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Conquering the cytokine storm in COVID-19-induced ARDS using placenta-derived decidua stromal cells |
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| Authors: | Behnam Sadeghi Elham Roshandel Ali Pirsalehi Sepide Kazemi Ghazaleh Sankanian Mohammad Majidi Maryam Salimi Nasser Aghdami Hoda Sadrosadat Sarvenaz Samadi Kochaksaraei Farshid Alaeddini Olle Ringden Abbas Hajifathali |
| Affiliation: | 1. Translational Cell Therapy Research (TCR), Department of Clinical Science, Intervention and Technology, CLINTEC, Karolinska Institutet, Huddinge, Sweden;2. Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Project administration (equal), Visualization (equal), Writing - original draft (equal);3. Department of Internal Medicine, School of Medicine, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Contribution: Conceptualization (equal), Data curation (equal), Funding acquisition (equal), Investigation (equal), Methodology (equal), Project administration (equal), Supervision (equal), Validation (equal), Writing - original draft (equal);4. Translational Cell Therapy Research (TCR), Department of Clinical Science, Intervention and Technology, CLINTEC, Karolinska Institutet, Huddinge, Sweden Advanced Therapy Medicinal Product (ATMP), Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Project administration (equal), Validation (equal), Writing - original draft (equal);5. Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Writing - original draft (equal);6. Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Software (equal), Writing - original draft (equal);7. Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Contribution: Conceptualization (equal), Data curation (equal), Investigation (equal), Methodology (equal), Writing - original draft (equal);8. Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran Department of Infectious Diseases and Tropical Medicines, Tehran University of Medical Sciences, Tehran, Iran Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Supervision (equal), Writing - original draft (equal);9. Advanced Therapy Medicinal Product (ATMP), Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran Contribution: Conceptualization (equal), Data curation (equal), Investigation (equal), Methodology (equal), Writing - original draft (equal);10. Translational Cell Therapy Research (TCR), Department of Clinical Science, Intervention and Technology, CLINTEC, Karolinska Institutet, Huddinge, Sweden Advanced Therapy Medicinal Product (ATMP), Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran Contribution: Conceptualization (equal), Data curation (equal), Investigation (equal), Methodology (equal), Writing - original draft (equal);11. Research Center for Health Management in Mass Gathering, Red Crescent Society of the Islamic Republic of Iran, Tehran, Iran Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (lead), Investigation (equal), Methodology (equal), Writing - original draft (equal);12. Translational Cell Therapy Research (TCR), Department of Clinical Science, Intervention and Technology, CLINTEC, Karolinska Institutet, Huddinge, Sweden Contribution: Conceptualization (equal), Formal analysis (supporting), Funding acquisition (supporting), Investigation (supporting), Methodology (supporting), Resources (supporting), Writing - original draft (lead), Writing - review & editing (equal);13. Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran |
| Abstract: | Acute respiratory distress syndrome (ARDS) is the most common cause of death in COVID-19 patients. The cytokine storm is the main driver of the severity and magnitude of ARDS. Placenta-derived decidua stromal cells (DSCs) have a stronger immunosuppressive effect than other sources of mesenchymal stromal cells. Safety and efficacy study included 10 patients with a median age of 50 (range 14–68) years with COVID-19-induced ARDS. DSCs were administered 1–2 times at a dose of 1 × 106/kg. End points were safety and efficacy by survival, oxygenation and effects on levels of cytokines. Oxygenation levels increased from a median of 80.5% (range 69–88) to 95% (range 78–99) (p = 0.012), and pulmonary infiltrates disappeared in all patients. Levels of IL-6 decreased from a median of 69.3 (range 35.0–253.4) to 11 (range 4.0–38.3) pg/ml (p = 0.018), and CRP decreased from 69 (range 5–169) to 6 (range 2–31) mg/ml (p = 0.028). Two patients died, one of a myocardial infarction and the other of multiple organ failure, diagnosed before the DSC therapy. The other patients recovered and left the intensive care unit (ICU) within a median of 6 (range 3–12) days. DSC therapy is safe and capable of improving oxygenation, decreasing inflammatory cytokine level and clearing pulmonary infiltrates in patients with COVID-19. |
| Keywords: | COVID-19 cytokine storm decidua stromal cells intensive care unit survival |