Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration in COVID-19 (REALIST-COVID-19): A structured summary of a study protocol for a randomised, controlled trial

Gorman, Ellen; Shankar-Hari, Manu; Hopkins, Phil; Tunnicliffe, William; Perkins, Gavin D; Silversides, Jonathan A.; McGuigan, Peter; Jackson, Colette E.; Boyle, Roisin; McFerran, Jamie; McDowell, Clíona; Campbell, Christina; McFarland, Margaret; Smythe, Jon; Thompson, Jacqui; Williams, Barry; Curley, Gerard F.; Laffey, John G.; Clarke, Mike; O’Kane, Cecilia; McAuley, Daniel F.

doi:10.1186/s13063-020-04416-w

Cited by 27 publications

(22 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the end, producing the MSC exos is no more complex then producing the MSC, but in comparison, when available, have the advantage of an ‘off the shelf’ reagent. Certainly, use of the highest quality MSC product exosomes to avoid possible increased risk of coagulopathy (Moll et al., 2020), in matched, randomized, controlled trials should be the rule (Gorman et al., 2020).…”

Section: Covid 19 Therapy With Mesenchymal Stromal Cellsmentioning

confidence: 99%

COVID‐19 therapy with mesenchymal stromal cells (MSC) and convalescent plasma must consider exosome involvement: Do the exosomes in convalescent plasma antagonize the weak immune antibodies?

Askenase

2020

J of Extracellular Vesicle

View full text Add to dashboard Cite

Exosome extracellular vesicles as biologic therapy for COVID‐19 are discussed for two areas. The first involves the growing use of mesenchymal stromal cells (MSCs) for the profound clinical cytokine storm and severe pneumonia in COVID‐19 patients. Instead, it is recommended to treat alternatively with their MSC‐released exosomes. This is because many reports in the literature and our data have shown that the release of exosomes from the in vivo administered MSC is actually responsible for their beneficial effects. Further, the exosomes are superior, simpler and clinically more convenient compared to their parental MSC. Additionally, in the context of COVID‐19, the known tendency of MSC to intravascularly aggregate causing lung dysfunction might synergize with the pneumonia aspects, and the tendency of MSC peripheral vascular micro aggregates might synergize with the vascular clots of the COVID‐19 disease process, causing significant central or peripheral vascular insufficiency. The second exosome therapeutic area for severe COVID‐19 involves use of convalescent plasma for its content of acquired immune antibodies that must consider the role in this therapy of contained nearly trillions of exosomes. Many of these derive from activated immune modulating cells and likely can function to transfer miRNAs that acting epigenetically to also influence the convalescent plasma recipient response to the virus. There is sufficient evidence, like recovery of patients with antibody deficiencies, to postulate that the antibodies actually have little effect and that immune resistance is principally due to T cell mechanisms. Further, COVID‐19 convalescent plasma has remarkably weak beneficial effects if compared to what was expected from many prior studies. This may be due to the dysfunctional immune response to the infection and resulting weak Ab that may be impaired further by antagonistic exosomes in the convalescent plasma. At the least, pre selection of plasma for the best antibodies and relevant exosomes would produce the most optimum therapy for very severely affected COVID‐19 patients.

show abstract

Section: Covid 19 Therapy With Mesenchymal Stromal Cellsmentioning

confidence: 99%

COVID‐19 therapy with mesenchymal stromal cells (MSC) and convalescent plasma must consider exosome involvement: Do the exosomes in convalescent plasma antagonize the weak immune antibodies?

Askenase

2020

J of Extracellular Vesicle

View full text Add to dashboard Cite

show abstract

“…Furthermore, 14 patients (31.1%) required renal replacement therapy during ICU admission. 14 patients were enrolled in clinical trials(21,22). Other than low dose Hydrocortisone for septic shock, no patients received immune modulator or antiviral drugs outside the context of a clinical trial.…”

mentioning

confidence: 99%

Clinical characteristics and post-intensive care outcomes of COVID-19 pneumonia.

Cody¹,

Lakey²,

McMahon³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: COVID-19 can result in a severe viral pneumonia, with high reported mortality rates in patients requiring mechanical ventilation. There is controversy as to whether established therapeutic approaches to acute respiratory distress syndrome are optimal in this condition, and numerous novel therapies have been used, often outside the context of randomised trials. In addition, longer term quality of life outcomes associated with COVID-19 are as yet unknown. The aim of this case series is to describe demographic, physiological and outcome data of patients with COVID-19 admitted to our intensive care units who were treated according to evidence-based guidelines for acute respiratory distress syndrome.Methods: We retrospectively reviewed the records of all patients admitted to intensive care units in our institution with COVID-19 between March and June, 2020. Physiological and laboratory data were recorded at baseline and daily until intensive care discharge or death. Quality of life was assessed at a virtual post-intensive care follow-up clinic around 10 weeks after ICU discharge.Results: 45 patients with COVID-19 were included, 37 (82.2%) of whom were male, with a mean age of 55 years. 42 (93.3%) of this cohort met criteria for acute respiratory distress syndrome at time of admission. Clinical management was consistent with evidence based institutional guidelines introduced for acute respiratory distress syndrome. Median length of intensive care stay was 14 days. The intensive care mortality rate was 8.9%. Functional and psychological morbidity post intensive care was significant: 45.2% of respondents had at least moderate impairment of mobility and 35.5% described at least moderate symptoms of anxiety or depression at the time of follow up.Conclusions : This case series demonstrates low mortality in a cohort of patients treated according to an established evidence-based approach for acute respiratory distress syndrome. However, COVID-19 survivors have a marked functional and psychological morbidity impacting quality of life following ICU admission. The therapeutic goal in the future will be to achieve similar survival outcomes while minimizing the significant morbidity associated with COVID-19 related critical care admission.

show abstract

“…Complicatedly, extensive studies reported the converse views that MSCs displayed the function of inhibiting cell activation of immune system [22]. Thirdly, according to a recent clinical trial [23], the evaluation of efficacy outcome lacked several indexes, such as oxygenation index and Sequential Organ Failure Assessment score. Overall, with incomplete data in our case, including cytokines, immune cells and efficacy indexes, it is difficult to precisely evaluate the exact effect of the UCB-MSCs treatment.…”

Section: Discussionmentioning

confidence: 99%

Umbilical cord blood-derived mesenchymal stem cells in treating a critically ill COVID-19 patient

Tao

Nie

et al. 2020

J Infect Dev Ctries

View full text Add to dashboard Cite

Introduction: The coronavirus disease 2019 (COVID-19) pandemic is spreading rapidly. Critically ill cases of COVID-19 can rapidly progress to acute respiratory distress syndrome and multiple organ failures. However, no effective drugs have been available till now, leading to more than 300,000 deaths up to 29 April 2020. Here, we present a critically ill case utilizing umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs). Case presentation: A 72-year-old man was admitted, with the diagnosis of COVID-19, ARDS, type-2 diabetes, diabetic nephropathy, renal insufficiency, and hypertension. His clinical condition continually developed to be life-threatening even receiving various treatment options including antiviral therapy and extracorporeal membrane oxygenation. Between 28 February and 8 March 2020, the patient was given 5-time intravenous infusions of UCB-MSCs. His hematological and biochemical indexes, including lymphocytes and renal function improved. Pulmonary static compliance increased significantly and PaO2/FiO2 ratio maintained stable. On March 10, he received lung transplantation. Conclusions: Our current findings suggested that UCB-MSCs therapy may show some positive effect in treating critical COVID-19 to some extent, for its delaying deterioration of the disease and efficacy in respiratory and renal function, though limited.

show abstract

Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration in COVID-19 (REALIST-COVID-19): A structured summary of a study protocol for a randomised, controlled trial

Cited by 27 publications

References 0 publications

COVID‐19 therapy with mesenchymal stromal cells (MSC) and convalescent plasma must consider exosome involvement: Do the exosomes in convalescent plasma antagonize the weak immune antibodies?

COVID‐19 therapy with mesenchymal stromal cells (MSC) and convalescent plasma must consider exosome involvement: Do the exosomes in convalescent plasma antagonize the weak immune antibodies?

Clinical characteristics and post-intensive care outcomes of COVID-19 pneumonia.

Umbilical cord blood-derived mesenchymal stem cells in treating a critically ill COVID-19 patient

Contact Info

Product

Resources

About