Myeloid-related protein-14 regulates deep vein thrombosis

Wang, Yunmei; Gao, Hanyu; Kessinger, Chase W.; Jaffer, Farouc A.; Simon, Daniel I.

doi:10.1172/jci.insight.91356

Cited by 26 publications

(29 citation statements)

References 60 publications

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“…NETs have been associated with the pathogenesis of ARDS ( Narasaraju et al., 2011 ; Middleton et al., 2020 ; Lefrançais et al., 2018 ) and thrombosis ( Ali et al., 2019 ), both phenotypes observed in severe COVID-19 patients, and elevated neutrophil counts predict worse outcomes in COVID-19 patients ( Wang et al., 2020a , 2020b ). Several NETs proteins that are also linked to thrombosis ( Wang et al., 2017 ; Healy et al., 2006 ), including calprotectin (S100A8/9), ferritin, CRP, and histone H3, were also increased in our cohort ( Table 1 ; Table S1 ). Thus, our data strengthen earlier suggestions (Barnes et al; Shen et al, 2020 ; Zuo et al, 2020 ) that combating dysregulated NETs may present an avenue toward mitigation of disease severity in COVID-19.…”

Section: Resultsmentioning

confidence: 65%

Large-Scale Multi-omic Analysis of COVID-19 Severity

et al. 2021

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We performed RNA-seq and high-resolution mass spectrometry on 128 blood samples from COVID-19-positive and COVID-19-negative patients with diverse disease severities and outcomes. Quantified transcripts, proteins, metabolites, and lipids were associated with clinical outcomes in a curated relational database, uniquely enabling systems analysis and cross-ome correlations to molecules and patient prognoses. We mapped 219 molecular features with high significance to COVID-19 status and severity, many of which were involved in complement activation, dysregulated lipid transport, and neutrophil activation. We identified sets of covarying molecules, e.g., protein gelsolin and metabolite citrate or plasmalogens and apolipoproteins, offering pathophysiological insights and therapeutic suggestions. The observed dysregulation of platelet function, blood coagulation, acute phase response, and endotheliopathy further illuminated the unique COVID-19 phenotype. We present a web-based tool (covid-omics.app) enabling interactive exploration of our compendium and illustrate its utility through a machine learning approach for prediction of COVID-19 severity.

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Section: Resultsmentioning

confidence: 65%

Large-Scale Multi-omic Analysis of COVID-19 Severity

et al. 2021

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“…NETs have been associated with the pathogenesis of ARDS ( Lefrançais et al, 2018 ; Middleton et al, 2020 ; Narasaraju et al, 2011 ) and thrombosis ( Ali et al, 2019 ), both phenotypes observed in severe COVID-19 patients, and elevated neutrophil counts predict worse outcomes in COVID-19 patients ( Wang et al, 2020a ). Interestingly, several NETs proteins that are also linked with thrombosis ( Healy et al, 2006 ; Wang et al, 2017 ), including calprotectin (S100A8/9), ferritin, CRP, and histone H3, were also increased in our cohort ( Table 1 and Supplementary Table 3 ). Thus our data suggest that combating dysregulated NETs may present an avenue towards mitigation of disease severity in COVID-19.…”

Section: Resultsmentioning

confidence: 71%

Large-scale Multi-omic Analysis of COVID-19 Severity

Overmyer

Miller

Balnis

et al. 2020

Preprint

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We performed RNA-Seq and high-resolution mass spectrometry on 128 blood samples from COVID-19 positive and negative patients with diverse disease severities. Over 17,000 transcripts, proteins, metabolites, and lipids were quantified and associated with clinical outcomes in a curated relational database, uniquely enabling systems analysis and cross-ome correlations to molecules and patient prognoses. We mapped 219 molecular features with high significance to COVID-19 status and severity, many involved in complement activation, dysregulated lipid transport, and neutrophil activation. We identified sets of covarying molecules, e.g., protein gelsolin and metabolite citrate or plasmalogens and apolipoproteins, offering pathophysiological insights and therapeutic suggestions. The observed dysregulation of platelet function, blood coagulation, acute phase response, and endotheliopathy further illuminated the unique COVID-19 phenotype. We present a web-based tool (covid-omics.app) enabling interactive exploration of our compendium and illustrate its utility through a comparative analysis with published data and a machine learning approach for prediction of COVID-19 severity.

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“…Depending on the system, calprotectin has been detected both upstream (31) and downstream (32) of IL-6, which has emerged as a possible therapeutic target in COVID-19. Calprotectin is also a potent stimulator of neutrophils themselves, promoting degranulation and phagocytosis (33,34), as well as other more recently described effector functions such as neutrophil extracellular trap (NET) release (35). Intriguingly, crosstalk between neutrophils, platelets, and calprotectin appears to play a role in both arterial and venous thrombosis (35,36), which are being increasingly identified as complications of COVID-19 (37,38).…”

Section: Discussionmentioning

confidence: 99%

Neutrophil calprotectin identifies severe pulmonary disease in COVID-19

Shi

Zuo

Yalavarthi

et al. 2020

Preprint

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Severe cases of coronavirus disease 2019 (COVID-19) are regularly complicated by respiratory failure. While it has been suggested that elevated levels of blood neutrophils associate with worsening oxygenation in COVID-19, it is unknown whether neutrophils are drivers of the thrombo-inflammatory storm or simple bystanders. To better understand the potential role of neutrophils in COVID-19, we measured levels of the neutrophil activation marker S100A8/A9 (calprotectin) in hospitalized patients and determined its relationship to severity of illness and respiratory status. Patients with COVID-19 (n=172) had markedly elevated levels of calprotectin in their blood. Calprotectin tracked with other acute phase reactants including C-reactive protein, ferritin, lactate dehydrogenase, and absolute neutrophil count, but was superior in identifying patients requiring mechanical ventilation. In longitudinal samples, calprotectin rose as oxygenation worsened. When tested on day 1 or 2 of hospitalization (n=94 patients), calprotectin levels were significantly higher in patients who progressed to severe COVID-19 requiring mechanical ventilation (8039 +/- 7031 ng/ml, n=32) as compared to those who remained free of intubation (3365 +/- 3146, p<0.0001). In summary, serum calprotectin levels track closely with current and future COVID-19 severity, implicating neutrophils as potential perpetuators of inflammation and respiratory compromise in COVID-19.

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Myeloid-related protein-14 regulates deep vein thrombosis

Cited by 26 publications

References 60 publications

Large-Scale Multi-omic Analysis of COVID-19 Severity

Large-Scale Multi-omic Analysis of COVID-19 Severity

Large-scale Multi-omic Analysis of COVID-19 Severity

Neutrophil calprotectin identifies severe pulmonary disease in COVID-19

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