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LitCovid-PD-FMA-UBERON

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T52","span":{"begin":265,"end":269},"obj":"Body_part"},{"id":"T53","span":{"begin":304,"end":310},"obj":"Body_part"},{"id":"T54","span":{"begin":815,"end":820},"obj":"Body_part"},{"id":"T55","span":{"begin":3954,"end":3958},"obj":"Body_part"}],"attributes":[{"id":"A52","pred":"uberon_id","subj":"T52","obj":"http://purl.obolibrary.org/obo/UBERON_0001456"},{"id":"A53","pred":"uberon_id","subj":"T53","obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"A54","pred":"uberon_id","subj":"T54","obj":"http://purl.obolibrary.org/obo/UBERON_0001977"},{"id":"A55","pred":"uberon_id","subj":"T55","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"text":"COVID-19 and Leukocytes—Adding Fuel to the Thromboinflammatory Fire\nThe formation of NETs from activated neutrophils represents an innate immune response that aims to corral and kill invading pathogens. However, while having an important immune function, the Janus face of NETosis is the exacerbation of tissue injury, inflammation, and intravascular thrombosis. In the context of respiratory viruses, H1N1 infection has been linked to the excessive formation NETs in a mouse model of viral pneumonitis.95 Moreover, the infiltration of neutrophils at sites of infection and the risk of ARDS development has been demonstrated in a range of other pandemic respiratory viruses, such as H1N1, SARS-CoV, and MERS-CoV.107,108 There is now data demonstrating that patients with COVID-19 exhibit elevated levels of NETs in serum as measured by cell-free DNA, MPO-DNA, and citrullinated histone H3. The levels of MPO-DNA and citrullinated histone H3 were higher in patients receiving mechanical ventilation compared with those not requiring any supplemental oxygen suggesting that levels of NETs correlate with disease severity.109 Interestingly, the finding that the level of NETs correlated with elevations in D-dimer and sera from patients with COVID-19 could induce NETosis in purified neutrophils suggests that NETs, by way of their ability to generate thrombin, via activation of FXII, and activate platelets, may play an important role in mediating the prothrombotic phenotype observed in COVID-19.\nOne of the striking observations in severe COVID-19 is the correlation between inflammatory markers, such as CRP, ferritin and IL-6 and a raised D-dimer, the latter reporting on an activated coagulation pathway. Although a full discussion regarding the pathological hyperinflammatory response observed in severe COVID-19 is beyond the scope of this review, there is mounting evidence that monocytes/macrophages play a central role in this process.104 This is perhaps best highlighted by the observation that patients with severe COVID-19 in ICU exhibit a significant expansion of CD14+CD16+ monocytes producing IL-6 compared with nonhospitalized patients with COVID-19. As discussed above, this is particularly relevant in the context of thrombosis given the bidirectional relationship between monocytes and coagulation. First, activated platelets form heterotypic aggregates with monocytes in the setting of infection and inflammation. Platelet-monocyte aggregates may play a role in mechanical occlusion of the microvasculature in addition to altering platelet and monocyte functional responses.110,111 In this regard, platelets induce monocyte NF-κB (nuclear factor κ light-chain-enhancer of activated B cells) signaling and thereby modulate monocyte effector functions and induce the synthesis of the proinflammatory cytokines IL-8 and MCP-1.112 Moreover, platelet P-selectin induces monocyte TF expression and upregulates the expression of monocyte Mac-1 (αMβ2, CD11b/CD18).113,114 The platelet-derived chemokines, PF-4 and CXCL-12, enhance monocyte survival and facilitate differentiation into macrophages,115,116 while activated platelets also enhance the phagocytic activity of macrophages.117 A consistent feature of COVID-19 is the finding that patients with existing cardiovascular risk factors are at an increased risk of severe COVID-19 and have higher fatality rates from the disease.34,35 It is noteworthy that oxidized phospholipids, which are strongly associated with atherosclerosis, have been detected in the lungs of patients with SARS-CoV.118,119 OxPLs (oxidised phospholipids) are generated by reactive oxygen species and play important roles in regulating inflammation given their demonstrated roles in promoting monocyte TF production, monocyte activation, and endothelial cell activation.104 The oxidized phospholipid, oxPAPC, has been demonstrated to play a central role in the pathogenesis of a murine model of SARS-induced acute lung injury in a process linked to monocyte/macrophage activation via the TLR-4-TRIF-TRAF-6-NF-κB pathway.119"}

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PD-CHEBI

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T58","span":{"begin":3482,"end":3497},"obj":"Phenotype"},{"id":"T59","span":{"begin":3948,"end":3965},"obj":"Phenotype"}],"attributes":[{"id":"A58","pred":"hp_id","subj":"T58","obj":"http://purl.obolibrary.org/obo/HP_0002621"},{"id":"A59","pred":"hp_id","subj":"T59","obj":"http://www.orpha.net/ORDO/Orphanet_178320"}],"text":"COVID-19 and Leukocytes—Adding Fuel to the Thromboinflammatory Fire\nThe formation of NETs from activated neutrophils represents an innate immune response that aims to corral and kill invading pathogens. However, while having an important immune function, the Janus face of NETosis is the exacerbation of tissue injury, inflammation, and intravascular thrombosis. In the context of respiratory viruses, H1N1 infection has been linked to the excessive formation NETs in a mouse model of viral pneumonitis.95 Moreover, the infiltration of neutrophils at sites of infection and the risk of ARDS development has been demonstrated in a range of other pandemic respiratory viruses, such as H1N1, SARS-CoV, and MERS-CoV.107,108 There is now data demonstrating that patients with COVID-19 exhibit elevated levels of NETs in serum as measured by cell-free DNA, MPO-DNA, and citrullinated histone H3. The levels of MPO-DNA and citrullinated histone H3 were higher in patients receiving mechanical ventilation compared with those not requiring any supplemental oxygen suggesting that levels of NETs correlate with disease severity.109 Interestingly, the finding that the level of NETs correlated with elevations in D-dimer and sera from patients with COVID-19 could induce NETosis in purified neutrophils suggests that NETs, by way of their ability to generate thrombin, via activation of FXII, and activate platelets, may play an important role in mediating the prothrombotic phenotype observed in COVID-19.\nOne of the striking observations in severe COVID-19 is the correlation between inflammatory markers, such as CRP, ferritin and IL-6 and a raised D-dimer, the latter reporting on an activated coagulation pathway. Although a full discussion regarding the pathological hyperinflammatory response observed in severe COVID-19 is beyond the scope of this review, there is mounting evidence that monocytes/macrophages play a central role in this process.104 This is perhaps best highlighted by the observation that patients with severe COVID-19 in ICU exhibit a significant expansion of CD14+CD16+ monocytes producing IL-6 compared with nonhospitalized patients with COVID-19. As discussed above, this is particularly relevant in the context of thrombosis given the bidirectional relationship between monocytes and coagulation. First, activated platelets form heterotypic aggregates with monocytes in the setting of infection and inflammation. Platelet-monocyte aggregates may play a role in mechanical occlusion of the microvasculature in addition to altering platelet and monocyte functional responses.110,111 In this regard, platelets induce monocyte NF-κB (nuclear factor κ light-chain-enhancer of activated B cells) signaling and thereby modulate monocyte effector functions and induce the synthesis of the proinflammatory cytokines IL-8 and MCP-1.112 Moreover, platelet P-selectin induces monocyte TF expression and upregulates the expression of monocyte Mac-1 (αMβ2, CD11b/CD18).113,114 The platelet-derived chemokines, PF-4 and CXCL-12, enhance monocyte survival and facilitate differentiation into macrophages,115,116 while activated platelets also enhance the phagocytic activity of macrophages.117 A consistent feature of COVID-19 is the finding that patients with existing cardiovascular risk factors are at an increased risk of severe COVID-19 and have higher fatality rates from the disease.34,35 It is noteworthy that oxidized phospholipids, which are strongly associated with atherosclerosis, have been detected in the lungs of patients with SARS-CoV.118,119 OxPLs (oxidised phospholipids) are generated by reactive oxygen species and play important roles in regulating inflammation given their demonstrated roles in promoting monocyte TF production, monocyte activation, and endothelial cell activation.104 The oxidized phospholipid, oxPAPC, has been demonstrated to play a central role in the pathogenesis of a murine model of SARS-induced acute lung injury in a process linked to monocyte/macrophage activation via the TLR-4-TRIF-TRAF-6-NF-κB pathway.119"}

LitCovid-PD-GO-BP

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T115","span":{"begin":0,"end":67},"obj":"Sentence"},{"id":"T116","span":{"begin":68,"end":202},"obj":"Sentence"},{"id":"T117","span":{"begin":203,"end":362},"obj":"Sentence"},{"id":"T118","span":{"begin":363,"end":889},"obj":"Sentence"},{"id":"T119","span":{"begin":890,"end":1496},"obj":"Sentence"},{"id":"T120","span":{"begin":1497,"end":1708},"obj":"Sentence"},{"id":"T121","span":{"begin":1709,"end":2166},"obj":"Sentence"},{"id":"T122","span":{"begin":2167,"end":2317},"obj":"Sentence"},{"id":"T123","span":{"begin":2318,"end":2433},"obj":"Sentence"},{"id":"T124","span":{"begin":2434,"end":4063},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"COVID-19 and Leukocytes—Adding Fuel to the Thromboinflammatory Fire\nThe formation of NETs from activated neutrophils represents an innate immune response that aims to corral and kill invading pathogens. However, while having an important immune function, the Janus face of NETosis is the exacerbation of tissue injury, inflammation, and intravascular thrombosis. In the context of respiratory viruses, H1N1 infection has been linked to the excessive formation NETs in a mouse model of viral pneumonitis.95 Moreover, the infiltration of neutrophils at sites of infection and the risk of ARDS development has been demonstrated in a range of other pandemic respiratory viruses, such as H1N1, SARS-CoV, and MERS-CoV.107,108 There is now data demonstrating that patients with COVID-19 exhibit elevated levels of NETs in serum as measured by cell-free DNA, MPO-DNA, and citrullinated histone H3. The levels of MPO-DNA and citrullinated histone H3 were higher in patients receiving mechanical ventilation compared with those not requiring any supplemental oxygen suggesting that levels of NETs correlate with disease severity.109 Interestingly, the finding that the level of NETs correlated with elevations in D-dimer and sera from patients with COVID-19 could induce NETosis in purified neutrophils suggests that NETs, by way of their ability to generate thrombin, via activation of FXII, and activate platelets, may play an important role in mediating the prothrombotic phenotype observed in COVID-19.\nOne of the striking observations in severe COVID-19 is the correlation between inflammatory markers, such as CRP, ferritin and IL-6 and a raised D-dimer, the latter reporting on an activated coagulation pathway. Although a full discussion regarding the pathological hyperinflammatory response observed in severe COVID-19 is beyond the scope of this review, there is mounting evidence that monocytes/macrophages play a central role in this process.104 This is perhaps best highlighted by the observation that patients with severe COVID-19 in ICU exhibit a significant expansion of CD14+CD16+ monocytes producing IL-6 compared with nonhospitalized patients with COVID-19. As discussed above, this is particularly relevant in the context of thrombosis given the bidirectional relationship between monocytes and coagulation. First, activated platelets form heterotypic aggregates with monocytes in the setting of infection and inflammation. Platelet-monocyte aggregates may play a role in mechanical occlusion of the microvasculature in addition to altering platelet and monocyte functional responses.110,111 In this regard, platelets induce monocyte NF-κB (nuclear factor κ light-chain-enhancer of activated B cells) signaling and thereby modulate monocyte effector functions and induce the synthesis of the proinflammatory cytokines IL-8 and MCP-1.112 Moreover, platelet P-selectin induces monocyte TF expression and upregulates the expression of monocyte Mac-1 (αMβ2, CD11b/CD18).113,114 The platelet-derived chemokines, PF-4 and CXCL-12, enhance monocyte survival and facilitate differentiation into macrophages,115,116 while activated platelets also enhance the phagocytic activity of macrophages.117 A consistent feature of COVID-19 is the finding that patients with existing cardiovascular risk factors are at an increased risk of severe COVID-19 and have higher fatality rates from the disease.34,35 It is noteworthy that oxidized phospholipids, which are strongly associated with atherosclerosis, have been detected in the lungs of patients with SARS-CoV.118,119 OxPLs (oxidised phospholipids) are generated by reactive oxygen species and play important roles in regulating inflammation given their demonstrated roles in promoting monocyte TF production, monocyte activation, and endothelial cell activation.104 The oxidized phospholipid, oxPAPC, has been demonstrated to play a central role in the pathogenesis of a murine model of SARS-induced acute lung injury in a process linked to monocyte/macrophage activation via the TLR-4-TRIF-TRAF-6-NF-κB pathway.119"}

2_test

{"project":"2_test","denotations":[{"id":"32586214-21703402-21597773","span":{"begin":503,"end":505},"obj":"21703402"},{"id":"32586214-16322745-21597774","span":{"begin":712,"end":715},"obj":"16322745"},{"id":"32586214-26980924-21597775","span":{"begin":716,"end":719},"obj":"26980924"},{"id":"32586214-32376901-21597776","span":{"begin":1944,"end":1947},"obj":"32376901"},{"id":"32586214-11994242-21597777","span":{"begin":2594,"end":2597},"obj":"11994242"},{"id":"32586214-18723438-21597778","span":{"begin":2598,"end":2601},"obj":"18723438"},{"id":"32586214-18684880-21597779","span":{"begin":2843,"end":2846},"obj":"18684880"},{"id":"32586214-7522321-21597780","span":{"begin":2976,"end":2979},"obj":"7522321"},{"id":"32586214-10551687-21597781","span":{"begin":2980,"end":2983},"obj":"10551687"},{"id":"32586214-26583329-21597782","span":{"begin":3109,"end":3112},"obj":"26583329"},{"id":"32586214-10666185-21597783","span":{"begin":3113,"end":3116},"obj":"10666185"},{"id":"32586214-27895175-21597784","span":{"begin":3195,"end":3198},"obj":"27895175"},{"id":"32586214-32173574-21597785","span":{"begin":3395,"end":3397},"obj":"32173574"},{"id":"32586214-16000355-21597786","span":{"begin":3557,"end":3560},"obj":"16000355"},{"id":"32586214-18423196-21597787","span":{"begin":3561,"end":3564},"obj":"18423196"},{"id":"32586214-32376901-21597788","span":{"begin":3810,"end":3813},"obj":"32376901"},{"id":"32586214-18423196-21597789","span":{"begin":4060,"end":4063},"obj":"18423196"}],"text":"COVID-19 and Leukocytes—Adding Fuel to the Thromboinflammatory Fire\nThe formation of NETs from activated neutrophils represents an innate immune response that aims to corral and kill invading pathogens. However, while having an important immune function, the Janus face of NETosis is the exacerbation of tissue injury, inflammation, and intravascular thrombosis. In the context of respiratory viruses, H1N1 infection has been linked to the excessive formation NETs in a mouse model of viral pneumonitis.95 Moreover, the infiltration of neutrophils at sites of infection and the risk of ARDS development has been demonstrated in a range of other pandemic respiratory viruses, such as H1N1, SARS-CoV, and MERS-CoV.107,108 There is now data demonstrating that patients with COVID-19 exhibit elevated levels of NETs in serum as measured by cell-free DNA, MPO-DNA, and citrullinated histone H3. The levels of MPO-DNA and citrullinated histone H3 were higher in patients receiving mechanical ventilation compared with those not requiring any supplemental oxygen suggesting that levels of NETs correlate with disease severity.109 Interestingly, the finding that the level of NETs correlated with elevations in D-dimer and sera from patients with COVID-19 could induce NETosis in purified neutrophils suggests that NETs, by way of their ability to generate thrombin, via activation of FXII, and activate platelets, may play an important role in mediating the prothrombotic phenotype observed in COVID-19.\nOne of the striking observations in severe COVID-19 is the correlation between inflammatory markers, such as CRP, ferritin and IL-6 and a raised D-dimer, the latter reporting on an activated coagulation pathway. Although a full discussion regarding the pathological hyperinflammatory response observed in severe COVID-19 is beyond the scope of this review, there is mounting evidence that monocytes/macrophages play a central role in this process.104 This is perhaps best highlighted by the observation that patients with severe COVID-19 in ICU exhibit a significant expansion of CD14+CD16+ monocytes producing IL-6 compared with nonhospitalized patients with COVID-19. As discussed above, this is particularly relevant in the context of thrombosis given the bidirectional relationship between monocytes and coagulation. First, activated platelets form heterotypic aggregates with monocytes in the setting of infection and inflammation. Platelet-monocyte aggregates may play a role in mechanical occlusion of the microvasculature in addition to altering platelet and monocyte functional responses.110,111 In this regard, platelets induce monocyte NF-κB (nuclear factor κ light-chain-enhancer of activated B cells) signaling and thereby modulate monocyte effector functions and induce the synthesis of the proinflammatory cytokines IL-8 and MCP-1.112 Moreover, platelet P-selectin induces monocyte TF expression and upregulates the expression of monocyte Mac-1 (αMβ2, CD11b/CD18).113,114 The platelet-derived chemokines, PF-4 and CXCL-12, enhance monocyte survival and facilitate differentiation into macrophages,115,116 while activated platelets also enhance the phagocytic activity of macrophages.117 A consistent feature of COVID-19 is the finding that patients with existing cardiovascular risk factors are at an increased risk of severe COVID-19 and have higher fatality rates from the disease.34,35 It is noteworthy that oxidized phospholipids, which are strongly associated with atherosclerosis, have been detected in the lungs of patients with SARS-CoV.118,119 OxPLs (oxidised phospholipids) are generated by reactive oxygen species and play important roles in regulating inflammation given their demonstrated roles in promoting monocyte TF production, monocyte activation, and endothelial cell activation.104 The oxidized phospholipid, oxPAPC, has been demonstrated to play a central role in the pathogenesis of a murine model of SARS-induced acute lung injury in a process linked to monocyte/macrophage activation via the TLR-4-TRIF-TRAF-6-NF-κB pathway.119"}

LitCovid-PubTator

PMC:7386875 / 34520-38583 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:7386875 / 34520-38583 JSON TXT