GM-CSF ACTIVATES MYELOID CELLS TO DRIVE THE COVID-19 CYTOKINE STORM
Myeloid Cells in COVID-19
Overactive myeloid cells mediate tissue damage, hypercoagulation, and cytokine storm.
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Macrophage
Extensive infiltration of macrophages with a strong inflammatory phenotype in the upper and lower respiratory tracts
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Neutrophil
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Extensive infiltration of neutrophils in the lungs, which have been strongly implicated in the development of acute respiratory distress syndrome (ARDS)
Monocyte
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Unique population of inflammatory monocytes in the peripheral blood that have the capacity to secrete more GM-CSF
GM-CSF functions early in the cytokine storm cascade
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GM-CSF is produced locally in inflamed tissue as part of an anti-viral T-cell response to SARS-CoV-2 infection and functions to recruit and activate myeloid cells
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Once activated by GM-CSF, stimulated myeloid cells induce a hyperinflammatory response
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Consequences of the hyperinflammatory response include respiratory failure and other systemic complications
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References:
1.
Lang FM, Lee KM, Teijaro JR, Becher B, Hamilton JA. GM-CSF-based treatments in COVID-19: reconciling opposing therapeutic approaches. Nat Rev Immunol. 2020;20(8):507-514.
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Booz GW, Altara R, Eid AH, et al. Macrophage responses associated with COVID-19: a pharmacological perspective. Eur J Pharmacol. 2020;887:173547.
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Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180(7):934-943.
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Mehta P, Porter JC, Manson JJ, et al. Therapeutic blockade of granulocyte macrophage colony-stimulating factor in COVID-19-associated hyperinflammation: challenges and opportunities. Lancet Respir Med. 2020;8(8):822-830.
5.
Zhou Y, Fu B, Zheng X, et al. Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients. Natl Sci Rev. 2020;nwaa041.
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Blot M, Bour JB, Quenot JP, et al. The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome. J Transl Med. 2020;18(1):457.
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Pelaia C, Tinello C, Vatrella A, De Sarro G, Pelaia G. Lung under attack by COVID-19-induced cytokine storm: pathogenic mechanisms and therapeutic implications. Ther Adv Respir Dis. 2020;14:1753466620933508.
8.
Blot M, Bour JB, Quenot JP, et al. The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome. J Transl Med. 2020;18(1):457.