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Authors: Shu, et al.

Link to paper: https://www.researchsquare.com/article/rs-23696/v1

Journal/ Pre-Print: Stem Cell Research and Therapy

Tags: Treatment, Stem cell

Research Highlights

1. Patients with severe COVID-19 infused with hUC-MSCs have a lower mortality rate compared to control.

2. Increased rate of resolution of inflammation as measured by IL-6 and CRP in patients infused with hUC-MSCs.

Summary

A small cohort study, the authors lay out that COVID-19 patients treated with hUC-MSCs are less likely to die, and are more likely to exhibit a greater degree of symptomatic relief compared to control. However, patient inclusion/exclusion criteria are poorly defined, and parameters of symptomatic improvement are limited to CRP, IL-6, total lymphocyte count, and oxygenation index. Notably, there were significant reductions in IL-6 and CRP and significant increases in lymphocyte count and oxygenation index in the hUC-MSC cohort compared to control. Aside from ‘antiviral drugs’ and ‘systemic glucocorticoids’ it is unclear as to whether patient management was constant across the control and intervention cohorts. There is no mechanistic insight as to how hUC-MSCs may result in greater symptomatic relief aside from reduced lung inflammation.

Impact for SARS-CoV2/COVID19 research efforts

Treatment of SARS-CoV2/COVID19 positive individuals

Tentative evidence that the infusion of hUC-MSCs in patients positive for COVID-19 can reduce mortality rate and increase the rate of clinical improvement compared to negative control.

Study Type

· Small Cohort study – hUC-MSCs vs. Negative control.

(The authors claim that this was a randomised trial, but they have not laid out detailed patient inclusion/exclusion criteria, and how the randomisation was performed).

Strengths and limitations of the paper

Novelty: This study highlights that there may be a potential role for human mesenchymal stem cell therapies in improving clinical outcomes in patients with COVID-19.

Standing in the field: At time of writing, multiple clinical trials examining the potential of human mesenchymal stem cells in COVID-19 therapy have been registered. This study is one of the first reporting outcomes in COVID-19 patients with human mesenchymal stem cells.

Appropriate statistics:

· Although outlining the use of appropriate statistical tests dependent on the normality of the data set, the authors do not explicitly lay out which statistical tests have been performed in their individual figures.

· At times there is a reliance on absolute comparisons rather than relative (inappropriate given that the control group sample size is more than double the intervention group)

Viral model used: N/A

Translatability: Large potential for translation: use of stem cell therapies in modulation of the immune response is well established.

Main limitations:

· Small cohort size.

· Unclear patient inclusion/exclusion criteria.

· Unclear as to whether co-morbidities have been accounted for and are consistant across both populations.

· Unclear what other management patients are receiving.

· Lack of mechanistic insight in the context of COVID-19.

· Towards the end of the paper the authors suggest that diabetics in their hUC-MSC population required less exogenous insulin compared to control, yet provide no evidence to support this claim.