Corpus overview


MeSH Disease

Human Phenotype


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    Markers Of Coagulation And Hemostatic Activation Identify COVID-19 Patients At High Risk For Thrombotic Events MESHD, ICU Admission and Intubation

    Authors: Darwish Alabyad; Srikant Rangaraju; Michael Liu; Rajeel Imran; Christine Kempton; Milad Sharifpour; Sara Auld; Manila Gaddh; Roman Sniecinski; Cheryl L Maier; Jeannette Guarner; Alexander Duncan; Fadi Nahab

    doi:10.1101/2020.10.04.20206540 Date: 2020-10-06 Source: medRxiv

    Background: Coronavirus disease 2019 (COVID-19) has been associated with a coagulopathy giving rise to venous and arterial thrombotic MESHD events. The objective of our study was to determine whether markers of coagulation MESHD and hemostatic activation (MOCHA) on admission could identify COVID-19 patients at risk for thrombotic MESHD events and other complications. Methods: COVID-19 patients admitted to a tertiary academic healthcare system from April 3, 2020 to July 31, 2020 underwent standardized admission testing of MOCHA profile parameters ( plasma SERO d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer) with abnormal MOCHA defined as [≥] 2 markers above the reference. Prespecified thrombotic MESHD endpoints included deep vein thrombosis MESHD, pulmonary embolism HP pulmonary embolism MESHD, myocardial infarction HP myocardial infarction MESHD, ischemic stroke HP ischemic stroke MESHD, and access line thrombosis MESHD; other complications included ICU admission, intubation and mortality. We excluded patients on anticoagulation therapy prior to admission and those who were pregnant. Results: Of 276 patients (mean age TRANS 59 {+/-} 6.4 years, 47% female TRANS, 62% African American race) who met study criteria, 45 (16%) had a thrombotic MESHD event. Each coagulation marker on admission was independently associated with a vascular endpoint (p<0.05). Admission MOCHA with [≥] 2 abnormalities (n=203, 74%) was associated with in-hospital vascular endpoints (OR 3.3, 95% CI 1.2-8.8), as were admission D-dimer [≥] 2000 ng/mL (OR 3.1, 95% CI 1.5-6.6), and admission D-dimer [≥] 3000 ng/mL (OR 3.6, 95% CI 1.6-7.9). However, only admission MOCHA with [≥] 2 abnormalities was associated with ICU admission (OR 3.0, 95% CI 1.7-5.2) and intubation (OR 3.2, 95% CI 1.6-6.4), while admission D-dimer [≥] 2000 ng/mL and admission D-dimer [≥] 3000 ng/mL were not associated. MOCHA and D-dimer cutoffs were not associated with mortality. Admission MOCHA with <2 abnormalities (26% of the cohort) had a sensitivity SERO of 88% and negative predictive value SERO of 93% for a vascular endpoint. Conclusions: Admission MOCHA with [≥] 2 abnormalities identified COVID-19 patients at increased risk of ICU admission and intubation during hospitalization more effectively than isolated admission D-dimer measurement. Admission MOCHA with <2 abnormalities identified a subgroup of patients at low risk for vascular events. Our results suggest that an admission MOCHA profile can be useful to risk-stratify COVID-19 patients.

    Comparing biomarkers for COVID-19 disease with commonly associated preexisting conditions and complications.

    Authors: Jesse Huang; Aditya M Rao; Denis Dermadi; Jiaying Toh; Lara Murphy Jones; Michele Donato; Yiran Liu; Yapeng Su; Minas Karagiannis; Theodoros Marantos; Yehudit Hasin-Brumshtein; Yudong D He; Evangelos J Giamarellos-Bourboulis; Jim Heath; Purvesh Khatri

    doi:10.1101/2020.10.02.20205609 Date: 2020-10-05 Source: medRxiv

    Severe coronavirus disease MESHD 2019 (COVID-19) has been associated with certain preexisting health conditions and can cause respiratory failure HP respiratory failure MESHD along with other multi-organ injuries. However, the mechanism of these relationships is unclear, and prognostic biomarkers for the disease and its systemic complications are lacking. This study aims to examine the plasma SERO protein profile of COVID-19 patients and evaluate overlapping protein modules with biomarkers of common comorbidities. Blood SERO samples were collected from COVID-19 cases (n=307) and negative controls (n=78) among patients with acute respiratory distress MESHD respiratory distress HP. Proteins were measured by proximity extension assay utilizing next-generation sequencing technology. Its associations to COVID-19 disease characteristics were compared to that of preexisting conditions and established biomarkers for myocardial infarction HP myocardial infarction MESHD ( MI MESHD), stroke HP stroke MESHD, hypertension HP hypertension MESHD, diabetes MESHD, smoking, and chronic kidney disease HP chronic kidney disease MESHD. Several proteins were differentially expressed in COVID-19, including multiple pro-inflammatory cytokines such as IFN-gamma, CXCL10, and CCL7/MCP-3. Elevated IL-6 was associated with increased severity, while baseline IL1RL1/ST2 levels were associated with a worse prognosis. Network analysis identified several protein modules associated with COVID-19 disease characteristics overlapping with processes of preexisting hypertension HP hypertension MESHD and impaired kidney function MESHD. BNP and NTpro-BNP, markers for MI MESHD and stroke HP stroke MESHD, increased with disease progression and were positively associated with severity. MMP12 was similarly elevated and has been previously linked to smoking and inflammation in emphysema MESHD emphysema HP, along with increased cardiovascular disease MESHD risk. In conclusion, this study provides an overview of the systemic effects of COVID-19 and candidate biomarkers for clinical assessment of disease progression and the risk of systemic complications.

    Ethnically diverse mutations in PIEZO1 associate with SARS-CoV-2 positivity

    Authors: Chew W Cheng; Vijayalakshmi Deivasikamani; Melanie J Ludlow; Dario De Vecchis; Antreas C Kalli; David J Beech; Piruthivi Sukumar

    doi:10.1101/2020.06.01.20119651 Date: 2020-06-03 Source: medRxiv

    COVID-19, caused by the SARS-CoV-2 virus, carries significant risk of mortality and has spread globally with devastating societal consequences. Endothelial infection MESHD has been identified as a feature of the disease and so there is motivation to determine the relevance of endothelial membrane mechanisms affecting viral entry and response. Here, through a study of patient data in UK Biobank released on 16 April 2020, we suggest relevance of PIEZO1, a non-selective cation channel protein that both mediates endothelial responses to mechanical force and unusually indents the cell membrane. PIEZO1 notably has roles that may also be relevant in red blood SERO cell function, pulmonary inflammation MESHD, bacterial infection MESHD and fibrotic auto-inflammation MESHD. We provide evidence that single nucleotide polymorphisms (SNPs) in the gene encoding PIEZO1 are more common in individuals who test positive for SARS-CoV-2 regardless of pre-existing hypertension HP hypertension MESHD, myocardial infarction HP myocardial infarction MESHD, stroke HP stroke MESHD, diabetes mellitus HP diabetes mellitus MESHD or arthritis HP arthritis MESHD. Some of these SNPs are more common in African and Caribbean populations, which are groups that were recently shown to have greater susceptibility to infection. One of the SNPs is a missense mutation that results in an amino acid change in an evolutionarily conserved and previously unexplored N-terminal region PIEZO1. The data support the notion of genetic factors influencing SARS-CoV-2 infection MESHD and suggest a specific role for PIEZO1.

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MeSH Disease
Human Phenotype

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