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Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
    displaying 1 - 7 records in total 7
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    Pleotropic association between risk and prognosis of COVID-19 and gene expression in blood SERO and lung: A Mendelian randomization analysis

    Authors: Di Liu; Jingyun Yang; Bowen Feng; Wenjin Lu; Chuntao Zhao; Lizhuo Li; William Page; Ernest Guignon; Arturo Pilar; George N Gibson; - the Yale IMPACT Research Team; Charles S. Dela Cruz; Shelli F. Farhadian; Akiko Iwasaki; Albert I. Ko; Nathan D. Grubaugh; Anne L. Wyllie

    doi:10.1101/2020.09.02.20187179 Date: 2020-09-03 Source: medRxiv

    Background: Coronavirus disease 2019 (COVID-19) has caused a large global pandemic. Patients with COVID-19 exhibited considerable variation in disease behavior. Pervious genome-wide association studies ( GWAS MESHD) have identified potential genetic factors involved in the risk and prognosis of COVID-19, but the underlying biological interpretation remains largely unclear. Methods: We applied the summary data-based Mendelian randomization (SMR) method to identify genes that were pleiotropically/potentially causally associated with the risk and various outcomes of COVID-19, including severe respiratory confirmed COVID-19 and hospitalized COVID-19. The GWAS summarized data for COVID-19 were provided by the COVID-19 Host Genetics Initiative and the Severe Covid-19 GWAS Group. Analyses were done for blood SERO and lung, respectively. Results: In blood SERO, we identified 2 probes, ILMN_1765146 and ILMN_1791057 tagging IFNAR2, that showed pleiotropic association with hospitalized COVID-19 (beta [SE]=0.42 [0.09], P=4.75E06 and beta [SE]=-0.48 [0.11], P=6.76E06, respectively). Although no other probes were significant after correction for multiple testing in both blood SERO and lung, multiple genes as tagged by the top 5 probes were involved in inflammation MESHD or antiviral immunity, and several other tagged genes, such as PON2 and HPS5, were involved in blood SERO blood MESHD coagulation. Conclusion: We identified IFNAR2 and other potential genes that could be involved in of the susceptibility or prognosis of COVID-19. These findings provide important leads to a better understanding of the mechanisms of cytokine storm and venous thromboembolism MESHD thromboembolism HP in COVID-19 and potential therapeutic target for effective treatment of COVID-19.

    Severity-stratified and longitudinal analysis of VWF/ADAMTS13 imbalance, altered fibrin crosslinking and inhibition of fibrinolysis as contributors to COVID-19 coagulopathy MESHD

    Authors: Kieron South; Lucy Roberts; Lucy Victoria Morris; Elizabeth Mann; Madhvi Menon; Sean Knight; Joanne E Konkel; Andrew Ustianowsk; Nawar D Bakerly; Paul M Dark; Angela Simpson; Timothy Felton; Alexander Horsley; - CIRCO; Tracy Hussell; John R. Grainger; Craig J Smith; Stuart M Allan; Michelle M. Lister; Hannah C. Howson-Wells; Edward C Holmes; Matthew W. Loose; Jonathan K. Ball; C. Patrick McClure; - The COVID-19 Genomics UK consortium study group; Shi Chen

    doi:10.1101/2020.08.18.20159608 Date: 2020-08-21 Source: medRxiv

    Background: Early clinical reports have suggested that the prevalence SERO of thrombotic complications MESHD in the pathogenesis of COVID-19 may be as high as 30% in intensive care unit (ICU)-admitted patients and could be a major factor contributing to mortality. However, mechanisms underlying COVID-19-associated thrombo-coagulopathy MESHD, and its impact on patient morbidity and mortality, are still poorly understood. Methods: We performed a comprehensive analysis of coagulation and thromboinflammatory factors in plasma SERO from COVID-19 patients with varying degrees of disease severity. Furthermore, we assessed the functional impact of these factors on clot formation and clot lysis. Results: Across all COVID-19 disease severities (mild, moderate and severe) we observed a significant increase (6-fold) in the concentration of ultra-large von Willebrand MESHD factor (UL-VWF) multimers compared to healthy controls. This is likely the result of an interleukin (IL)-6 driven imbalance of VWF and the regulatory protease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13). Upregulation of this key pro-coagulant pathway may also be influenced by the observed increase (~6-fold) in plasma SERO -defensins, a consequence of increased numbers of neutrophils and neutrophil activation. Markers of endothelial, platelet and leukocyte activation were accompanied by increased plasma SERO concentrations of Factor XIII (FXIII) and plasminogen activator inhibitor (PAI)-1. In patients with high FXIII we observed alteration of the fibrin network structure in in vitro assays of clot formation, which coupled with increased PAI-1, prolonged the time to clot lysis by the t-PA/plasmin fibrinolytic pathway by 52% across all COVID-19 patients (n=23). Conclusions: We show that an imbalance in the VWF/ADAMTS13 axis causing increased VWF reactivity may contribute to the formation of platelet-rich thrombi in the pulmonary vasculature of COVID-19 patients. Through immune and inflammatory responses, COVID-19 also alters the balance of factors involved in fibrin generation and fibrinolysis which accounts for the persistent fibrin deposition previously observed in post-mortem lung tissue.

    COVID-19 induces a hyperactive MESHD phenotype in circulating platelets

    Authors: Shane P Comer; Sarah Cullivan; Paulina B Szklanna; Luisa Weiss; Steven Cullen; Sarah Kelliher; Albert Smolenski; Niamh Moran; Claire Murphy; Haidar Altaie; John Curran; Katherine O'Reilly; Aoife G Cotter; Brian Marsh; Sean Gaine; Patrick Mallon; Brian McCullagh; Fionnuala Ní Áinle; Barry Kevane; Patricia B Maguire

    doi:10.1101/2020.07.24.20156240 Date: 2020-07-26 Source: medRxiv

    Background Coronavirus disease MESHD 2019 (COVID-19), caused by novel coronavirus SARS-CoV-2 MESHD, has to date affected over 13.3 million globally. Although high rates of venous thromboembolism MESHD thromboembolism HP and evidence of COVID-19-induced endothelial dysfunction have been reported, the precise aetiology of the increased thrombotic MESHD risk associated with COVID-19 infection MESHD remains to be fully elucidated. Objectives Here, we assessed clinical platelet parameters and circulating platelet activity in patients with severe and non-severe COVID-19. Methods An assessment of clinical blood SERO parameters in patients with severe COVID-19 disease MESHD (requiring intensive care), patients with non-severe disease (not requiring intensive care), general medical in-patients without COVID-19 and healthy donors was undertaken. Platelet function and activity were also assessed by secretion and specific marker analysis. Results We show that routine clinical blood SERO parameters including increased MPV and decreased platelet:neutrophil ratio are associated with disease severity in COVID-19 upon hospitalisation and intensive care unit admission. Strikingly, agonist-induced ADP release was dramatically higher in COVID-19 patients compared with non-COVID-19 hospitalized patients and circulating levels of PF4, sP-selectin and TPO were also significantly elevated in COVID-19. Conclusion Distinct differences exist in routine full blood SERO count and other clinical laboratory parameters between patients with severe and non-severe COVID-19. Moreover, we have determined that COVID-19 patients possess hyperactive circulating platelets. These data suggest that abnormal platelet reactivity may contribute to hypercoagulability HP hypercoagulability MESHD in COVID-19. Further investigation of platelet function in COVID-19 may provide additional insights into the aetiology of thrombotic risk in this disease and may contribute to the optimisation of thrombosis MESHD prevention and treatment strategies.

    Clinical Characteristics and Outcomes of Venous Thromboembolism MESHD Thromboembolism HP in Patients Hospitalized for COVID-19: Systematic Review and Meta-Analysis

    Authors: Joshua Henrina; Iwan Cahyo Santosa Putra; Irvan Cahyadi; Hoo Felicia Hadi Gunawan; Alius Cahyadi; Leonardo Paskah Suciadi

    doi:10.1101/2020.06.14.20130922 Date: 2020-06-16 Source: medRxiv

    Objective: To investigate the clinical characteristics and outcomes of Coronavirus Disease MESHD of 2019 (COVID-19) patients complicated with venous thromboembolism MESHD thromboembolism HP ( VTE MESHD) Method: We performed a comprehensive literature search of several databases to find studies that assessed VTE MESHD in hospitalized COVID-19 patients with a primary outcome of all-cause mortality and secondary outcomes of intensive care unit (ICU) admission and mechanical ventilation. We also evaluated the clinical characteristics of VTE MESHD sufferers. Objective: To investigate the clinical characteristics and outcomes of Coronavirus Disease MESHD of 2019 (COVID-19) patients complicated with venous thromboembolism MESHD thromboembolism HP ( VTE MESHD) Method: We performed a comprehensive literature search of several databases to find studies that assessed VTE MESHD in hospitalized COVID-19 patients with a primary outcome of all-cause mortality and secondary outcomes of intensive care unit (ICU) admission and mechanical ventilation. We also evaluated the clinical characteristics of VTE MESHD sufferers. Results: Eight studies have been included with a total of 1237 pooled subjects. Venous thromboembolism MESHD thromboembolism HP was associated with higher mortality (RR 2.48 (1.35, 4.55), p=0.003; I2 5%, p=0.35) after we performed sensitivity SERO analysis, ICU admission (RR 2.32 (1.53, 3.52), p<0.0001; I2 80%, p <0.0001), and mechanical ventilation need (RR 2.73 (1.56, 4.78), p=0.0004; I2 77%, p=0.001). Furthermore, it was also associated to male TRANS gender TRANS (RR 1.21 (1.08, 1.35), p=0.0007; I2 12%, p=0.34), higher white blood SERO cells count (MD 1.24 (0.08, 2.41), 0.04; I2 0%; 0.26), D-dimer (MD 4.49 (2.74, 6.25), p<0.00001; I2 67%, p=0.009) and LDH levels (MD 70.93 (19.33, 122.54), p<0.007; I2 21%, p=0.28). In addition, after sensitivity SERO analysis was conducted, VTE MESHD also associated with older age TRANS ( MD MESHD 2.79 (0.06, 5.53), p=0.05; I2 25%, p=0.24) and higher CRP levels (MD 2.57 (0.88, 4.26); p=0.003; I2 0%, p=0.96). Conclusion: Venous thromboembolism MESHD thromboembolism HP in COVID-19 patients was associated with increased mortality, ICU admission, and mechanical ventilation requirement. Male TRANS gender TRANS, older age TRANS, higher levels of biomarkers, including WBC count, D-Dimer, and LDH were also being considerably risks for developing VTE MESHD in COVID-19 patients during hospitalization. Conclusion: Venous thromboembolism MESHD thromboembolism HP in COVID-19 patients was associated with increased mortality, ICU admission, and mechanical ventilation requirement. Male TRANS gender TRANS, older age TRANS, higher levels of biomarkers, including WBC count, D-Dimer, and LDH were also being considerably risks for developing VTE MESHD in COVID-19 patients during hospitalization.

    High Incidence of Venous Thrombosis HP Venous Thrombosis MESHD in Patients with Moderate to Severe COVID-19

    Authors: Oleg B Kerbikov; Pavel Yu Orekhov; Ekaterina N Borskaya; Natalia S Nosenko

    doi:10.1101/2020.06.12.20129536 Date: 2020-06-14 Source: medRxiv

    COVID-19 predisposes to venous thromboembolism MESHD thromboembolism HP and there are multiple data regarding high incidence of venous thrombosis HP venous thrombosis MESHD in critical COVID-19 patients, however reports on this complication in less severe patients are not widely available. The aim of this study was to investigate the incidence of deep-vein thrombosis MESHD ( DVT MESHD) in patients with moderate to severe COVID-19 and to assess the prevalence SERO of DVT MESHD with lung computerized tomography (lung CT) exams, clinical information and lab data. This study examined 75 consecutive patients with moderate to severe COVID-19, with specific exclusions. METHODS Almost all patients (pts) admitted to our hospital in the first half of May underwent comprehensive vein ultrasonography. 75 pts ( aged TRANS 27-92 y, median - 63 y, 36 males TRANS and 39 females TRANS) with moderate to severe COVID-19 were included in our study. RESULTS Spontaneous echo contrast (decreased blood SERO velocity and blood SERO stasis) was detected in common femoral veins in 53 pts (70.7%). DVT MESHD was found in 15 pts (20%). The vast majority of those with DVT MESHD (13 pts, 86.7%) had thrombi only in calf veins and ileofemoral thrombosis MESHD was detected in 2 pts with DVT MESHD (13.3%). There was no significant observed difference between DVT MESHD and non- DVT MESHD patients with respect to age TRANS, underlying diseases, lung CT scores and SpaO2 at admission. There was also no significant observed difference between DVT MESHD and non- DVT MESHD patients with respect to both "time from symptoms onset TRANS to admission" and with respect to the majority of lab data. However, a significant difference was observed in D-dimer level (1.87 +/- 1.62 vs 0.51 +/- 0,4 mcg/mL p<0.0001) and C-reactive protein (116.9 +/- 83,6 and 65.1 +/- 64.98 mg/L, p = 0.014) for patients with DVT MESHD and patients without DVT MESHD respectably (Receiver operating characteristics (ROC) curve analysis revealed that the level of D-dimer >/= 0.69 mcg/mL is the predictor of DVT MESHD with a sensitivity SERO of 76.9%, a specificity of 77.6%, p < 0.001 (AUC area under curve = 0.7944). Logistic regression confirmed that D-dimer is an independent predictor of DVT MESHD and patients with D-dimer >/= 0.69 mcg/mL have odds ratio (OR) of developing DVT MESHD = 5.1 (confidence interval [CI] 1.9 - 13.5)). CONCLUSION Patients with moderate to severe COVID-19 show high incidence of DVT MESHD, indicating that moderate to severe COVID-19 patients may require an early administration of anticoagulation therapy as part of their treatment. Such therapy may be continued after hospital discharge. Based on these findings, these patients may also require a follow-up with vein ultrasonography after recovery to rule out DVT MESHD.

    Risk factors for clinical progression in patients with COVID-19: a retrospective study of electronic health record data in the United Kingdom

    Authors: Robert A Fletcher; Thomas Matcham; Marta Tibúrcio; Arseni Anisimovich; Stojan Jovanović; Luca Albergante; Nadezda Lipunova; Anne Hancock; Lucy Mackillop; Lionel Tarassenko; Alex McCarthy; Marcela P Vizcaychipi; Rabia Tahir Khan

    doi:10.1101/2020.05.11.20093096 Date: 2020-05-15 Source: medRxiv

    Background: The novel coronavirus disease MESHD 2019 (COVID-19) outbreak presents a significant threat to global health. A better understanding of patient clinical profiles is essential to drive efficient and timely health service strategies. In this study, we aimed to identify risk factors for a higher susceptibility to symptomatic presentation with COVID-19 and a transition to severe disease. Methods: We analysed data on 2756 patients admitted to Chelsea & Westminster Hospital NHS Foundation Trust between 1st January and 23rd April 2020. We compared differences in characteristics between patients designated positive for COVID-19 and patients designated negative on hospitalisation and derived a multivariable logistic regression model to identify risk factors for predicting risk of symptomatic COVID-19. For patients with COVID-19, we used univariable and multivariable logistic regression to identify risk factors associated with progression to severe disease defined by: 1) admission to the hospital AICU, 2) the need for mechanical ventilation, 3) in-hospital mortality, and 4) at least one measurement of elevated D-dimer (equal or superior to 1,000 ug/L) indicative of increased risk of venous thromboembolism MESHD thromboembolism HP. Results: The patient population consisted of 1148 COVID-19 positive and 1608 COVID-19 negative patients. Age TRANS, sex, self-reported ethnicity, C-reactive protein, white blood SERO cell count, respiratory rate, body temperature, and systolic blood SERO pressure formed the most parsimonious model for predicting risk of symptomatic COVID-19 at hospital admission. Among 1148 patients with COVID-19, 116 (10.1%) were admitted to the AICU, 71 (6.2%) required mechanical ventilation, 368 (32.1%) had at least one record of D-dimer levels [≥]1,000 g/L, and 118 patients died. In the multivariable logistic regression, age TRANS (OR = 0.953 per 1 year, 95% CI: 0.937-0.968) C-reactive protein (OR = 1.004 per 1 mg/L, 95% CI: 1.002-1.007), and white blood SERO cell counts (OR = 1.059 per 109/L, 95% CI: 1.010-1.111) were found to be associated with admission to the AICU. Age TRANS (OR = 0.973 per 1 year, 95% CI: 0.955-0.990), C-reactive protein (OR = 1.003 per 1 mg/L, 95% CI: 1.000-1.006) and sodium (OR = 0.915 per 1 mmol/L, 0.868-0.962) were associated with mechanical ventilation. Age TRANS (OR = 1.023 per 1 year, 95% CI: 1.004-1.043), CRP (OR = 1.004 per 1 mg/L, 95% CI: 1.002-1.006), and body temperature (OR = 0.723 per 1oC, 95% CI: 0.541-0.958) were associated with elevated D-dimer. For mortality, we observed associations with age TRANS (OR = 1.060 per 1 year, 95% CI: 1.040-1.082), female TRANS sex (OR = 0.442, 95% CI: 0.442, 95% CI: 0.245-0.777), Asian ethnic background (OR = 2.237 vs White ethnic background, 95% CI: 1.111-4.510), C-reactive protein (OR = 1.004 per 1 mg/L, 95% CI: 1.001-1.006), sodium (OR = 1.038 per 1 mmol/L, 95% CI: 1.001-1.006), and respiratory rate (OR = 1.054 per 1 breath MESHD/min, 95% CI: 1.024-1.087). Conclusion: Our analysis suggests there are several demographic, clinical and laboratory findings associated with a symptomatic presentation of COVID-19. Moreover, significant associations between patient deterioration were found with age TRANS, sex and specific blood SERO markers, chiefly C-reactive protein, and could help early identification of patients at risk of poorer prognosis. Further work is required to clarify the extent to which our observations are relevant beyond current settings.

    Neutrophil extracellular traps and thrombosis MESHD in COVID-19

    Authors: Yu Zuo; Melanie Zuo; Srilakshmi Yalavarthi; Kelsey Gockman; Jacqueline A. Madison; Hui Shi; Wrenn Woodard; Sean P. Lezak; Njira L. Lugogo; Jason S. Knight; Yogendra Kanthi

    doi:10.1101/2020.04.30.20086736 Date: 2020-05-05 Source: medRxiv

    Background: Early studies of patients with COVID-19 have demonstrated markedly dysregulated coagulation MESHD and a high risk of morbid arterial and venous thrombotic MESHD events. While elevated levels of blood SERO neutrophils and neutrophil extracellular traps (NETs) have been described in patients with COVID-19, their potential role in COVID-19-associated thrombosis MESHD remains unknown. Objectives: To elucidate the potential role of hyperactive neutrophils and NET release in COVID-19-associated thrombosis MESHD. Patients/Methods: This is a retrospective, case-control study of patients hospitalized with COVID-19 who developed thrombosis MESHD (n=11), as compared with gender TRANS- and age TRANS-matched COVID-19 patients without clinical thrombosis MESHD (n=33). In addition to capturing clinical data, we measured remnants of NETs (cell-free DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3) and neutrophil-derived S100A8/A9 (calprotectin) in patient sera. Results: The majority of patients (9/11) were receiving at least prophylactic doses of heparinoids at the time thrombosis MESHD was diagnosed. As compared with controls, patients with COVID-19-associated thrombosis MESHD had significantly higher blood SERO levels of markers of NETs (cell-free DNA, myeloperoxidase-DNA complexes, citrullinated histone H3) and neutrophil activation (calprotectin). The thrombosis MESHD group also had higher levels of D-dimer, CRP, ferritin, and platelets, but not troponin or neutrophils. Finally, there were strong associations between markers of hyperactive neutrophils (calprotectin and cell-free DNA) and D-dimer. Conclusion: Elevated levels of neutrophil activation and NET formation in patients hospitalized with COVID-19 are associated with higher risk of morbid thrombotic complications MESHD. These observations underscore the need for urgent investigation into the potential relationship between NETs and unrelenting thrombosis MESHD in COVID-19.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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