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SARS-CoV-2 proteins

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    Patient characteristics and predictors of mortality in 470 adults admitted to a district general hospital in England with Covid-19 MESHD

    Authors: Joseph V Thompson; Nevan Meghani; Bethan M Powell; Ian Newell; Roanna Craven; Gemma Skilton; Lydia J Bagg; Irha Yaqoob; Michael J Dixon; Eleanor J Evans; Belina Kambele; Asif Rehman; Georges Ng Man Kwong

    doi:10.1101/2020.07.21.20153650 Date: 2020-07-27 Source: medRxiv

    Background Understanding risk factors for death MESHD in Covid 19 is key to providing good quality clinical care. Due to a paucity of robust evidence, we sought to assess the presenting characteristics of patients with Covid 19 and investigate factors associated with death MESHD. Methods Retrospective analysis of adults admitted with Covid 19 to Royal Oldham Hospital, UK. Logistic regression modelling was utilised to explore factors predicting death. Results 470 patients were admitted, of whom 169 (36%) died. The median age was 71 years (IQR 57 to 82), and 255 (54.3%) were men. The most common comorbidities were hypertension MESHD (n=218, 46.4%), diabetes MESHD (n=143, 30.4%) and chronic neurological disease MESHD (n=123, 26.1%). The most frequent complications were acute kidney injury MESHD (n=157, 33.4%) and myocardial injury MESHD (n=21, 4.5%). Forty three (9.1%) patients required intubation and ventilation, and 39 (8.3%) received non-invasive ventilation Independent risk factors for death MESHD were increasing age (OR per 10 year increase above 40 years 1.87, 95% CI 1.57 to 2.27), hypertension MESHD (OR 1.72, 1.10 to 2.70), cancer MESHD (OR 2.20, 1.27 to 3.81), platelets <150x103/microlitre (OR 1.93, 1.13 to 3.30), C-reactive protein HGNC >100 micrograms/mL (OR 1.68, 1.05 to 2.68), >50% chest radiograph infiltrates, (OR 2.09, 1.16 to 3.77) and acute kidney injury MESHD (OR 2.60, 1.64 to 4.13). There was no independent association between death MESHD and gender, ethnicity, deprivation level, fever MESHD, SpO2/FiO2 (oxygen saturation index), lymphopenia MESHD or other comorbidities. Conclusions We characterised the first wave of patients with Covid 19 in one of Englands highest incidence areas, determining which factors predict death. These findings will inform clinical and shared decision making, including the use of respiratory support and therapeutic agents.

    The Pathogenisis of COVID-19 MESHD Myocardial Injury: an Immunohistochemical Study of Postmortem Biopsies 

    Authors: Camila Hartmann; Anna Flavia dos Santos Miggiolaro; Jarbas da Silva Motta Junior; Lucas Baena Carstens; Caroline Busatta Vaz De Paula; Sarah Fagundes Grobe; Larissa Hermann de Souza Nunes; Gustavo Lenci Marques; Lidia Zytynski Moura; Lucia de Noronha; Cristina Pellegrino Baena

    doi:10.21203/rs.3.rs-45192/v2 Date: 2020-07-17 Source: ResearchSquare

    Rationale: M yocardial injury MESHDis significantly and independently associated with mortality in COVID-19 MESHD patients. However, the pathogenesis of m yocardial injury MESHDin COVID-19 MESHD is still not clear, and cardiac involvement by SARS-CoV-2 remains a major challenge worldwide. Objective: This histopathological and immunohistochemical study seeks to clarify the pathogenesis and propose a mechanism with pathways involved in COVID-19 MESHD m yocardial injury. MESHD Methods and Results: Postmortem minimally invasive autopsies were performed in six patients who died from COVID-19 MESHD, and the myocardium samples were compared to a control patient. Histopathological analysis was performed using hematoxylin-eosin and toluidine blue staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against the following targets: c aspase-1, HGNC I CAM-1, HGNC T NF-α, HGNC I L-4, HGNC I L-6, HGNC C D163, HGNC T GF-β, HGNC M MP-9, HGNC type 1 and type 3 collagen. The samples were also subjected to a TUNEL assay to detect potential apoptosis. The histopathological analysis showed severe pericellular interstitial e dema MESHDsurrounding each of the cardiomyocytes and higher mast cells count by high-power field in all COVID-19 MESHD myocardium samples. The IHC analysis showed increased expression of c aspase-1, HGNC I CAM-1, HGNC I L-4, HGNC I L-6, HGNC C D163, HGNC M MP-9 HGNCand type 3 collagen in the COVID-19 MESHD patients compared to the control. No difference from the control was observed in expression of T NF-α, HGNC T GF-β HGNCand type 1 collagen. The TUNEL assay was positive in all the COVID-19 MESHD samples confirming the presence of endothelial apoptosis. Conclusions: The pathogenesis of COVID-19 MESHD m yocardial injury MESHDseems to be related with pyroptosis leading to endothelial cell injury and disfunction. The subsequent i nflammation MESHDwith associated interstitial e dema MESHDcould explain the myocardial disfunction and a rrythmias MESHDin these patients. Our findings also show that COVID-19 MESHD m yocardial injury MESHDmay cause m yocardial fibrosis MESHDin the long term. These patients should be monitored for m yocardial dysfunction MESHDand a rrythmias MESHDafter the acute phase of COVID-19 MESHD.

    Predicting COVID-19 MESHD Disease Progression and Patient Outcomes based on Temporal Deep Learning

    Authors: Chenxi Sun; Shenda Hong; Moxian Song; Hongyan Li; Zhenjie Wang

    doi:10.21203/rs.3.rs-44308/v4 Date: 2020-07-16 Source: ResearchSquare

    Background: The coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic has caused health concerns worldwide since December 2019. From the beginning of infection, patients will progress through different symptom stages, such as fever MESHD, dyspnea MESHD or even death. Identifying disease progression and predicting patient outcome at an early stage helps target treatment and resource allocation. However, there is no clear COVID-19 MESHD stage definition, and few studies have addressed characterizing COVID-19 MESHD progression, making the need for this study evident.Methods: We proposed a temporal deep learning method, based on a time-aware long short-term memory (T-LSTM) neural network and used an online open dataset, including blood samples of 485 patients from Wuhan, China, to train the model. Our method can grasp the dynamic relations in irregularly sampled time series, which is ignored by existing works. Specifically, our method predicted the outcome of COVID-19 MESHD patients by considering both the biomarkers and the irregular time intervals. Then, we used the patient representations, extracted from T-LSTM units, to subtype the patient stages and describe the disease progression of COVID-19 MESHD.Results: Using our method, the accuracy of the outcome of prediction results was more than 90% at 12 days and 98%, 95% and 93% at 3, 6, and 9 days, respectively. Most importantly, we found 4 stages of COVID-19 MESHD progression with different patient statuses and mortality risks. We ranked 40 biomarkers related to disease and gave the reference values of them for each stage. Top 5 is Lymph, LDH, hs-CRP, Indirect Bilirubin, Creatinine. Besides, we have found 3 complications - myocardial injury MESHD, liver function injury and renal function injury MESHD. Predicting which of the 4 stages the patient is currently in can help doctors better assess and cure the patient. Conclusions: To combat the COVID-19 MESHD epidemic, this paper aims to help clinicians better assess and treat infected MESHD patients, provide relevant researchers with potential disease progression patterns, and enable more effective use of medical resources. Our method predicted patient outcomes with high accuracy and identified a four-stage disease progression. We hope that the obtained results and patterns will aid in fighting the disease.

    Immunophenotyping of Circulating Leukocytes Reveal Non-specific Activation of Innate and Adaptive Immune Systems in Multi-System Inflammatory Syndrome of Childhood Temporally Associated with SARS-Cov-2 Infection MESHD: Descriptive Cohort Study

    Authors: Michael J. Carter; Matthew Fish; Aislinn Jennings; Katie J. Doores; Paul Wellman; Jeffrey Seow; Sam Acors; Emma Timms; Julia Kenny; Stuart Neil; Michael H. Malim; Shane M. Tibby; Manu Shankar-Hari

    id:10.20944/preprints202007.0252.v1 Date: 2020-07-12 Source: Preprints.org

    We describe the innate and adaptive immune system trajectory in Multi-system inflammatory syndrome MESHD of childhood (MIS-C), at acute(within 72 hours of hospitalization), resolution (at clinical improvement) and convalescent phase. In our cohort, in the acute phase, 68% of the children were SARS-CoV-2 seropositive, with hypercytokinenemia (high interleukin(IL)-1beta HGNC, IL-6 HGNC, IL-8 HGNC, IL-10 HGNC, IL-17 HGNC, interferon gamma HGNC), procoagulant state, myocardial dysfunction MESHD, activated neutrophils and monocytes; differential T and B cell subset lymphopenia MESHD; activated chemokine receptor type-7 positive and gamma-delta T cell subsets; antigen presenting cells had reduced HLA-DR expression; and B-cell class-switch responses occurred with illness resolution. MIS-C is an immunopathogenic illness associated with SARS-CoV-2 infections MESHD in children.

    Risk factors associated with failure of high-flow nasal cannula oxygen therapy in patients with severe COVID-19 MESHD in Wuhan, China

    Authors: Xiao-Huan Ma; Meng-Meng An; Fang Yin; Jie Zhang; Meng-Yun Peng; Hong Guan; Ping Gong

    doi:10.21203/rs.3.rs-41316/v2 Date: 2020-07-12 Source: ResearchSquare

    Background: Acute hypoxemic respiratory failure MESHD is prevalent in severe Coronavirus Disease 2019 MESHD ( COVID-19 MESHD). High-flow nasal canula oxygen therapy (HFNC) is currently one of the most common ventilation strategies for COVID-19 MESHD patients with respiratory failure MESHD. This study is to analyze the risk factors associated with HFNC failure MESHD in patients with severe COVID-19 MESHD.Methods: In this single-center, retrospective, observational study, we enrolled patients with confirmed severe COVID-19 MESHD admitted to Renmin Hospital of Wuhan university (Wuhan, China) from 1 February 2020 to 26 March 26 2020. Epidemiological, clinical, and laboratory data, and treatments and outcomes upon hospital admission, were obtained from electronic medical records. Sequential organ failure assessment (SOFA) scores were calculated.Results: Of 54 patients with severe COVID-19 MESHD, HFNC was successful in 28 (51.9%) and unsuccessful in 26 (48.1%). HFNC failure MESHD was seen more commonly in patients aged ≥60 years and in men. In addition, compared with patients successfully treated with HFNC, patients with HFNC failure MESHD had the following characteristics: higher percentage of fatigue MESHD and anorexia MESHD as well as cardiovascular disease MESHD; increased time from onset to diagnosis and SOFA scores; elevated body temperature, respiratory rate, and heart rate; more complications including ARDS, septic shock MESHD, myocardial damage MESHD, and acute kidney injury MESHD; increased C-reactive protein HGNC, neutrophil counts and prothrombin time; and decreased arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) (all P < 0.05). However, binary logistic regression analysis showed that only male, PaO2/FiO2 and SOFA scores were independent risk factors significantly associated with HFNC failure MESHD (all P < 0.05). Conclusion: Patients with severe COVID-19 MESHD had a high HFNC treatment failure rate. Male, low PaO2/FiO2 and SOFA scores were independent risk factors associated with HFNC failure MESHD in severe COVID-19 MESHD patients. However, studies with larger sample sizes or multi-center studies are warranted. 

    Clinical Features of Hemodialysis (HD) patients confirmed with Coronavirus Disease 2019 MESHD ( COVID-19 MESHD): a Retrospective Case-Control Study

    Authors: Xiaohui Wang; Huan Zhou; Xiaofen Xiao; Xianhua Tan; Xin Zhang; Yong He; Jing Li; Guosheng Yang; Mingmei Li; Duan Liu; Shanshan Han; Haibo Kuang

    doi:10.1101/2020.07.06.20147827 Date: 2020-07-10 Source: medRxiv

    Background: Since December 2019, Coronavirus Disease 2019 MESHD( COVID-19 MESHD) occurred in wuhan, China, and outbreaked rapidly into a global pandemic. This current poses great challenges to hemodialysis (HD) patients. Objective: To make a comprehensive evaluation and comparison between HD patients confirmed with COVID-19 MESHD and the general HD patients. Methods: HD patients confirmed with COVID-19 MESHD in Wuhan No.5 Hospital were admitted as confirmed group from Jan 10 to Mar 15, 2020. And HD patients not infected in our dialysis center were chosen as control group. General characteristics, laboratory indicators were retrospectively collected, analyzed and compared. Results: A total of 142 cases were admitted, including 43 cases in confirmed group and 99 in control group. Body mass index (BMI) was slightly lower in confirmed group than that in control group (P=0.011). The proportion of one or less underlying disease in confirmed group(51.16%) was higher than that in control group(14.14%)(P< 0.001), and the proportion of three or more underlying diseases in confirmed group(11.63%) was lower than that in control group(52.53%)(P< 0.001). Patients in confirmed group exhibited significantly lower hemoglobin, lymphocyte count, and lymphocyte percentage, but higher neutrophil percentage, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein, aspartate transaminase, and alkaline phosphatase HGNC. There was no significant difference in age, gender, dialysis age, primary disease MESHD, the using of ACEI/ARB, platelet-to-lymphocyte ratio (PLR) , and other indicators between the two groups. Conclusions: Faced with Severe Acute Respiratory Syndrome-CoV-2 MESHD (SARS-CoV-2), HD patients with lower BMI and hemoglobin were more susceptible to be infected MESHD, which might be related to malnutrition. Once confirmed with COVID-19 MESHD, HD patients expressed obviously disregulated in inflammation MESHD and immune.

    County-Level Longitudinal Clustering of COVID-19 MESHD Mortality to Incidence Ratio in the United States

    Authors: Nasim Vahabi; Masoud Salehi; Julio Duarte; Abolfazl Mollalo; George Michailidis

    doi:10.21203/rs.3.rs-40632/v2 Date: 2020-07-07 Source: ResearchSquare

    Background: As of November 12, 2020, the mortality to incidence ratio (M IR) HGNC of COVID-19 MESHD was 5.8% in the US. We utilized a longitudinal MESHD model-based clustering system based on the disease trajectories over time. We aimed to find the so-called “vulnerable” cluster of counties where to dedicate additional resources by the US policymakers.  Methods: County-level COVID-19 MESHD cases and deaths (Mar-Nov 2020), and a set of potential risk factors were collected for 3050 U.S. counties during the 1st wave (Mar25-Jun3, 2020), 1344 counties (sunbelt region) during the 2nd wave (Jun4-S ep2, HGNC 2020), and 1055 counties (great plains) during the 3rd wave (S ep3- HGNCNov12, 2020). We used growth mixture models to identify clusters of counties exhibiting similar COVID-19 MESHD M IR HGNCgrowth trajectories and risk-factors over time. Results: We identified the so-called “more vulnerable” clusters during the 1st, 2nd and 3rd waves of COVID-19 MESHD. Tuberculosis MESHD (OR=1.3-2.1-3.2), drug use disorder MESHD (OR=1.1), hepatitis MESHD (OR=13.1), HIV/AIDS MESHD (OR=2.3), cardiomyopathy MESHD and myocarditis MESHD (OR=1.3), diabetes MESHD (OR=1.2), mesothelioma MESHD (OR=9.3) were significantly associated with increased odds of being in a more vulnerable cluster. Heart complications MESHD and cancer MESHD were the main risk factors increasing the COVID-19 MESHD MIR (range: 0.08%-0.52% M IR↑ HGNC).Conclusion: We identified the so-called “more vulnerable” county-clusters exhibiting the highest COVID-19 MESHD MIR trajectories, indicating that enhancing the capacity and access to healthcare resources would be key to successfully manage COVID-19 MESHD in these clusters. These findings provide insights for public health policymakers on the groups of people and locations they need to pay particular attention while managing the COVID-19 MESHD epidemic.

    Risk factors associated with failure of high-flow nasal cannula oxygen therapy in patients with severe COVID-19 MESHD in Wuhan, China

    Authors: Xiao-huan Ma; Fang Yin; Jie Zhang; Meng-yun Peng; Hong Guan; Ping Gong

    doi:10.21203/rs.3.rs-37538/v1 Date: 2020-06-22 Source: ResearchSquare

    Background Acute hypoxemic respiratory failure MESHD is prevalent in severe Coronavirus Disease 2019 MESHD ( COVID-19 MESHD). High-flow nasal canula (HFNC) is currently the most common ventilation strategy for COVID-19 MESHD patients with respiratory failure MESHD. This study is to analyze the risk factors associated with high-flow nasal canula (HFNC) oxygen therapy failure MESHD in patients with severe COVID-19 MESHD.Methods: In this single-center, retrospective, observational study, we enrolled patients with confirmed severe COVID-19 MESHD admitted to Renmin Hospital of Wuhan university (Wuhan, China) from 1 February 2020 to 26 March 26 2020. Epidemiological, clinical, and laboratory data, and treatments and outcomes upon hospital admission, were obtained from electronic medical records. Sequential organ failure assessment (SOFA) scores were calculated.Results: Of 54 patients with severe COVID-19 MESHD, HFNC was successful in 28 (51.9%) and unsuccessful in 26 (48.1%). HFNC failure MESHD was seen more commonly in patients aged ≥60 years and in men. In addition, compared with patients successfully treated with HFNC, patients with HFNC failure MESHD had the following characteristics: higher percentage of fatigue MESHD and anorexia MESHD as well as cardiovascular disease MESHD; increased time from onset to diagnosis and SOFA scores; elevated body temperature, respiratory rate, and heart rate; more complications including ARDS, septic shock MESHD, myocardial damage MESHD, and acute kidney injury MESHD; increased neutrophil counts and prothrombin time; and decreased arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) (all P < 0.05). However, binary logistic regression analysis showed that only male gender and PaO2/FiO2 were independent risk factors significantly associated with HFNC failure MESHD (both, P < 0.05). Conclusion: Patients with severe COVID-19 MESHD had a high HFNC treatment failure rate. Male gender and decreased PaO2/FiO2 were independent risk factors associated with HFNC failure MESHD in severe COVID-19 MESHD patients.

    Cardiovascular Risk Factors and Evolution of Patients Attended with COVID-19 MESHD in a National Reference Hospital from Lima, Peru

    Authors: Germán V. Valenzuela; Alfonso J. Rodriguez-Morales; Roxana Mamani; Ricardo Ayala; Katherine Pérez; Cynthia Sarmiento; Jessica Calcino; Luis García; José Amado

    id:10.20944/preprints202006.0237.v1 Date: 2020-06-19 Source: Preprints.org

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) fatal outcomes have been associated with multiple cardiovascular risk factors. In new epidemic areas, such as Latin America, there is a lack of studies about this. Here, we evaluated those factors in a retrospective cohort of patients in a national reference hospital of Lima, Peru. Design. A retrospective cohort observational study was done. For this study, information was obtained from clinical records of the hospital for the cases that were laboratory-diagnosed and related, during March 6 HGNCth and April 30th, 2020. rRT-PCR was used for the detection of the RNA of SARS-CoV-2 following the protocol Charité, Berlin, Germany, from nasopharyngeal swabs at the National Institute of Health. Calculation of the odds ratio (OR) with the respective 95% confidence interval (95% CI) was done, also logistic regression for adjusted OR (multivariate) was done. Values of p < 0.05 were considered significant for all analyses. Results. One hundred six hospitalized patients were evaluated. The mean age of patients was 61.58 years (SD 16.81). Cardiovascular risk factors among them were hypertension MESHD (46.2%), diabetes MESHD (28.3%), and obesity MESHD (28.3%), among others. Fifty-six patients died (52.8%). Mortality associated factors at the multivariate analysis were arterial hypertension MESHD (OR=1.343, 95% 1.089-1.667), myocardial injury MESHD (OR=1.303, 95% 1.031-1.642), and mechanical ventilation (OR 1.262, 95% 1.034-1.665), as associated factors. Conclusion. As observed in other regions of the world, cardiovascular risk factors represent a significant and independent threat to be considered in patients with COVID-19 MESHD. Further studies and interventions in Peru and Latin America are expected.

    Baseline echocardiographic assessment of left ventricle kinetics alteration and mortality risk in a cohort of critically ill COVID-19 MESHD patients

    Authors: Davide Ceccato; Beatrice Gusella; Mattia Grassi; Alessandro Toffolon; Anna Postal; Davide Gorgi; Federico Capone; Alois Saller; Alberto Cipriani; Cristiano Sarais; Roberto Vettor; Raffaele Pesavento

    doi:10.21203/rs.3.rs-35798/v1 Date: 2020-06-15 Source: ResearchSquare

    Background SARS-CoV2 infection MESHD are frequently associated with cardiovascular manifestations, in particular with symptomatic acute coronary syndromes MESHD, cardiac arrhythmias MESHD and acute heart failure MESHD. However, the elevation of serum troponin seems to be non specific, and a cardiologic diagnostic workup should be performed. We aimed to assess the clinical characteristic and the prevalence of left ventricular (LV) dyssynergy patterns MESHD in a cohort of hospitalized non-critically ill COVID-19 MESHD patientsMethods Consecutive patients with an objective diagnosis of COVID-19 MESHD, from February to April 2020. Baseline characteristics and comorbidities was collected. In case of increased troponin levels or symptoms suggestive for a concomitant cardiac syndrome MESHD, patients undergo to serial electrocardiograms, serial Troponin tests and bedside transthoracic echocardiogram.Results 402 consecutive patients were enrolled: 55 patients underwent an echocardiographic exam because of an increase in troponin levels or a suspected myocardial injury MESHD. Segmental left ventricular abnormalities MESHD were found in 10 (median WMSI 2.03 IQR 1.38-2.75) with a median LV MESHD ejection fraction was 30.1 % IQR, median troponin level was 3083 ng/L, median BNP HGNC was 761 ng/L. Death for any cause occurred in 4 patients among patients with regional LV abnormalities MESHD and in 3 with normal regional function (p= 0,02).Discussion A single bedside transthoracic echocardiogram performed in non critically ill COVID-19 MESHD patients with suspected cardiac injury MESHD has the potential to better assist clinicians in their challenging decision process. As an isolated increase of troponin levels is common in COVID patients, a bed-side echocardiographic evaluation of cardiac function should be routinely implemented during their early evaluation.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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