Safety and long-term improvement of mesenchymal stromal cell infusion in critically COVID-19 patients: a randomized clinical trial
Abstract 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. Vario...
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| Format: | Article |
| Language: | English |
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BMC
2022-03-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-022-02796-1 |
| _version_ | 1811331907908009984 |
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| author | Carmen Lúcia Kuniyoshi Rebelatto Alexandra Cristina Senegaglia Claudio Luciano Franck Debora Regina Daga Patrícia Shigunov Marco Augusto Stimamiglio Daniela Boscaro Marsaro Bruna Schaidt Andressa Micosky Ana Paula de Azambuja Cleverson Alex Leitão Ricardo Rasmussen Petterle Valderez Ravaglio Jamur Isadora May Vaz Antônio Paulo Mallmann Hipólito Carraro Junior Eduardo Ditzel Paulo Roberto Slud Brofman Alejandro Correa |
| author_facet | Carmen Lúcia Kuniyoshi Rebelatto Alexandra Cristina Senegaglia Claudio Luciano Franck Debora Regina Daga Patrícia Shigunov Marco Augusto Stimamiglio Daniela Boscaro Marsaro Bruna Schaidt Andressa Micosky Ana Paula de Azambuja Cleverson Alex Leitão Ricardo Rasmussen Petterle Valderez Ravaglio Jamur Isadora May Vaz Antônio Paulo Mallmann Hipólito Carraro Junior Eduardo Ditzel Paulo Roberto Slud Brofman Alejandro Correa |
| author_sort | Carmen Lúcia Kuniyoshi Rebelatto |
| collection | DOAJ |
| description | Abstract 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 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 one of the few reports 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 5 × 105 cells/kg UC-MSCs, with a dosing interval of 48 h (n = 11) or placebo (n = 6). The 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 extension of lung damage 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 |
| first_indexed | 2024-04-13T16:27:53Z |
| format | Article |
| id | doaj.art-96fa540172f94d59bb19aa78e417c330 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-13T16:27:53Z |
| publishDate | 2022-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-96fa540172f94d59bb19aa78e417c3302022-12-22T02:39:41ZengBMCStem Cell Research & Therapy1757-65122022-03-0113112210.1186/s13287-022-02796-1Safety and long-term improvement of mesenchymal stromal cell infusion in critically COVID-19 patients: a randomized clinical trialCarmen Lúcia Kuniyoshi Rebelatto0Alexandra Cristina Senegaglia1Claudio Luciano Franck2Debora Regina Daga3Patrícia Shigunov4Marco Augusto Stimamiglio5Daniela Boscaro Marsaro6Bruna Schaidt7Andressa Micosky8Ana Paula de Azambuja9Cleverson Alex Leitão10Ricardo Rasmussen Petterle11Valderez Ravaglio Jamur12Isadora May Vaz13Antônio Paulo Mallmann14Hipólito Carraro Junior15Eduardo Ditzel16Paulo Roberto Slud Brofman17Alejandro Correa18Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica Do ParanáCore for Cell Technology, School of Medicine, Pontifícia Universidade Católica Do ParanáComplexo Hospital de Clínicas, Universidade Federal do ParanáCore for Cell Technology, School of Medicine, Pontifícia Universidade Católica Do ParanáNational Institute of Science and Technology for Regenerative Medicine, INCT-REGENERANational Institute of Science and Technology for Regenerative Medicine, INCT-REGENERACore for Cell Technology, School of Medicine, Pontifícia Universidade Católica Do ParanáCore for Cell Technology, School of Medicine, Pontifícia Universidade Católica Do ParanáCore for Cell Technology, School of Medicine, Pontifícia Universidade Católica Do ParanáComplexo Hospital de Clínicas, Universidade Federal do ParanáComplexo Hospital de Clínicas, Universidade Federal do ParanáStatistics, Health Sciences Sector, Federal University of ParanáCore for Cell Technology, School of Medicine, Pontifícia Universidade Católica Do ParanáCore for Cell Technology, School of Medicine, Pontifícia Universidade Católica Do ParanáHospital e Maternidade BrígidaComplexo Hospital de Clínicas, Universidade Federal do ParanáHospital Nossa Senhora do PilarCore for Cell Technology, School of Medicine, Pontifícia Universidade Católica Do ParanáNational Institute of Science and Technology for Regenerative Medicine, INCT-REGENERAAbstract 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 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 one of the few reports 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 5 × 105 cells/kg UC-MSCs, with a dosing interval of 48 h (n = 11) or placebo (n = 6). The 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 extension of lung damage 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-3fz9yrhttps://doi.org/10.1186/s13287-022-02796-1COVID-19Mesenchymal stromal cellsPostacute sequelaeCell therapy |
| spellingShingle | Carmen Lúcia Kuniyoshi Rebelatto Alexandra Cristina Senegaglia Claudio Luciano Franck Debora Regina Daga Patrícia Shigunov Marco Augusto Stimamiglio Daniela Boscaro Marsaro Bruna Schaidt Andressa Micosky Ana Paula de Azambuja Cleverson Alex Leitão Ricardo Rasmussen Petterle Valderez Ravaglio Jamur Isadora May Vaz Antônio Paulo Mallmann Hipólito Carraro Junior Eduardo Ditzel Paulo Roberto Slud Brofman Alejandro Correa Safety and long-term improvement of mesenchymal stromal cell infusion in critically COVID-19 patients: a randomized clinical trial Stem Cell Research & Therapy COVID-19 Mesenchymal stromal cells Postacute sequelae Cell therapy |
| title | Safety and long-term improvement of mesenchymal stromal cell infusion in critically COVID-19 patients: a randomized clinical trial |
| title_full | Safety and long-term improvement of mesenchymal stromal cell infusion in critically COVID-19 patients: a randomized clinical trial |
| title_fullStr | Safety and long-term improvement of mesenchymal stromal cell infusion in critically COVID-19 patients: a randomized clinical trial |
| title_full_unstemmed | Safety and long-term improvement of mesenchymal stromal cell infusion in critically COVID-19 patients: a randomized clinical trial |
| title_short | Safety and long-term improvement of mesenchymal stromal cell infusion in critically COVID-19 patients: a randomized clinical trial |
| title_sort | safety and long term improvement of mesenchymal stromal cell infusion in critically covid 19 patients a randomized clinical trial |
| topic | COVID-19 Mesenchymal stromal cells Postacute sequelae Cell therapy |
| url | https://doi.org/10.1186/s13287-022-02796-1 |
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