion in Critically COVID-19 Patients: A Randomized Clinical Trial.

Rebelatto

Senegaglia

Franck

et al. 2021

Preprint

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“…7 However, mesenchymal stem cells which was investigated extensively in recent years might be an eligible candidate. [8][9][10][11] In the entire course of his illness, the serum IL-6 (62 pg/mL), ferritin (1.21 g/L), and LDH (780 U/L) only had a slight elevation in the early period, there is no typical cytokine storm as that was seen in non-COVID-19 ARDS. The COVID-19 associated thrombosis has been noticed by many clinicians, 12,13 heparin was regularly used to prevent thrombosis even after the patient was weaned from ECMO.…”

Section: Discussionmentioning

confidence: 90%

Severe 2019 novel coronavirus pneumonia may cause lung bullae and bronchiectasis: A case report and concise literature review

et al. 2021

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Most of the critically ill novel coronavirus 2019 pneumonia (NCP) patients progress promptly, and soon match the ARDS diagnostic criteria. When mechanical ventilation and prone position cannot reverse the fatal hypoxia—extra-corporeal-membrane-oxygenation (ECMO) will be applied as a salvage treatment if available. Here, we report a novel coronavirus 2019 pneumonia (NCP) patient, a male, 67 years old, who was treated with ECMO for 30 days. In the midst, bronchoscopy was utilized to comprehend the airway lesions and clear secretions. And computed tomography (CT) scans were performed before and after the treatment of ECMO. In the recovering phase of his disease, the patient experienced multiple times pneumothorax on both sides. Some newly developed lung bullae in the subpleural area and modest bronchiectasis were found by the CT scan. The newly developed lung bullae was the probable cause of pneumothorax. Notably, in the whole process of his illness, the serum IL-6 only had a slight elevation in the early period, there is no typical cytokine storm as that was seen in non-COVID-19 ARDS. After 3-months meticulous treatment, the patient made a full recovery and now is discharged from our hospital. Though COVID-19 may not cause typical cytokine storm, the inflammation in lung may inflict severe damage to lung. Severe NCP may cause lung bullae and bronchiectasis, making the patients hard to be weaned from mechanical ventilation or ECMO.

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“…Of the 25 included studies, we included 3 RCTs, 37,44,45 5 comparative observational studies, [46][47][48][49][50] and 17 case-series/case reports. [51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67] The studies were conducted in seven countries, including Asia (n=16), Europe (n=6), North America (n=2), and South America (n=1).…”

Section: Resultsmentioning

confidence: 99%

Effectiveness and Safety of MSC Cell Therapies for Hospitalized Patients with COVID-19: A Systematic Review and Meta-analysis

Wang

Cook

et al. 2021

Preprint

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MSC (a.k.a. mesenchymal stem cell or medicinal signaling cell) cell therapies have shown promise in decreasing mortality in ARDS and suggest benefits in treatment of COVID-19 related ARDS. We performed a meta-analysis of published trials assessing the effectiveness and adverse events (AE) of MSC cell therapy in individuals hospitalized for COVID-19. Systematic searches were performed in multiple databases through April 8th, 2021. Reports in all languages including randomized clinical trials (RCTs), comparative observational studies, and case series/case reports were included. Random effects model was used to pool outcomes from RCTs and comparative observational studies. Outcome measures included all-cause mortality, serious adverse events (SAEs), AEs, pulmonary function, laboratory and imaging findings. A total of 413 patients were identified from 25 studies, which included 8 controlled trials (3 RCTs), 5 comparative observational studies, (n=300) and 17 case-series/case reports (n=113). The patients age was 60.5 years (mean), 33.7% were women. When compared with the control group, MSC cell therapy was associated with reduction in all-cause mortality (RR=0.31, 95% CI: 0.12 to 0.75, I2=0.0%; 3 RCTs and 5 comparative observational studies, 300 patients), reduction in SAEs (IRR=0.36, 95% CI: 0.14 to 0.90, I2=0.0%; 3 RCTs and 2 comparative studies, n=219), no significant difference in AE rate. A sub-group with pulmonary function studies suggested improvement in patients receiving MSC. These findings support the potential for MSC cell therapy to decrease all-cause mortality, reduce SAEs, and improve pulmonary function compared to conventional care. Large scale double-blinded, well-powered RCTs should be conducted to further explore these results.

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Safety and Feasibility of Umbilical Cord Mesenchymal Stem Cells in Patients with COVID-19 Pneumonia: A Pilot Study

Cited by 11 publications

References 19 publications

Safety and Long-term Improvement of Mesenchymal Stromal Cell Infusion in Critically COVID-19 Patients: A Randomized Clinical Trial.

Safety and Long-term Improvement of Mesenchymal Stromal Cell Infusion in Critically COVID-19 Patients: A Randomized Clinical Trial.

Severe 2019 novel coronavirus pneumonia may cause lung bullae and bronchiectasis: A case report and concise literature review

Effectiveness and Safety of MSC Cell Therapies for Hospitalized Patients with COVID-19: A Systematic Review and Meta-analysis

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