Corpus overview


MeSH Disease

Human Phenotype


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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.

    Comparative analysis of immune-associated genes in COVID-19, cardiomyopathy HP cardiomyopathy MESHD and venous thromboembolism MESHD thromboembolism HP

    Authors: Grant E Castaneda; Abby C Lee; Wei Tse Li; Chengyu Chen; Jaideep Chakladar; Eric Chang; Weg Ongkeko; Xiaojian Liu; Wei Gao; Renli Zhang; Qiru Su; Andrew Azman; Justin Lessler; Xuan Zou; Wenfeng Gong; Brenda Clemente; Jerel Vega; Scott Roberts; Jose A. Gonzalez; Marciano Sablad; Rodrigo Yelin; Wendy Taylor; Kiyoshi Tachikawa; Suezanne Parker; Priya Karmali; Jared Davis; Sean M Sullivan; Steve G. Hughes; Pad Chivukula; Eng Eong Ooi

    doi:10.1101/2020.08.28.20184234 Date: 2020-09-02 Source: medRxiv

    As of 28 August 2020, there have been 5.88 million Coronavirus Disease MESHD 2019 (COVID-19) cases and 181,000 COVID-19 related deaths in the United States alone. Given the lack of an effective pharmaceutical treatment for COVID-19, the high contagiousness of the disease and its varied clinical outcomes, identifying patients at risk of progressing to severe disease is crucial for the allocation of valuable healthcare resources during this pandemic. Current research has shown that there is a higher prevalence SERO of cardiovascular comorbidities amongst patients with severe COVID-19 or COVID-19-related deaths, but the link between cardiovascular disease MESHD and poorer prognosis is poorly understood. We believe that pre-existing immune dysregulation HP that accompanies cardiovascular disease MESHD predisposes patients to a harmful inflammatory immune response, leading to their higher risk of severe disease. Thus, in this project, we aim to characterize immune dysregulation HP dysregulation MESHD in patients with cardiomyopathy HP cardiomyopathy MESHD, venous thromboembolism MESHD thromboembolism HP and COVID-19 patients by looking at immune-associated gene dysregulation, immune HP infiltration and dysregulated immunological pathways and gene signatures.

    Epidemiology of Venous Thromboembolism MESHD Thromboembolism HP in SARS- CoV-2 Infected MESHD Patients: A Systematic Review and Meta-Analysis

    Authors: Souvik Maitra; Dalim Kumar Baidya; Sulagna Bhattacharjee; Rahul Kumar Anand; Bikash Ranjan Ray; A. Christine Argento; Michelle H. Prickett; - NU COVID Investigators; Richard G. Wunderink; Sean B. Smith; Samira Mubareka; Allison McGeer; Adrienne K Chan; Anne-Claude Gingras; Tania H Watts; Mario Ostrowski; Elisabet Leiva; Albert Ariza-Sole; Paolo D Dallaglio; Maria Quero; Antonio Soriano; Alberto Pasqualetto; Maylin Koo; Virginia Esteve; Arnau Antoli; Rafael Moreno; Sergi Yun; Pau Cerda; Mariona Llaberia; Francesc Formiga; Marta Fanlo; Abelardo Montero; David Chivite; Olga Capdevila; Ferran Bolao; Xavier Pinto; Josep Llop; Antoni Sabate; Jordi Guardiola; Josep M Cruzado; Josep Comin-Colet; Salud Santos; Ramon Jodar; Xavier Corbella

    doi:10.1101/2020.08.28.20184028 Date: 2020-09-01 Source: medRxiv

    Early reports from China and Europe indicated that incidence of venous thromboembolism MESHD thromboembolism HP in COVID-19 patients may be high. In this meta-analysis of observational studies was designed to know worldwide prevalence SERO of thromboembolic MESHD events in COVID-19 patients. Primary outcome of our review was to assess the proportion of patients with VTE MESHD. Secondary outcomes were to assess the proportion of patients with DVT and proportion of patients with PE. Random effect meta-analysis model with restricted maximum likelihood estimator was used for all analysis. Pooled proportion with 95% confidence interval (95% CI) and heterogeneity (I2) was reported for all outcomes. Data of 5426 patients from n=19 articles were included in this systematic review and meta-analysis. Incidence of VTE MESHD (95% CI), PE (95% CI) and DVT (95% CI) was 23 (10- 36) %, 12 (6- 17) % and 15 (8- 23) %. We have found a high but incidence of thromboembolic MESHD events in COVID-19 patients. Further well-designed studies are required in this area to identify true incidence and risk factors of it.

    Incidence of thromboembolism HP thromboembolism MESHD in patients with COVID-19: a systematic review and meta-analysis

    Authors: Kochawan Boonyawat; Pichika Chantrathammachart; Pawin Numthavej; Nithita Nanthatanti; Sithakom Phusanti; Angsana Phuphuakrat; Pimjai Niparuck; Pantep Angchaisuksiri

    doi:10.21203/ Date: 2020-08-21 Source: ResearchSquare

    Background Since the beginning of the coronavirus disease MESHD 2019 (COVID-19) pandemic, the incidence of thromboembolism HP thromboembolism MESHD has been increasingly reported. The aim of this systematic review was to explore the incidence of venous and arterial thromboembolism MESHD thromboembolism HP among COVID-19 patients requiring hospitalization.Methods Medline, Embase, Scopus, and grey literature were searched until May 2020. Observational studies reported on the incidence of venous thromboembolism MESHD thromboembolism HP ( VTE MESHD), including pulmonary embolism HP pulmonary embolism MESHD ( PE MESHD) and deep vein thrombosis MESHD ( DVT MESHD) or arterial thromboembolism MESHD thromboembolism HP ( ATE MESHD) were included. The pool incidences and their 95% confidence intervals (CI) were calculated using the random-effects model.Results A total of 26 studies were included. In the intensive care unit (ICU) setting, the pooled incidence of VTE MESHD was 27% (95% CI, 20–35%). Subgroups based on compression ultrasound (CUS) screening revealed a higher incidence of DVT MESHD in the CUS screening group than in the no CUS screening group (27% [95% CI, 20–35%] vs. 3% [95% CI, 1–5%]). The pooled incidence of ATE MESHD in ICU was 3% (95% CI, 2–4%). In the non-ICU setting, the pooled incidence of VTE MESHD was 8% (95% CI, 4–12%,).Conclusions The incidence of VTE MESHD in COVID-19 patients was higher in the ICU setting than in the non-ICU setting, and also significantly higher in studies that incorporated the CUS screening protocol. The incidence of ATE MESHD in the ICU setting was low. VTE MESHD prophylactic measures should be given to all hospitalized patients diagnosed with COVID-19, especially in the ICU setting.

    D-dimers at hospital admission for COVID-19 are associated with in hospital mortality independently of venous thromboembolism MESHD thromboembolism HP: Insight from a French multicenter cohort study

    Authors: Richard Chocron; Baptiste Duceau; Nicolas Gendron; Nacim Ezzouhairi; Lina Khider; Antonin Trimaille; Guillaume Goudot; Orianne Weizman; Jean Marc Alsac; Thibault Pommier; Olivier Bory; Joffrey Cellier; Aurélien Philippe; Laura Geneste; Iannis Ben Abdallah; Vassili Panagides; Salma El Batti; Wassima Marsou; Philippe Juvin; Antoine Deney; Emmanuel Messas; Sabir Attou; Benjamin Planquette; Delphine Mika; Pascale Gaussem; Charles Fauvel; Jean-Luc Diehl; Theo Pezel; Tristan Mirault; Willy Sutter; Olivier Sanchez; Guillaume Bonnet; Ariel Cohen; David M. Smadja

    doi:10.21203/ Date: 2020-08-19 Source: ResearchSquare

    Background: Coronavirus disease 2019 (COVID-19) has been associated with coagulation disorders MESHD, in particular high levels of D-dimers, and increased frequency of venous thromboembolism MESHD thromboembolism HP ( VTE MESHD). We explore the association between D-dimers at admission and in-hospital mortality in hospitalized COVID-19 patients with or without symptomatic VTE MESHD.Methods: From February 26 to April 20, 2020, D-dimer level at admission and outcomes of patients hospitalized for COVID-19 in medical wards (in-hospital mortality or VTE MESHD) were retrospectively analyzed in a multicenter study in 24 French hospitals.Results: Among 2878 patients enrolled in the study, 1154 (40.9%) patients had D-dimer measurement at admission. A receiver operating characteristic (ROC) curve analysis identified D-dimer level above 1128 ng/mL as the optimum cutoff value to predict in-hospital mortality (Area Under the Curve of 64.9% (95% CI 0.60–0.69) with a sensitivity SERO of 71.1% (95% CI 0.62–0.78) and a specificity of 55.6% (95% CI 0.52–0.58) that not differ in the subgroup of patients with VTE during hospitalization. Among 609 (52.8%) patients with D-dimers level < 1128 ng/mL at admission, only 35 (5.7%) deaths occurred during hospitalization. After adjustment, in a cox proportional hazard and logistic regression models, D-dimers above 1128 ng/mL at admission were also associated to a worth prognosis with a OR of 3.07 (95% CI 2.05–4.69, p < 0.001) and an unadjusted hazard ratio of 2.11 (95%CI 1.31–3.4, p < 0.01).Conclusions: D-dimer level over 1128 ng/mL is a relevant predictive factor for in-hospital mortality in COVID-19 hospitalized patients in medical ward, regardless the occurrence of VTE during hospitalization.

    High Incidence of Venous Thromboembolism MESHD Thromboembolism HP in Patients with Coronavirus Disease MESHD 2019: A Call for Improved Awareness and Prevention

    Authors: Yun-xia Zhang; Meng Zhang; Yimin Wang; Wei Qin; Zhu Zhang; Chenghong Li; Zhenguo Zhai

    doi:10.21203/ Date: 2020-08-16 Source: ResearchSquare

    Background: An increased risk of venous thromboembolism MESHD thromboembolism HP ( VTE MESHD) in patients with coronavirus disease MESHD 2019 (COVID-19) has been reported. We performed a meta-analysis to evaluate the prevalence SERO of VTE MESHD in COVID-19 patients.Methods: The PubMed and Embase databases were searched for studies reporting VTE MESHD in COVID-19 patients up to June 27, 2020. The selected studies were predefined into the “suspected screening group” and the “routine screening group.” The VTE MESHD prevalence SERO was calculated using random-effect models.Results: We selected 20 studies including a total of 2763 COVID-19 patients. In 2203 COVID-19 patients from the suspected screening group, the pool VTE MESHD incidence was 15.2% (95% confidence interval [CI]: 10.5–21.6%). In 560 COVID-19 patients from the routine screening group, the VTE MESHD prevalence SERO was 40.8% (95% CI: 20.6–64.7%). Furthermore, the VTE MESHD incidence of critically ill COVID-19 patients from the two groups was 19.6% and 61.4%, respectively, which indicates that critically ill COVID-19 patients were more susceptible to VTE MESHD.Conclusions: A high incidence of VTE MESHD was observed in COVID-19 patients, especially in severe cases. The incidence of VTE MESHD in COVID-19 patients from the routine screening group was higher than that in patients from the suspected screening group. This indicates that a lower threshold of suspicion to perform VTE MESHD imaging tests may be reasonable and there is an urgent need to adapt a regular screening strategy for VTE MESHD.

    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.

    The 4C Initiative (Clinical Care for Cardiovascular disease MESHD in the COVID-19 pandemic): monitoring the indirect impact of the coronavirus pandemic on services for cardiovascular diseases MESHD in the UK

    Authors: - TC CVD-COVID-UK Consortium; Simon Ball; Amitava Banerjee; Colin Berry; Jonathan Boyle; Benjamin Bray; William Bradlow; Afzal Chaudhry; Rikki Crawley; John Danesh; Alastair Denniston; Florian Falter; Jonine Figueroa; Christopher Hall; Harry Hemingway; Emily Jefferson; Tom Johnson; Graham King; Ken Lee; Paul McKean; Suzanne Mason; Nicholas Mills; Ewen Pearson; Munir Pirmohamed; Michael TC Poon; Rouven Priedon; Anoop Shah; Reecha Sofat; Jonathan Sterne; Fiona Strachan; Cathie LM Sudlow; Zsolt Szarka; William Whiteley; Mike Wyatt

    doi:10.1101/2020.07.10.20151118 Date: 2020-07-11 Source: medRxiv

    Background: The coronavirus (COVID-19) pandemic affects cardiovascular diseases MESHD ( CVDs MESHD) directly through infection MESHD and indirectly through health service reorganisation and public health policy. Real-time data are needed to quantify direct and indirect effects. We aimed to monitor hospital activity for presentation, diagnosis and treatment of CVDs MESHD during the pandemic to inform on indirect effects. Methods: We analysed aggregate data on presentations, diagnoses and treatments or procedures for selected CVDs MESHD (acute coronary syndromes, heart failure MESHD, stroke HP stroke MESHD and transient ischaemic attack MESHD, venous thromboembolism MESHD thromboembolism HP, peripheral arterial disease MESHD and aortic aneurysm HP aortic aneurysm MESHD) in UK hospitals before and during the COVID-19 epidemic. We produced an online visualisation tool to enable near real-time monitoring of trends. Findings: Nine hospitals across England and Scotland contributed hospital activity data from 28 Oct 2019 (pre-COVID-19) to 10 May 2020 (pre-easing of lockdown), and for the same weeks during 2018-2019. Across all hospitals, total admissions and emergency department (ED) attendances decreased after lockdown (23 March 2020) by 57.9% (57.1-58.6%) and 52.9% (52.2-53.5%) respectively compared with the previous year. Activity for cardiac, cerebrovascular and other vascular conditions started to decline 1-2 weeks before lockdown, and fell HP by 31-88% after lockdown, with the greatest reductions observed for coronary artery bypass grafts, carotid endarterectomy, aortic aneurysm HP aortic aneurysm MESHD repair and peripheral arterial disease MESHD procedures. Compared with before the first UK COVID-19 (31 January 2020), activity declined across diseases and specialties between the first case and lockdown (total ED attendances RR 0.94, 0.93-0.95; total hospital admissions RR 0.96, 0.95-0.97) and after lockdown (attendances RR 0.63, 0.62-0.64; admissions RR 0.59, 0.57-0.60). There was limited recovery towards usual levels of some activities from mid-April 2020. Interpretation: Substantial reductions in total and cardiovascular activities are likely to contribute to a major burden of indirect effects of the pandemic, suggesting they should be monitored and mitigated urgently.

    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.

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MeSH Disease
Human Phenotype

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