Mesenchymal stem cell therapy in severe COVID-19: A retrospective study of short-term treatment efficacy and side effects

Chen, Xian; Shan, Yuheng; Wen, Yingyu; Sun, Jia; Du, Hong

doi:10.1016/j.jinf.2020.05.020

Cited by 58 publications

(75 citation statements)

References 7 publications

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“…MSC-based therapy protocols to treat COVID-19 have been directed mainly to patients with moderate and severe clinical presentations [9][10][11][12][13][14][15][16][17][18]. Few numbers of studies included critically ill patients with COVID-19 under invasive mechanical ventilation [24][25][26].…”

Section: Discussionmentioning

confidence: 99%

Intravenous Administration of Umbilical Cord Mesenchymal Stromal Cells in Advanced-stage Critical COVID-19: a Case Report

Silva

Pinheiro

Gobatto

et al. 2020

Preprint

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Background: Coronavirus disease 2019 (COVID-19) associated- severe acute respiratory distress syndrome (ARDS) patients may require prolonged mechanical ventilation, thus resulting in lung fibrosis and high fatality rates. Several therapies have been developed in patients with pneumonia requiring oxygen therapy as well as during the early course of invasive mechanical ventilation. Mesenchymal stromal cells (MSCs) may have a role in controlling the hyperinflammatory response seen in such cases and prevent aggravation or increase/accelerate recovery. While MSC-based therapies have been studied mostly in patients that did not require invasive ventilation or during the first hours of tracheal intubation, to date the potential of MSC therapy to treat advanced-stage of severe/critical COVID-19 cases has not been extensively studied. Methods: This is a case report of a 30-year-old male patient who presented progressive clinical deterioration of COVID-19 in ICU after 21-day admission and 14 days with invasive mechanical ventilation. The first symptom onset was 35 days before MSC therapy. The patient was treated with allogenic human umbilical cord-derived MSCs [5 x 107 (2 doses 2 days interval)].Results: No serious adverse events attributed to MSC administration were observed during and after the procedure. Oxygenation (PaO2/FiO2 ratio) and the need for vasoactive drugs improved. Chest CT scan imaging, which showed signs of bilateral and peripheral ground-glass, consolidation as well as fibrosis, improved significantly during the time course of the disease. Patient was discharged 13 days after cell therapy. Cytokine analysis demonstrated modulation of different mediators accompanied by modulation of different cell populations in peripheral blood, including a reduction in inflammatory monocytes, increased frequency of patrolling monocytes, CD4+ lymphocytes and type 2 classical dendritic cells (cDC2). Conclusion: This study described for the first time the effects of MSC therapy in a patient at late stage COVID-19 associated severe lung injury and fibrosis. Therefore, further clinical trials should be design assessing the efficacy of MSC therapy in ARDS patients undergoing prolonged mechanical ventilation due to COVID-19.

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Section: Discussionmentioning

confidence: 99%

Intravenous Administration of Umbilical Cord Mesenchymal Stromal Cells in Advanced-stage Critical COVID-19: a Case Report

Silva

Pinheiro

Gobatto

et al. 2020

Preprint

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“…The authors suggest an increase in peripheral blood regulatory T cells and dendritic cells in patients with more severe COVID-19, and reduction in circulating IL-10 and TNF-α levels, provide evidence of immunomodulation [133]. Chen et al, 2020, reported a retrospective review of 25 patients who received MSC therapy (between 1 and 3 infusions of 1 × 10 6 cells/kg) for COVID-19 pneumonia [134]. Data reported is extremely limited, with no detail of baseline physiological status or COVID-19 severity.…”

Section: Mscs In Covid-19 Trials and Reports (Summary Table 4)mentioning

confidence: 99%

Mesenchymal stromal cells for acute respiratory distress syndrome (ARDS), sepsis, and COVID-19 infection: optimizing the therapeutic potential

Gorman

Millar

O’Kane

2020

Expert Review of Respiratory Medicine

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Introduction: Mesenchymal stromal (stem) cell (MSC) therapies are emerging as a promising therapeutic intervention in patients with Acute Respiratory Distress Syndrome (ARDS) and sepsis due to their reparative, immunomodulatory, and antimicrobial properties. Areas covered: This review provides an overview of Mesenchymal stromal cells (MSCs) and their mechanisms of effect in ARDS and sepsis. The preclinical and clinical evidence to support MSC therapy in ARDS and sepsis is discussed. The potential for MSC therapy in COVID-19 ARDS is discussed with insights from respiratory viral models and early clinical reports of MSC therapy in COVID-19. Strategies to optimize the therapeutic potential of MSCs in ARDS and sepsis are considered including preconditioning, altered gene expression, and alternative cell-free MSC-derived products, such as extracellular vesicles and conditioned medium. Expert opinion: MSC products present considerable therapeutic promise for ARDS and sepsis. Preclinical investigations report significant benefits and early phase clinical studies have not highlighted safety concerns. Optimization of MSC function in preclinical models of ARDS and sepsis has enhanced their beneficial effects. MSC-derived products, as cell-free alternatives, may provide further advantages in this field. These strategies present opportunity for the clinical development of MSCs and MSC-derived products with enhanced therapeutic efficacy.

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“…In this context, MSC-based therapy would be plausible, because they are easily available and expanded from allogeneic tissue source, they may be previously cryopreserved and available “off the shelf” and easily intravenously infused. The remarkable immunomodulatory and regenerative abilities of MSCs may be effective for attenuating the cytokine storm and preventing progression to ARDS and multiple organ failure in severe COVID-19 patients [ 5 , 103 , 105 , 123 – 125 , 127 , 129 ]. In addition, intravenously infused MSCs become trapped in the lung.…”

Section: Future Directions Of Msc-based Therapies For Covid-19 and Otmentioning

confidence: 99%

Mesenchymal Stromal Cells in Viral Infections: Implications for COVID-19

Rocha

Oliveira

Noronha

et al. 2020

Stem Cell Rev and Rep

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Mesenchymal stromal cells (MSCs) constitute a heterogeneous population of stromal cells with immunomodulatory and regenerative properties that support their therapeutic use. MSCs isolated from many tissue sources replicate vigorously in vitro and maintain their main biological properties allowing their widespread clinical application. To date, most MSC-based preclinical and clinical trials targeted immune-mediated and inflammatory diseases. Nevertheless, MSCs have antiviral properties and have been used in the treatment of various viral infections in the last years. Here, we revised in detail the biological properties of MSCs and their preclinical and clinical applications in viral diseases, including the disease caused by the severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2) infection (COVID-19). Notably, rapidly increasing numbers of MSC-based therapies for COVID-19 have recently been reported. MSCs are theoretically capable of reducing inflammation and promote lung regeneration in severe COVID-19 patients. We critically discuss the rationale, advantages and disadvantages of MSC-based therapies for viral infections and also specifically for COVID-19 and point out some directions in this field. Finally, we argue that MSC-based therapy may be a promising therapeutic strategy for severe COVID-19 and other emergent respiratory tract viral infections, beyond the viral infection diseases in which MSCs have already been clinically applied.

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Mesenchymal stem cell therapy in severe COVID-19: A retrospective study of short-term treatment efficacy and side effects

Abstract: Comparing hospitalised, community and staff COVID-19 infection rates during the early phase of the evolving COVID-19 epidemicDear Editor,

Cited by 58 publications

References 7 publications

Intravenous Administration of Umbilical Cord Mesenchymal Stromal Cells in Advanced-stage Critical COVID-19: a Case Report

Intravenous Administration of Umbilical Cord Mesenchymal Stromal Cells in Advanced-stage Critical COVID-19: a Case Report

Mesenchymal stromal cells for acute respiratory distress syndrome (ARDS), sepsis, and COVID-19 infection: optimizing the therapeutic potential

Mesenchymal Stromal Cells in Viral Infections: Implications for COVID-19

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