Corpus overview


MeSH Disease

Human Phenotype


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    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.

    Association of D-dimer and fibrinogen magnitude with hypercoagulability HP hypercoagulability MESHD by thromboelastography in severe COVID-19

    Authors: Abhimanyu Chandel; Saloni Patolia; Mary Looby; Heidi Dalton; Najeebah Bade; Vikramjit Khangoora; Mehul Desai; James Lantry; Erik Osborn; Svetolik Djurkovic; Daniel Tang; Steven D Nathan; Christopher S King

    doi:10.1101/2020.07.27.20162842 Date: 2020-07-29 Source: medRxiv

    Introduction: D-dimer concentration has been used to identify candidates for intensified anticoagulant treatment for both venous thromboembolism MESHD thromboembolism HP prevention and mitigation of the microthrombotic complications MESHD associated with COVID-19. Thromboelastography (TEG) maximum amplitude (MA) has been validated as an indicator of hypercoagulability HP hypercoagulability MESHD and MA [≥] 68 mm has been utilized as a marker of hypercoagulability HP hypercoagulability MESHD in other conditions. We evaluated the relationship between coagulation, inflammatory, and TEG parameters in patients with COVID-19 on extracorporeal membrane oxygenation (ECMO). Methods: We performed a single center retrospective analysis of consecutive patients that received ECMO for the treatment of COVID-19. TEG, inflammatory, and coagulation markers were compared in patients with and without thrombotic complications MESHD. Correlation tests were performed to identify the coagulation and inflammatory markers that best predict hypercoagulability HP hypercoagulability MESHD as defined by an elevated TEG MA. Results: 168 TEGs were available in 24 patients. C-reactive protein and fibrinogen were significantly higher in patients that developed a thrombotic MESHD event versus those that did not (p=0.038 and p=0.043 respectively). D-dimer was negatively correlated with TEG MA (p<0.001) while fibrinogen was positively correlated (p<0.001). A fibrinogen > 441 mg/dL had a sensitivity SERO of 91.2% and specificity of 85.7% for the detection of MA [≥] 68 mm. Conclusions: In critically ill MESHD patients with COVID-19, D-dimer concentration had an inverse relationship with hypercoagulability HP hypercoagulability MESHD as measured by TEG MA. D-dimer elevation may reflect severity of COVID-19 related sepsis HP sepsis MESHD rather than designate patients likely to benefit from anticoagulation. Fibrinogen concentration may represent a more useful marker of hypercoagulability HP hypercoagulability MESHD in this population.

    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.

    Tocilizumab and Thromboembolism HP Thromboembolism MESHD in COVID-19: A Retrospective Hospital-based Cohort Analysis

    Authors: Kok Hoe Chan; Bhavik Patel; Bishnu Podel; Maria E Szabela; Hamid S Shaaban; Gunwant Guron; Jihad Slim

    doi:10.21203/ Date: 2020-07-02 Source: ResearchSquare

    Background:Tocilizumab, an IL-6 receptor antagonist has been used in patients with Coronavirus Disease MESHD 2019 (COVID-19) as an anti-cytokine agent. IL-6 also plays a complex role in hemostasis and thrombosis MESHD. We observed a transient elevation of D-dimer in our patients who received Tocilizumab, which triggered the current study.Methods:A retrospective hospital-based cohort analysis of patients with confirmed COVID-19 who received Tocilizumab during the study period of 03/15/2020 to 05/20/2020. We retrieved demographic, clinical and laboratory data, we excluded patients who were receiving therapeutic anticoagulation therapy prior to Tocilizumab administration.  Descriptive analysis was performed, the cause of death MESHD and trends of D-dimer and inflammatory markers were studied. Results: Out of the 436 confirmed COVID 19 patients admitted during the study period, 24 met the inclusion criteria. Their median age TRANS was 47.5 years old. They were 18 males TRANS and 6 females TRANS; 15 patients survived, and 9 expired. Of the group that survived, 12 received therapeutic anticoagulation. Of the 7 patients who did not receive therapeutic anticoagulation, 4 expired, 1 from sepsis HP sepsis MESHD and 3 probably from thromboembolic complications MESHD, compared to 5 deaths in the 17 patients who received therapeutic anticoagulation with 4 dying from sepsis HP sepsis MESHD, and one possibly from thromboembolic complications MESHD.Conclusions:The interplay between IL-6, IL-6 receptor antagonist and venous thromboembolism MESHD thromboembolism HP are complex. We observed a transient elevation of D-dimer in COVID-19 patients who received Tocilizumab, and a trend toward increased death secondary to thromboembolism HP thromboembolism MESHD. This observation is novel and highlights the potential thrombophilic side effects of Tocilizumab.

    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.

    Aortic Thrombus MESHD in patients with Severe Covid-19. Review of three cases

    Authors: Maria Carranza; Danilo Salazar; Jesús Troya; Roberto Alcazar; Cristina Peña; Nuria Muñoz

    doi:10.21203/ Date: 2020-05-12 Source: ResearchSquare

    Coronavirus disease MESHD 2019 (COVID-19) is suspected to predispose to both venous and arterial thromboembolism MESHD thromboembolism HP, in the context of an exaggerated immune response to the virus, especially in severe patients. Even though aortic thrombi MESHD are a rare entity, the new COVID-19 establishes the need to include them in the diagnosis, especially in patients with severe disease and no clinical improvement. Herein, we describe a series of three cases of aortic thrombi MESHD diagnosed by computerized tomography (CT) angiography in patients with confirmed SARS CoV-2 infection MESHD.

    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.

    Incidence of Venous Thromboembolism MESHD Thromboembolism HP in Hospitalized Patients with COVID-19

    Authors: Saskia Middeldorp; Michiel Coppens; Thijs F. van Haaps; Merijn Foppen; Alexander P. Vlaar; Marcella C.A. Muller; Catherine C.S. Bouman; Ludo F.M. Beenen; Ruud S. Kootte; Jarom Heijmans; Loek P. Smits; Peter I. Bonta; Nick van Es

    id:10.20944/preprints202004.0345.v1 Date: 2020-04-19 Source:

    Coronavirus disease MESHD 2019 (COVID-19) can lead to systemic coagulation activation and thrombotic complications MESHD. We investigated the incidence of objectively confirmed venous thromboembolism MESHD thromboembolism HP ( VTE MESHD) in 198 hospitalized patients with COVID-19 in a single-center cohort study. Seventy-four patients (37%) were admitted to the intensive care unit (ICU). At time of data collection, 58 (29%) were still hospitalized and 14% had died. During a median follow-up of 5 days (IQR, 3-9), 33 patients (17%) were diagnosed with VTE MESHD of whom 22 (11%) had symptomatic VTE MESHD, despite routine thrombosis MESHD prophylaxis. The cumulative incidences of VTE MESHD at 7 and 14 days were 15% (95% CI, 9.3-22) and 34% (95% CI, 23-46), respectively. For symptomatic VTE MESHD, these were 11% (95% CI, 5.8-17) and 23% (95% CI, 14-33). VTE MESHD appeared to be associated with death MESHD (adjusted HR, 2.9; 95% CI, 1.02-8.0). The cumulative incidence of VTE MESHD was higher in the ICU (25% at 7 days 95% CI, 15-36, and 48% at 14 days, 95% CI, 33-61) than on the wards (any VTE MESHD and symptomatic VTE MESHD 6.5 % at 7 days (95% CI, 1.5-17) and 10% at 14 days (95% CI, 2.9-24)).The observed risk for VTE MESHD in COVID-19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE. Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE MESHD and potentially improve survival.

    Risk assessment of venous thromboembolism MESHD thromboembolism HP and bleeding MESHD in COVID-19 patients

    Authors: Jin-fu Xu; Lan Wang; Lan Zhao; Feng Li; Ji Liu; Li Zhang; Qiuhong Li; Jin Gu; Suo Liang; Qinhua Zhao; Jinmin Liu

    doi:10.21203/ Date: 2020-03-20 Source: ResearchSquare

    Background The coronavirus disease MESHD 2019 (COVID-19) is a newly recognized illness that has spread rapidly all over the world. Severe hypoxemic respiratory failure MESHD respiratory failure HP from COVID-19 will bring high risk of venous thromboembolism MESHD thromboembolism HP ( VTE MESHD). Our study aims to identify in-hospital VTE MESHD risk and bleeding risk in COVID-19 patients. Methods We retrospectively studied 138 consecutively enrolled patients with COVID-19 and identified in-hospital VTE MESHD and bleeding risk by Padua Prediction Score and Improve bleed risk assessment model. The clinical data and features were analyzed in VTE MESHD patients. Results Our findings identified that 23 (16.67%) patients with COVID-19 were at high risk for VTE MESHD according to Padua prediction score, and 9(6.52%) patients were at high risk of bleeding MESHD for VTE MESHD prophylaxis according to Improve prediction score. Fifteen critically ill MESHD patients faced double high risk from thrombosis MESHD (Padua score more than 4 points in all 15[100%] patients) and hemorrhage MESHD (Improve score more than 7 points in 9[60.0%] patients). Thrombotic MESHD events were identified in four patients (2.9%) of all COVID-19 patients. All of them were diagnosed as deep vein thrombosis MESHD by ultrasound after 3 to 18 days after admission. Three (75.0%) were critically ill patients, which means the incidence of VTE MESHD among critically ill patients was 20%. One major hemorrhage MESHD was happened in critically ill MESHD patients during VTE MESHD treatment. Conclusion Critically ill MESHD patients with COVID-19 suffered both high risk of thrombosis MESHD and bleeding MESHD risks. More effective VTE MESHD prevention strategies based on an individual assessment of bleeding risks were necessary for critically ill patients with COVID-19.

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MeSH Disease
Human Phenotype

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