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Can cell therapies halt cytokine storm in severe COVID-19 patients?

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Science Translational Medicine  22 Apr 2020:
Vol. 12, Issue 540, eabb5673
DOI: 10.1126/scitranslmed.abb5673

Abstract

A pilot study of COVID-19 patients treated with mesenchymal stem cells demonstrates safety.

Mesenchymal stromal cell (MSC) therapies, which have been explored for decades as a treatment for inflammatory diseases, are now being called into action to combat the cytokine storm induced by COVID-19. The severity of COVID-19 may be due in part to the patient’s response to the infection. In some patients, the virus induces an outpouring of inflammatory mediators that leads to swelling, inflammatory infiltration, and reduced gas exchange in the alveoli of the lungs. To combat this cytokine storm, over 20 clinical trials aiming to treat COVID-19 with MSCs have been registered with ClinicalTrials.gov.

Leng et al. recently conducted a pilot study of MSC transplantation in 10 patients in China. All patients tested positive for SARS-CoV-2 by polymerase chain reaction and had fever, shortness of breath, cough, and oxygen saturation at rest <95%. Seven of the patients received intravenous infusions of allogeneic MSCs while three received saline as a placebo control. All seven MSC treated patients experienced resolution of symptoms while one of the placebo-treated patients went on to develop ARDS and another died. The response of the most severely ill patient treated with MSCs was monitored throughout recovery. Of note, C-reactive protein levels dropped 10-fold after MSC treatment, suggesting a drop in systemic inflammation. Analysis of cytokine levels before and after treatment revealed that MSC treatment, but not placebo, was associated with a halt in the increase of serum tumor necrosis factor–α and an increase in anti-inflammatory interleukin-10 concentrations in the serum.

Although this study is not designed to make definitive claims regarding the efficacy of MSC therapy for COVID-19 or the mechanisms by which MSCs may function to prevent or treat cytokine storm, it does provide important safety data and hints of efficacy that have motivated further exploration of MSCs as a treatment for COVID-19. Of particular note is a randomized, multicenter, placebo-controlled, Phase 2/3 trial enrolling 240 patients being conducted through a public-private partnership between the U.S. National Institutes of Health–funded Cardiothoracic Surgical Trials Network and Mesoblast. As multiple clinical trials are launched around the world, we should not have to wait long to determine if MSCs are a viable and effective treatment option for severe COVID-19.

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