Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia

By Zikuan Leng, Rongjia Zhu, W. Hou, Yingmei Feng, Yanlei Yang, Q. Han, G. Shan, F. Meng, Dongshu Du, Shihua Wang and 28 more. Aging and Disease, 2020

915 citations recorded by the source corpus.

A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China, from Jan 23, 2020 to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokine-secreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11bmid regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2- and TMPRSS2- which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.

Subfields: Genetics, Infectious Diseases, Neurology

View Paper: https://www.semanticscholar.org/paper/1f08d9459ae9d56cf7ba63b9f5b42d59cc9679a6

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1. Yuefei Jin
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Citations in the corpus

• Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach (2020, neutral): “[148] on patients with COVID-19, suggested that intravenous transplantation of MSCs into patients is effective in the treatment of COVID-19 with lesser side effects.”
• SARS-CoV-2 infection: The role of cytokines in COVID-19 disease (2020, neutral): “MSCs inhibit the secretion of IL-12, as well as IFN-γ and TNF-α, and have been proposed as an effective therapy against COVID-19 [144,145].”
• Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment (2020, background): “concluded that IV transplantation of MSCs was safe and effective in patients with COVID-19 pneumonia, especially for those in critically severe conditions [67].”
• The cytokine storm and COVID‐19 (2020, background): “A clinical trial of MSC therapy revealed that MSCs were able to rapidly and significantly improve the clinical symptoms of COVID‐19 without any observed adverse effects.(72) Although the side effects of MSC treatment are rarely reported, the safety and”
• Virology, Epidemiology, Pathogenesis, and Control of COVID-19 (2020, background): “with immunoglobulin (IVIG), and systemic anti-inflammatory drugs to reduce cytokine storm are also potential therapeutic strategies for severe COVID-19 [61,79].”
• Exosomes Derived from Bone Marrow Mesenchymal Stem Cells as Treatment for Severe COVID-19 (2020, neutral): “…mesenchymal stem cell (bmMSC) transplantation has shown promise, with trials currently underway, this technology is limited by safety, cell survivability, scalability, and regulatory issues that make it an impractical option to meet the needs of millions of infected patients worldwide [12–14].”