LitCovid-sentences  

PMC:7546716 / 20857-28450 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T81 0-58 Sentence denotes IL-33 and pathway synergisms in critical systemic COVID-19
T82 59-574 Sentence denotes In addition to NLRP3 stimulation and IL-1 release,47 substantial amounts of viroporins in patients with life-threatening COVID-19 might also account for extensive injury of alveolar epithelial cells and overproduction of IL-33.51 IL-33, IL-1α, and GM-CSF also stimulate each other's release by alveolar type 2 pneumocytes.52, 53 Accordingly, diffuse alveolar damage with alveolar denudation and reactive type 2 pneumocyte hyperplasia are histological hallmarks of COVID-19 with acute respiratory distress syndrome.4
T83 575-1876 Sentence denotes Feedforward loops might also engage mast cells, macrophages, endothelial cells, T cells, and neutrophils.40, 54 Although whether mast cells and macrophages produce IL-33 is still up for debate,51 it is well established that mast cells, infiltrating neutrophils, and cytotoxic T lymphocytes secrete serine proteases (eg, tryptase, cathepsin G, elastase, granzymes) that cleave IL-33 released from damaged epithelial and endothelial barriers into a mature form of IL-33 that is 10–30 times more active.51 IL-33 amplifies lung inflammation by inducing various proinflammatory cytokines (eg, GM-CSF, IL-1β, IL-6, TNF, granulocyte colony-stimulating factor [G-CSF]), chemokines (eg, CXCL1, CXCL2, CXCL6, CXCL8, CCL2, CCL20), and adhesion molecules (eg, E-selectin, ICAM1, VCAM1) in several target cells.32, 54, 55, 56, 57 Conversely, by inhibiting type 1 interferons and IL-12p35, IL-33 might contribute to impaired antiviral cytotoxic responses.58 In models of MAS-like disease, IL-33 is a crucial contributor to the weight loss and hyperferritinaemia related to systemic hyperinflammation, and to the expansion of GM-CSF-producing CD8+ T cells, upregulation of IL-1β and IL-6, and tissue neutrophilia.32 These features are the same as key characteristics seen in patients with critical COVID-19.5, 15, 26
T84 1877-2246 Sentence denotes IL-33 has also been implicated in the formation of neutrophil extracellular traps during virus-induced asthma exacerbation.58 Similarly, neutrophil priming with GM-CSF might promote the production of neutrophil extracellular traps.59 By releasing neutrophil elastase and other proteinases, neutrophil extracellular traps could in turn cleave and further activate IL-33.
T85 2247-2573 Sentence denotes These pathways might be relevant in patients with critical COVID-19, since neutrophilia and the neutrophil-to-lymphocyte ratio are associated with poor prognosis, and high concentrations of neutrophil extracellular traps have been detected in patients with COVID-19 admitted to hospital and receiving mechanical ventilation.60
T86 2574-3510 Sentence denotes Neutrophil extracellular traps might propagate inflammation and microvascular thrombosis in patients with COVID-19 and severe acute respiratory distress syndrome.60 Along with IL-33, IL-1, TNF, and other cytokines, neutrophil extracellular traps might increase endothelial permeability and induce a procoagulant phenotype in endothelial tissues by inducing expression of tissue factor,61, 62, 63 thus representing a possible link between hyperinflammation and hypercoagulability that could account for D-dimer elevation, pulmonary thrombosis, and microvascular manifestations affecting the heart, kidneys, and small bowel seen in patients with critical COVID-19.64, 65 Endothelialitis and endothelial dysfunction would also account for predominant exudative-phase diffuse alveolar damage characterised by hyaline membranes and fibrin deposits typically observed in patients with COVID-19 and severe acute respiratory distress syndrome.4
T87 3511-3838 Sentence denotes IL-33 has also been shown to stimulate expression of IL-1β, IL-6, CCL2, CXCL2, and G-CSF by adipocytes.57 Elevated circulating concentrations of soluble ST2 (measured more often than IL-33 because of its higher concentration and stability) are associated with obesity, diabetes, hypertension, and acute cardiovascular diseases.
T88 3839-4434 Sentence denotes High soluble ST2 concentrations also predict worse outcomes and are associated with extension of heart damage, heart failure, increased cardiovascular death, and all-cause mortality.54 Notably, diabetes, hypertension, and cardiovascular diseases are common comorbidities in patients with COVID-19, and obesity has been independently associated with increased severity and mortality among younger patients with COVID-19.66 Circulating concentrations of soluble ST2 correlate with the extent of tissue damage, and might represent an indicator in plasma of IL-33 release and bioactivity in tissues.
T89 4435-4782 Sentence denotes Production of soluble ST2 might be reduced by anti-ST2 treatment, and such reduction would modulate T-cell polarisation by decreasing pathogenic Th1 and Th17 cells, and increasing IL-10-producing Treg cells.67 Future research should focus on whether soluble ST2 concentrations in plasma have prognostic value in patients with COVID-19 (figure 2 ).
T90 4783-4849 Sentence denotes Figure 2 IL-33 might orchestrate all pathogenic phases of COVID-19
T91 4850-4959 Sentence denotes IL-33 might induce numerous cytokines and chemokines as well as its own receptor, ST2, in various cell types.
T92 4960-5201 Sentence denotes In asymptomatic or paucisymptomatic patients, IL-33 might expand anti-inflammatory Foxp3+ Treg cells or induce IL-4 production by GATA3+Foxp3+ Tregs and ILC2, thus stimulating mast cells, which might account for minor, allergy-like symptoms.
T93 5202-5396 Sentence denotes In individuals with mild-to-moderate disease, IL-33 (along with TGFβ) might induce ILC2 to release large amounts of IL-9, driving local expansion of effector memory Vγ9Vδ2+ T cells in the lungs.
T94 5397-5552 Sentence denotes In moderate–to-severe pneumonia, IL-33 combined with IL-2 and IL-7 from dendritic cells might further expand ILC2, γδT cells, and GM-CSF-producing T cells.
T95 5553-5676 Sentence denotes In severe–critical COVID-19, IL-33, GM-CSF, and IL-1 might stimulate each other's release by acting on multiple cell types.
T96 5677-5903 Sentence denotes IL-33 induction of cytokines, chemokines, adhesion molecules, tissue factor, and neutrophil extracellular traps might contribute to endothelialitis, thrombosis, and extrapulmonary involvement in patients with MAS-like disease.
T97 5904-6183 Sentence denotes Neutrophil extracellular traps and mast cell degranulation could provoke protease-mediated cleavage of IL-33 into a 10–30 times more potent form, and IL-33-induced release of its soluble receptor ST2 might further polarise T cells and contribute to cardiovascular manifestations.
T98 6184-6448 Sentence denotes In patients who survive, IL-33 might drive the post-acute fibrotic phase thorugh induction of IL-13 and TGFβ in M2-differentiated macrophages and ILC2, thereby stimulating myofibroblasts and eliciting the epithelial–to–mesenchymal transition of type 2 pneumocytes.
T99 6449-6612 Sentence denotes Molecules inside brackets are part of self-amplifying proinflammatory loops fed by IL-33 and outside brackets indicate different factors possibly induced by IL-33.
T100 6613-6720 Sentence denotes Question mark indicates the uncertainty of whether mast cells produce IL-33. bFGF=fibroblast growth factor.
T101 6721-6752 Sentence denotes CCL=C-C motif chemokine ligand.
T102 6753-6790 Sentence denotes CTGF=connective tissue growth factor.
T103 6791-6825 Sentence denotes CXCL=C-X-C motif chemokine ligand.
T104 6826-6905 Sentence denotes DIC=(systemic vascular thromboses mimicking) diffuse intravascular coagulation.
T105 6906-6944 Sentence denotes EMT=epithelial-mesenchymal transition.
T106 6945-6971 Sentence denotes Foxp=forkhead box protein.
T107 6972-6997 Sentence denotes GATA=GATA-binding factor.
T108 6998-7042 Sentence denotes G-CSF=granulocyte colony-stimulating factor.
T109 7043-7099 Sentence denotes GM-CSF=granulocyte-macrophage colony-stimulating factor.
T110 7100-7124 Sentence denotes ICU=intensive care unit.
T111 7125-7140 Sentence denotes IFN=interferon.
T112 7141-7156 Sentence denotes IL=interleukin.
T113 7157-7190 Sentence denotes ILC2=type 2 innate lymphoid cell.
T114 7191-7226 Sentence denotes MAS=macrophage activation syndrome.
T115 7227-7254 Sentence denotes MOF=multiple organ failure.
T116 7255-7289 Sentence denotes NET=neutrophil extracellular trap.
T117 7290-7326 Sentence denotes PDGF=platelet-derived growth factor.
T118 7327-7424 Sentence denotes P/F ratio=arterial oxygen partial pressure to fractional inspired oxygen ratio. sST2=soluble ST2.
T119 7425-7442 Sentence denotes ST2=ST2 receptor.
T120 7443-7474 Sentence denotes TGF=transforming growth factor.
T121 7475-7496 Sentence denotes TF-1=tissue factor-1.
T122 7497-7524 Sentence denotes TNF=tumour necrosis factor.
T123 7525-7569 Sentence denotes TRAIL=TNF-related apoptosis-inducing ligand.
T124 7570-7593 Sentence denotes Treg=regulatory T cell.