PMC:7172841 / 92-1279 JSONTXT

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    LitCovid-PD-FMA-UBERON

    {"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T1","span":{"begin":388,"end":398},"obj":"Body_part"},{"id":"T2","span":{"begin":443,"end":452},"obj":"Body_part"},{"id":"T3","span":{"begin":472,"end":475},"obj":"Body_part"},{"id":"T4","span":{"begin":532,"end":543},"obj":"Body_part"},{"id":"T5","span":{"begin":550,"end":561},"obj":"Body_part"},{"id":"T6","span":{"begin":587,"end":592},"obj":"Body_part"},{"id":"T7","span":{"begin":630,"end":643},"obj":"Body_part"},{"id":"T8","span":{"begin":677,"end":686},"obj":"Body_part"},{"id":"T9","span":{"begin":776,"end":782},"obj":"Body_part"},{"id":"T10","span":{"begin":793,"end":796},"obj":"Body_part"},{"id":"T11","span":{"begin":964,"end":975},"obj":"Body_part"},{"id":"T12","span":{"begin":1083,"end":1086},"obj":"Body_part"},{"id":"T13","span":{"begin":1144,"end":1152},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"fma_id","subj":"T1","obj":"http://purl.org/sig/ont/fma/fma63261"},{"id":"A2","pred":"fma_id","subj":"T2","obj":"http://purl.org/sig/ont/fma/fma62852"},{"id":"A3","pred":"fma_id","subj":"T3","obj":"http://purl.org/sig/ont/fma/fma84795"},{"id":"A4","pred":"fma_id","subj":"T4","obj":"http://purl.org/sig/ont/fma/fma62863"},{"id":"A5","pred":"fma_id","subj":"T5","obj":"http://purl.org/sig/ont/fma/fma62863"},{"id":"A6","pred":"fma_id","subj":"T6","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A7","pred":"fma_id","subj":"T7","obj":"http://purl.org/sig/ont/fma/fma264829"},{"id":"A8","pred":"fma_id","subj":"T8","obj":"http://purl.org/sig/ont/fma/fma62864"},{"id":"A9","pred":"fma_id","subj":"T9","obj":"http://purl.org/sig/ont/fma/fma62970"},{"id":"A10","pred":"fma_id","subj":"T10","obj":"http://purl.org/sig/ont/fma/fma84795"},{"id":"A11","pred":"fma_id","subj":"T11","obj":"http://purl.org/sig/ont/fma/fma62863"},{"id":"A12","pred":"fma_id","subj":"T12","obj":"http://purl.org/sig/ont/fma/fma84795"},{"id":"A13","pred":"fma_id","subj":"T13","obj":"http://purl.org/sig/ont/fma/fma84050"}],"text":"Summary\nProper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7–8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation."}

    LitCovid-PD-MONDO

    {"project":"LitCovid-PD-MONDO","denotations":[{"id":"T3","span":{"begin":29,"end":37},"obj":"Disease"},{"id":"T4","span":{"begin":185,"end":204},"obj":"Disease"},{"id":"T5","span":{"begin":214,"end":222},"obj":"Disease"},{"id":"T6","span":{"begin":256,"end":274},"obj":"Disease"},{"id":"T7","span":{"begin":310,"end":318},"obj":"Disease"},{"id":"T8","span":{"begin":388,"end":418},"obj":"Disease"},{"id":"T9","span":{"begin":420,"end":423},"obj":"Disease"},{"id":"T10","span":{"begin":594,"end":599},"obj":"Disease"},{"id":"T11","span":{"begin":726,"end":742},"obj":"Disease"},{"id":"T12","span":{"begin":746,"end":755},"obj":"Disease"},{"id":"T13","span":{"begin":757,"end":765},"obj":"Disease"},{"id":"T14","span":{"begin":757,"end":761},"obj":"Disease"},{"id":"T15","span":{"begin":1036,"end":1044},"obj":"Disease"},{"id":"T16","span":{"begin":1105,"end":1116},"obj":"Disease"},{"id":"T17","span":{"begin":1174,"end":1186},"obj":"Disease"}],"attributes":[{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0021113"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0005046"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/MONDO_0015545"},{"id":"A9","pred":"mondo_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/MONDO_0015545"},{"id":"A10","pred":"mondo_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"},{"id":"A11","pred":"mondo_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/MONDO_0005229"},{"id":"A12","pred":"mondo_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/MONDO_0005812"},{"id":"A13","pred":"mondo_id","subj":"T13","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A14","pred":"mondo_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A15","pred":"mondo_id","subj":"T15","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A16","pred":"mondo_id","subj":"T16","obj":"http://purl.obolibrary.org/obo/MONDO_0003783"},{"id":"A17","pred":"mondo_id","subj":"T17","obj":"http://purl.obolibrary.org/obo/MONDO_0021166"}],"text":"Summary\nProper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7–8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation."}

    LitCovid-PD-CLO

    {"project":"LitCovid-PD-CLO","denotations":[{"id":"T1","span":{"begin":236,"end":237},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T2","span":{"begin":399,"end":409},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T3","span":{"begin":437,"end":442},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},{"id":"T4","span":{"begin":528,"end":531},"obj":"http://purl.obolibrary.org/obo/PR_000001004"},{"id":"T5","span":{"begin":545,"end":549},"obj":"http://purl.obolibrary.org/obo/CLO_0053432"},{"id":"T6","span":{"begin":582,"end":592},"obj":"http://purl.obolibrary.org/obo/CL_0000623"},{"id":"T7","span":{"begin":630,"end":643},"obj":"http://purl.obolibrary.org/obo/PR_000001393"},{"id":"T8","span":{"begin":677,"end":686},"obj":"http://purl.obolibrary.org/obo/CL_0000576"},{"id":"T9","span":{"begin":702,"end":703},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T10","span":{"begin":776,"end":782},"obj":"http://purl.obolibrary.org/obo/UBERON_0001969"},{"id":"T11","span":{"begin":881,"end":886},"obj":"http://purl.obolibrary.org/obo/CLO_0007225"}],"text":"Summary\nProper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7–8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation."}

    LitCovid-PD-CHEBI

    {"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T1","span":{"begin":453,"end":460},"obj":"Chemical"},{"id":"T2","span":{"begin":476,"end":478},"obj":"Chemical"},{"id":"T3","span":{"begin":645,"end":647},"obj":"Chemical"},{"id":"T5","span":{"begin":797,"end":799},"obj":"Chemical"},{"id":"T6","span":{"begin":851,"end":853},"obj":"Chemical"},{"id":"T8","span":{"begin":881,"end":886},"obj":"Chemical"},{"id":"T9","span":{"begin":1065,"end":1067},"obj":"Chemical"},{"id":"T11","span":{"begin":1087,"end":1089},"obj":"Chemical"}],"attributes":[{"id":"A1","pred":"chebi_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CHEBI_59132"},{"id":"A2","pred":"chebi_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CHEBI_73445"},{"id":"A3","pred":"chebi_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CHEBI_63895"},{"id":"A4","pred":"chebi_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CHEBI_74072"},{"id":"A5","pred":"chebi_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/CHEBI_73445"},{"id":"A6","pred":"chebi_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CHEBI_63895"},{"id":"A7","pred":"chebi_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CHEBI_74072"},{"id":"A8","pred":"chebi_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/CHEBI_35209"},{"id":"A9","pred":"chebi_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/CHEBI_63895"},{"id":"A10","pred":"chebi_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/CHEBI_74072"},{"id":"A11","pred":"chebi_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/CHEBI_73445"}],"text":"Summary\nProper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7–8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation."}

    LitCovid-PD-GO-BP

    {"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T1","span":{"begin":79,"end":91},"obj":"http://purl.obolibrary.org/obo/GO_0009405"},{"id":"T2","span":{"begin":287,"end":303},"obj":"http://purl.obolibrary.org/obo/GO_0006955"},{"id":"T3","span":{"begin":388,"end":409},"obj":"http://purl.obolibrary.org/obo/GO_0042116"},{"id":"T4","span":{"begin":600,"end":608},"obj":"http://purl.obolibrary.org/obo/GO_0070265"},{"id":"T5","span":{"begin":600,"end":608},"obj":"http://purl.obolibrary.org/obo/GO_0019835"},{"id":"T6","span":{"begin":600,"end":608},"obj":"http://purl.obolibrary.org/obo/GO_0008219"},{"id":"T7","span":{"begin":600,"end":608},"obj":"http://purl.obolibrary.org/obo/GO_0001906"},{"id":"T8","span":{"begin":644,"end":661},"obj":"http://purl.obolibrary.org/obo/GO_0032635"},{"id":"T9","span":{"begin":1144,"end":1163},"obj":"http://purl.obolibrary.org/obo/GO_0001816"},{"id":"T10","span":{"begin":1174,"end":1186},"obj":"http://purl.obolibrary.org/obo/GO_0006954"}],"text":"Summary\nProper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7–8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation."}

    LitCovid-sentences

    {"project":"LitCovid-sentences","denotations":[{"id":"T3","span":{"begin":0,"end":7},"obj":"Sentence"},{"id":"T4","span":{"begin":8,"end":92},"obj":"Sentence"},{"id":"T5","span":{"begin":93,"end":275},"obj":"Sentence"},{"id":"T6","span":{"begin":276,"end":348},"obj":"Sentence"},{"id":"T7","span":{"begin":349,"end":593},"obj":"Sentence"},{"id":"T8","span":{"begin":594,"end":756},"obj":"Sentence"},{"id":"T9","span":{"begin":757,"end":976},"obj":"Sentence"},{"id":"T10","span":{"begin":977,"end":1187},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Summary\nProper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7–8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation."}

    LitCovid-PD-HP

    {"project":"LitCovid-PD-HP","denotations":[{"id":"T3","span":{"begin":185,"end":204},"obj":"Phenotype"},{"id":"T4","span":{"begin":594,"end":599},"obj":"Phenotype"},{"id":"T5","span":{"begin":736,"end":742},"obj":"Phenotype"},{"id":"T6","span":{"begin":1005,"end":1025},"obj":"Phenotype"},{"id":"T7","span":{"begin":1105,"end":1116},"obj":"Phenotype"}],"attributes":[{"id":"A3","pred":"hp_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/HP_0002878"},{"id":"A4","pred":"hp_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/HP_0002664"},{"id":"A5","pred":"hp_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/HP_0100806"},{"id":"A6","pred":"hp_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/HP_0002958"},{"id":"A7","pred":"hp_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/HP_0001888"}],"text":"Summary\nProper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7–8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation."}

    LitCovid-PMC-OGER-BB

    {"project":"LitCovid-PMC-OGER-BB","denotations":[{"id":"T3","span":{"begin":29,"end":37},"obj":"SP_7"},{"id":"T4","span":{"begin":185,"end":196},"obj":"UBERON:0001004"},{"id":"T5","span":{"begin":214,"end":222},"obj":"SP_7"},{"id":"T6","span":{"begin":256,"end":262},"obj":"UBERON:0002405"},{"id":"T7","span":{"begin":287,"end":293},"obj":"UBERON:0002405;GO:0006955"},{"id":"T8","span":{"begin":294,"end":303},"obj":"GO:0006955"},{"id":"T9","span":{"begin":310,"end":318},"obj":"SP_7"},{"id":"T10","span":{"begin":388,"end":398},"obj":"CL:0000235;GO:0042116"},{"id":"T11","span":{"begin":399,"end":409},"obj":"GO:0042116"},{"id":"T12","span":{"begin":437,"end":442},"obj":"SP_6;NCBITaxon:9606"},{"id":"T13","span":{"begin":443,"end":452},"obj":"CL:0000738"},{"id":"T14","span":{"begin":453,"end":460},"obj":"CHEBI:59132;CHEBI:59132"},{"id":"T15","span":{"begin":472,"end":475},"obj":"PR:000029150"},{"id":"T16","span":{"begin":480,"end":490},"obj":"GO:0010467"},{"id":"T17","span":{"begin":528,"end":531},"obj":"PR:000001004"},{"id":"T18","span":{"begin":532,"end":543},"obj":"CL:0000542"},{"id":"T19","span":{"begin":545,"end":549},"obj":"PR:000001002"},{"id":"T20","span":{"begin":550,"end":561},"obj":"CL:0000542"},{"id":"T21","span":{"begin":567,"end":581},"obj":"CL:0000623"},{"id":"T22","span":{"begin":594,"end":617},"obj":"PR:000000134"},{"id":"T23","span":{"begin":619,"end":624},"obj":"PR:000000134"},{"id":"T24","span":{"begin":630,"end":643},"obj":"PR:000001393"},{"id":"T25","span":{"begin":645,"end":649},"obj":"PR:000001393"},{"id":"T26","span":{"begin":665,"end":676},"obj":"CL:0000080"},{"id":"T27","span":{"begin":677,"end":686},"obj":"CL:0000576"},{"id":"T28","span":{"begin":726,"end":735},"obj":"NCBITaxon:2"},{"id":"T29","span":{"begin":757,"end":767},"obj":"SP_7"},{"id":"T30","span":{"begin":776,"end":782},"obj":"UBERON:0001969"},{"id":"T31","span":{"begin":793,"end":796},"obj":"PR:000029150"},{"id":"T32","span":{"begin":800,"end":810},"obj":"GO:0010467"},{"id":"T33","span":{"begin":851,"end":855},"obj":"PR:000001393"},{"id":"T34","span":{"begin":864,"end":875},"obj":"DG_35"},{"id":"T35","span":{"begin":887,"end":898},"obj":"DG_35"},{"id":"T36","span":{"begin":952,"end":963},"obj":"CL:0000080"},{"id":"T37","span":{"begin":964,"end":975},"obj":"CL:0000542"},{"id":"T38","span":{"begin":1005,"end":1011},"obj":"UBERON:0002405"},{"id":"T39","span":{"begin":1012,"end":1025},"obj":"GO:0065007"},{"id":"T40","span":{"begin":1036,"end":1044},"obj":"SP_7"},{"id":"T41","span":{"begin":1065,"end":1069},"obj":"PR:000001393"},{"id":"T42","span":{"begin":1083,"end":1086},"obj":"PR:000029150"},{"id":"T43","span":{"begin":1090,"end":1100},"obj":"GO:0010467"},{"id":"T24276","span":{"begin":29,"end":37},"obj":"SP_7"},{"id":"T25589","span":{"begin":185,"end":196},"obj":"UBERON:0001004"},{"id":"T59726","span":{"begin":214,"end":222},"obj":"SP_7"},{"id":"T67700","span":{"begin":256,"end":262},"obj":"UBERON:0002405"},{"id":"T7839","span":{"begin":287,"end":293},"obj":"UBERON:0002405;GO:0006955"},{"id":"T23482","span":{"begin":294,"end":303},"obj":"GO:0006955"},{"id":"T94326","span":{"begin":310,"end":318},"obj":"SP_7"},{"id":"T55692","span":{"begin":388,"end":398},"obj":"CL:0000235;GO:0042116"},{"id":"T76896","span":{"begin":399,"end":409},"obj":"GO:0042116"},{"id":"T56154","span":{"begin":437,"end":442},"obj":"SP_6;NCBITaxon:9606"},{"id":"T45303","span":{"begin":443,"end":452},"obj":"CL:0000738"},{"id":"T92944","span":{"begin":453,"end":460},"obj":"CHEBI:59132;CHEBI:59132"},{"id":"T58214","span":{"begin":472,"end":475},"obj":"PR:000029150"},{"id":"T41859","span":{"begin":480,"end":490},"obj":"GO:0010467"},{"id":"T17537","span":{"begin":528,"end":531},"obj":"PR:000001004"},{"id":"T14494","span":{"begin":532,"end":543},"obj":"CL:0000542"},{"id":"T5373","span":{"begin":545,"end":549},"obj":"PR:000001002"},{"id":"T95317","span":{"begin":550,"end":561},"obj":"CL:0000542"},{"id":"T66709","span":{"begin":567,"end":581},"obj":"CL:0000623"},{"id":"T65169","span":{"begin":594,"end":617},"obj":"PR:000000134"},{"id":"T5325","span":{"begin":619,"end":624},"obj":"PR:000000134"},{"id":"T73676","span":{"begin":630,"end":643},"obj":"PR:000001393"},{"id":"T94520","span":{"begin":645,"end":649},"obj":"PR:000001393"},{"id":"T7633","span":{"begin":665,"end":676},"obj":"CL:0000080"},{"id":"T99503","span":{"begin":677,"end":686},"obj":"CL:0000576"},{"id":"T38740","span":{"begin":726,"end":735},"obj":"NCBITaxon:2"},{"id":"T85947","span":{"begin":757,"end":767},"obj":"SP_7"},{"id":"T29939","span":{"begin":776,"end":782},"obj":"UBERON:0001969"},{"id":"T8998","span":{"begin":793,"end":796},"obj":"PR:000029150"},{"id":"T62491","span":{"begin":800,"end":810},"obj":"GO:0010467"},{"id":"T78149","span":{"begin":851,"end":855},"obj":"PR:000001393"},{"id":"T18501","span":{"begin":864,"end":875},"obj":"DG_35"},{"id":"T10312","span":{"begin":887,"end":898},"obj":"DG_35"},{"id":"T74668","span":{"begin":952,"end":963},"obj":"CL:0000080"},{"id":"T90672","span":{"begin":964,"end":975},"obj":"CL:0000542"},{"id":"T2958","span":{"begin":1005,"end":1011},"obj":"UBERON:0002405"},{"id":"T86620","span":{"begin":1012,"end":1025},"obj":"GO:0065007"},{"id":"T3195","span":{"begin":1036,"end":1044},"obj":"SP_7"},{"id":"T88472","span":{"begin":1065,"end":1069},"obj":"PR:000001393"},{"id":"T6458","span":{"begin":1083,"end":1086},"obj":"PR:000029150"},{"id":"T72315","span":{"begin":1090,"end":1100},"obj":"GO:0010467"}],"text":"Summary\nProper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7–8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation."}

    LitCovid-PubTator

    {"project":"LitCovid-PubTator","denotations":[{"id":"36","span":{"begin":528,"end":531},"obj":"Gene"},{"id":"37","span":{"begin":545,"end":549},"obj":"Gene"},{"id":"38","span":{"begin":594,"end":617},"obj":"Gene"},{"id":"39","span":{"begin":619,"end":624},"obj":"Gene"},{"id":"40","span":{"begin":630,"end":643},"obj":"Gene"},{"id":"41","span":{"begin":645,"end":649},"obj":"Gene"},{"id":"42","span":{"begin":851,"end":855},"obj":"Gene"},{"id":"43","span":{"begin":1065,"end":1069},"obj":"Gene"},{"id":"44","span":{"begin":319,"end":327},"obj":"Species"},{"id":"45","span":{"begin":353,"end":361},"obj":"Species"},{"id":"46","span":{"begin":757,"end":767},"obj":"Species"},{"id":"47","span":{"begin":768,"end":775},"obj":"Species"},{"id":"48","span":{"begin":912,"end":920},"obj":"Species"},{"id":"49","span":{"begin":746,"end":755},"obj":"Species"},{"id":"50","span":{"begin":437,"end":442},"obj":"Species"},{"id":"51","span":{"begin":864,"end":875},"obj":"Chemical"},{"id":"52","span":{"begin":887,"end":898},"obj":"Chemical"},{"id":"53","span":{"begin":29,"end":37},"obj":"Disease"},{"id":"54","span":{"begin":185,"end":204},"obj":"Disease"},{"id":"55","span":{"begin":206,"end":209},"obj":"Disease"},{"id":"56","span":{"begin":214,"end":222},"obj":"Disease"},{"id":"57","span":{"begin":256,"end":274},"obj":"Disease"},{"id":"58","span":{"begin":310,"end":318},"obj":"Disease"},{"id":"59","span":{"begin":344,"end":347},"obj":"Disease"},{"id":"60","span":{"begin":367,"end":370},"obj":"Disease"},{"id":"61","span":{"begin":388,"end":418},"obj":"Disease"},{"id":"62","span":{"begin":736,"end":742},"obj":"Disease"},{"id":"63","span":{"begin":1036,"end":1044},"obj":"Disease"},{"id":"64","span":{"begin":1105,"end":1116},"obj":"Disease"},{"id":"65","span":{"begin":1168,"end":1186},"obj":"Disease"}],"attributes":[{"id":"A36","pred":"tao:has_database_id","subj":"36","obj":"Gene:920"},{"id":"A37","pred":"tao:has_database_id","subj":"37","obj":"Gene:930"},{"id":"A38","pred":"tao:has_database_id","subj":"38","obj":"Gene:7124"},{"id":"A39","pred":"tao:has_database_id","subj":"39","obj":"Gene:7124"},{"id":"A40","pred":"tao:has_database_id","subj":"40","obj":"Gene:3569"},{"id":"A41","pred":"tao:has_database_id","subj":"41","obj":"Gene:3569"},{"id":"A42","pred":"tao:has_database_id","subj":"42","obj":"Gene:3569"},{"id":"A43","pred":"tao:has_database_id","subj":"43","obj":"Gene:3569"},{"id":"A44","pred":"tao:has_database_id","subj":"44","obj":"Tax:9606"},{"id":"A45","pred":"tao:has_database_id","subj":"45","obj":"Tax:9606"},{"id":"A46","pred":"tao:has_database_id","subj":"46","obj":"Tax:2697049"},{"id":"A47","pred":"tao:has_database_id","subj":"47","obj":"Tax:9606"},{"id":"A48","pred":"tao:has_database_id","subj":"48","obj":"Tax:9606"},{"id":"A49","pred":"tao:has_database_id","subj":"49","obj":"Tax:11309"},{"id":"A50","pred":"tao:has_database_id","subj":"50","obj":"Tax:9606"},{"id":"A51","pred":"tao:has_database_id","subj":"51","obj":"MESH:C502936"},{"id":"A52","pred":"tao:has_database_id","subj":"52","obj":"MESH:C502936"},{"id":"A53","pred":"tao:has_database_id","subj":"53","obj":"MESH:C000657245"},{"id":"A54","pred":"tao:has_database_id","subj":"54","obj":"MESH:D012131"},{"id":"A56","pred":"tao:has_database_id","subj":"56","obj":"MESH:C000657245"},{"id":"A57","pred":"tao:has_database_id","subj":"57","obj":"MESH:D007154"},{"id":"A58","pred":"tao:has_database_id","subj":"58","obj":"MESH:C000657245"},{"id":"A61","pred":"tao:has_database_id","subj":"61","obj":"MESH:D055501"},{"id":"A62","pred":"tao:has_database_id","subj":"62","obj":"MESH:D018805"},{"id":"A63","pred":"tao:has_database_id","subj":"63","obj":"MESH:C000657245"},{"id":"A64","pred":"tao:has_database_id","subj":"64","obj":"MESH:D008231"},{"id":"A65","pred":"tao:has_database_id","subj":"65","obj":"MESH:D007249"}],"namespaces":[{"prefix":"Tax","uri":"https://www.ncbi.nlm.nih.gov/taxonomy/"},{"prefix":"MESH","uri":"https://id.nlm.nih.gov/mesh/"},{"prefix":"Gene","uri":"https://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"CVCL","uri":"https://web.expasy.org/cellosaurus/CVCL_"}],"text":"Summary\nProper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7–8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation."}