IMECOV19: Immune Modulation by Exosomes in COVID-19
Study Details
Study Description
Brief Summary
Following whole blood stimulation with mesenchymal stem cell derived exosomes, immune phenotype, cytokine release and mRNA expression patterns from critically ill patients with COVID-19 will be determined.
Condition or Disease | Intervention/Treatment | Phase |
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Detailed Description
Critically ill patients with COVID-19 may develop lung failure and require extracorporal oxygenation due to hyperinflammation and progressive lung fibrosis. The anti-inflammatory and immune modulatory function of mesenchymal stem cells will be investigated by whole blood stimulation experiments using stem cell derived exosomes. Exosome preparations have been characterized by miRNA and protein expression patterns and suggest their tissue regenerative capacity.
The hypothesis of the present study is that mesenchymal stem cell derived exosomes attenuate inflammation and support anti-fibrotic pathways.
Study Design
Outcome Measures
Primary Outcome Measures
- Cytokine profile in supernatants [24 hours, 1 year]
Quantification of pro- and anti-inflammatory biomarkers after 24 hours of whole blood culture
Secondary Outcome Measures
- Immune phenotyping [1 year]
Immune phenotypes related to type I interferon signaling
- Genetic predisposition to hyperinflammation [1 year]
Determination of functional single nucleotide polymorphisms of inflammatory genes and receptors
Eligibility Criteria
Criteria
Inclusion Criteria:
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Critically ill COVID-19 patients with lung dysfunction
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COVID-19 WHO severity degree >= 4, ARDS (WHO Definition 13 March 2020)
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Body weight > 50 kg
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Informed consent
Exclusion Criteria:
- Pregnant or breast feeding women
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Ulm University Hospital, Clinic of Anesthesiology and Intensive Care Medicine | Ulm | Germany | 89070 |
Sponsors and Collaborators
- University of Ulm
Investigators
- Principal Investigator: Manfred Weiss, MD, Clinic of Anaesthesiology and Intensive Care Medicine
- Principal Investigator: Marion Schneider, PhD, Clinic of Anaesthesiology and Intensive Care Medicine
Study Documents (Full-Text)
None provided.More Information
Publications
- Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017 Jul;39(5):529-539. doi: 10.1007/s00281-017-0629-x. Epub 2017 May 2. Review.
- Di Rocco G, Baldari S, Toietta G. Towards Therapeutic Delivery of Extracellular Vesicles: Strategies for In Vivo Tracking and Biodistribution Analysis. Stem Cells Int. 2016;2016:5029619. Epub 2016 Nov 23. Review.
- Geistlinger J, Du W, Groll J, Liu F, Hoegel J, Foehr KJ, Pasquarelli A, Schneider EM. P2RX7 genotype association in severe sepsis identified by a novel Multi-Individual Array for rapid screening and replication of risk SNPs. Clin Chim Acta. 2012 Jan 18;413(1-2):39-47. doi: 10.1016/j.cca.2011.05.023. Epub 2011 May 25.
- Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A, Antonakos N, Damoraki G, Gkavogianni T, Adami ME, Katsaounou P, Ntaganou M, Kyriakopoulou M, Dimopoulos G, Koutsodimitropoulos I, Velissaris D, Koufargyris P, Karageorgos A, Katrini K, Lekakis V, Lupse M, Kotsaki A, Renieris G, Theodoulou D, Panou V, Koukaki E, Koulouris N, Gogos C, Koutsoukou A. Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure. Cell Host Microbe. 2020 Jun 10;27(6):992-1000.e3. doi: 10.1016/j.chom.2020.04.009. Epub 2020 Apr 21.
- Gotts JE, Matthay MA. Endogenous and exogenous cell-based pathways for recovery from acute respiratory distress syndrome. Clin Chest Med. 2014 Dec;35(4):797-809. doi: 10.1016/j.ccm.2014.08.015. Epub 2014 Sep 24. Review.
- Häberle H, Magunia H, Lang P, Gloeckner H, Körner A, Koeppen M, Backchoul T, Malek N, Handgretinger R, Rosenberger P, Mirakaj V. Mesenchymal Stem Cell Therapy for Severe COVID-19 ARDS. J Intensive Care Med. 2021 Jun;36(6):681-688. doi: 10.1177/0885066621997365. Epub 2021 Mar 5.
- J. Bindja, M. E. Weiss, M. Schmolz, G. M. Stein, J. Mapes, N. Schneiderhan-Marra, T. O. Joos, E. M. Schneider. Synthetic ligands against TLR2-9 in TruCulture™ - whole blood assays distinguish clinical stages of SIRS (trauma) and sepsis.Trauma, Shock, Inflammation and Sepsis.Trauma, Shock, Inflammation and Sepsis - TSIS 2010; 55 - 63
- Lai RC, Arslan F, Lee MM, Sze NS, Choo A, Chen TS, Salto-Tellez M, Timmers L, Lee CN, El Oakley RM, Pasterkamp G, de Kleijn DP, Lim SK. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010 May;4(3):214-22. doi: 10.1016/j.scr.2009.12.003. Epub 2010 Jan 4.
- Leng Z, Zhu R, Hou W, Feng Y, Yang Y, Han Q, Shan G, Meng F, Du D, Wang S, Fan J, Wang W, Deng L, Shi H, Li H, Hu Z, Zhang F, Gao J, Liu H, Li X, Zhao Y, Yin K, He X, Gao Z, Wang Y, Yang B, Jin R, Stambler I, Lim LW, Su H, Moskalev A, Cano A, Chakrabarti S, Min KJ, Ellison-Hughes G, Caruso C, Jin K, Zhao RC. Transplantation of ACE2(-) Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Aging Dis. 2020 Mar 9;11(2):216-228. doi: 10.14336/AD.2020.0228. eCollection 2020 Apr.
- Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16.
- Monsel A, Zhu YG, Gudapati V, Lim H, Lee JW. Mesenchymal stem cell derived secretome and extracellular vesicles for acute lung injury and other inflammatory lung diseases. Expert Opin Biol Ther. 2016 Jul;16(7):859-71. doi: 10.1517/14712598.2016.1170804. Epub 2016 Apr 12. Review.
- Shah TG, Predescu D, Predescu S. Mesenchymal stem cells-derived extracellular vesicles in acute respiratory distress syndrome: a review of current literature and potential future treatment options. Clin Transl Med. 2019 Sep 12;8(1):25. doi: 10.1186/s40169-019-0242-9. Review.
- Shi L, Huang H, Lu X, Yan X, Jiang X, Xu R, Wang S, Zhang C, Yuan X, Xu Z, Huang L, Fu JL, Li Y, Zhang Y, Yao WQ, Liu T, Song J, Sun L, Yang F, Zhang X, Zhang B, Shi M, Meng F, Song Y, Yu Y, Wen J, Li Q, Mao Q, Maeurer M, Zumla A, Yao C, Xie WF, Wang FS. Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: a randomized, double-blind, placebo-controlled phase 2 trial. Signal Transduct Target Ther. 2021 Feb 10;6(1):58. doi: 10.1038/s41392-021-00488-5.
- Shi L, Wang L, Xu R, Zhang C, Xie Y, Liu K, Li T, Hu W, Zhen C, Wang FS. Mesenchymal stem cell therapy for severe COVID-19. Signal Transduct Target Ther. 2021 Sep 8;6(1):339. doi: 10.1038/s41392-021-00754-6. Review.
- Shi Y, Wang Y, Shao C, Huang J, Gan J, Huang X, Bucci E, Piacentini M, Ippolito G, Melino G. COVID-19 infection: the perspectives on immune responses. Cell Death Differ. 2020 May;27(5):1451-1454. doi: 10.1038/s41418-020-0530-3. Epub 2020 Mar 23.
- Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24. Erratum in: Lancet Respir Med. 2020 Apr;8(4):e26.
- Lung fibrosis in COVID19