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Efficacy of MSC in Patients with Severe COVID-19: Analysis of the Literature and a Case Study
Patients with severe COVID-19 experience cytokine storm, an uncontrolled upregulation of pro-inflammatory cytokines, which if unresolved leads to acute respiratory distress syndrome (ARDS), organ damage, and death. Treatments with mesenchymal stromal cells (MSC) [Viswanathan S, Shi Y, Galipeau J, et...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9672850/ https://www.ncbi.nlm.nih.gov/pubmed/36181766 http://dx.doi.org/10.1093/stcltm/szac067 |
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author | Grumet, Martin Sherman, Jason Dorf, Barry S |
author_facet | Grumet, Martin Sherman, Jason Dorf, Barry S |
author_sort | Grumet, Martin |
collection | PubMed |
description | Patients with severe COVID-19 experience cytokine storm, an uncontrolled upregulation of pro-inflammatory cytokines, which if unresolved leads to acute respiratory distress syndrome (ARDS), organ damage, and death. Treatments with mesenchymal stromal cells (MSC) [Viswanathan S, Shi Y, Galipeau J, et al. Mesenchymal stem versus stromal cells: International Society for Cell & Gene Therapy Mesenchymal Stromal Cell committee position statement on nomenclature. Cytotherapy. 2019;21:1019-1024] appear to be effective in reducing morbidity and mortality. MSC respond to pro-inflammatory cytokines by releasing anti-inflammatory factors and mobilizing immune cells. We analyzed 82 COVID-19 clinical trials registered at ClinicalTrials.gov to determine MSC dosing, routes of administration, and outcome measures. Nearly all trials described the use of intravenous delivery with most doses ranging between 50 and 125 million MSC/treatment, which overlaps with a minimal effective dose range that we described previously. We also searched the literature to analyze clinical trial reports that used MSC to treat COVID-19. MSC were found to improve survival and oxygenation, increase discharge from intensive care units and hospitals, and reduce levels of pro-inflammatory markers. We report on a 91-year-old man with severe COVID-19 who responded rapidly to MSC treatment with transient reductions in several pro-inflammatory markers and delayed improvement in oxygenation. The results suggest that frequent monitoring of pro-inflammatory markers for severe COVID-19 will provide improved treatment guidelines by determining relationships between cytokine storms and ARDS. We propose that markers for cytokine storm are leading indicators for ARDS and that measurement of cytokines will indicate earlier treatment with MSC than is performed now for ARDS in severe COVID-19. |
format | Online Article Text |
id | pubmed-9672850 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-96728502022-11-21 Efficacy of MSC in Patients with Severe COVID-19: Analysis of the Literature and a Case Study Grumet, Martin Sherman, Jason Dorf, Barry S Stem Cells Transl Med Human Clinical Articles Patients with severe COVID-19 experience cytokine storm, an uncontrolled upregulation of pro-inflammatory cytokines, which if unresolved leads to acute respiratory distress syndrome (ARDS), organ damage, and death. Treatments with mesenchymal stromal cells (MSC) [Viswanathan S, Shi Y, Galipeau J, et al. Mesenchymal stem versus stromal cells: International Society for Cell & Gene Therapy Mesenchymal Stromal Cell committee position statement on nomenclature. Cytotherapy. 2019;21:1019-1024] appear to be effective in reducing morbidity and mortality. MSC respond to pro-inflammatory cytokines by releasing anti-inflammatory factors and mobilizing immune cells. We analyzed 82 COVID-19 clinical trials registered at ClinicalTrials.gov to determine MSC dosing, routes of administration, and outcome measures. Nearly all trials described the use of intravenous delivery with most doses ranging between 50 and 125 million MSC/treatment, which overlaps with a minimal effective dose range that we described previously. We also searched the literature to analyze clinical trial reports that used MSC to treat COVID-19. MSC were found to improve survival and oxygenation, increase discharge from intensive care units and hospitals, and reduce levels of pro-inflammatory markers. We report on a 91-year-old man with severe COVID-19 who responded rapidly to MSC treatment with transient reductions in several pro-inflammatory markers and delayed improvement in oxygenation. The results suggest that frequent monitoring of pro-inflammatory markers for severe COVID-19 will provide improved treatment guidelines by determining relationships between cytokine storms and ARDS. We propose that markers for cytokine storm are leading indicators for ARDS and that measurement of cytokines will indicate earlier treatment with MSC than is performed now for ARDS in severe COVID-19. Oxford University Press 2022-10-01 /pmc/articles/PMC9672850/ /pubmed/36181766 http://dx.doi.org/10.1093/stcltm/szac067 Text en © The Author(s) 2022. Published by Oxford University Press. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Human Clinical Articles Grumet, Martin Sherman, Jason Dorf, Barry S Efficacy of MSC in Patients with Severe COVID-19: Analysis of the Literature and a Case Study |
title | Efficacy of MSC in Patients with Severe COVID-19: Analysis of the Literature and a Case Study |
title_full | Efficacy of MSC in Patients with Severe COVID-19: Analysis of the Literature and a Case Study |
title_fullStr | Efficacy of MSC in Patients with Severe COVID-19: Analysis of the Literature and a Case Study |
title_full_unstemmed | Efficacy of MSC in Patients with Severe COVID-19: Analysis of the Literature and a Case Study |
title_short | Efficacy of MSC in Patients with Severe COVID-19: Analysis of the Literature and a Case Study |
title_sort | efficacy of msc in patients with severe covid-19: analysis of the literature and a case study |
topic | Human Clinical Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9672850/ https://www.ncbi.nlm.nih.gov/pubmed/36181766 http://dx.doi.org/10.1093/stcltm/szac067 |
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