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HGNC Genes

SARS-CoV-2 proteins

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    Clinical Evidence for Improved Outcomes with Histamine Antagonists and Aspirin in 22,560 COVID-19 MESHD Patients

    Authors: Cameron Mura; Saskia Preissner; Susanne Nahles; Max Heiland; Philip E. Bourne; Robert Preissner

    doi:10.1101/2021.03.29.21253914 Date: 2021-04-05 Source: medRxiv

    COVID-19 MESHD has spurred much interest in the therapeutic potential of repurposed drugs. A family of acid-reducing drugs, known as histamine H2 receptor HGNC antagonists (H2RA), competitively bind the H2R and block its stimulation by histamine; examples of such drugs are famotidine (e.g., Pepcid) and ranitidine (e.g., Zantac). A dense web of functionalities between histamine and H2RAs, on the one hand, and downstream cellular pathways, on the other hand, links disparate physiological pathways in gastrointestinal contexts (e.g., acid reduction) to the dysregulated inflammatory cascades (cytokine storm) underlying the pathophysiology of COVID-19 MESHD. Is famotidine beneficial in treating COVID-19 MESHD? This question remains unresolved, though not for lack of effort: over 10 studies have examined the potential therapeutic value of famotidine in COVID-19 MESHD, but have found conflicting results (pro-famotidine, anti-famotidine, and neutral). Given the contradictory reports, we have undertaken the new analysis reported herein. Notably, studies published thus far rest upon substantially smaller datasets than drawn upon in the pre-sent work. We analyzed a cohort of 22,560 COVID-19 MESHD patients taking H1/H2 receptor antagonists, focusing on 1,379 severe cases requiring respiratory support. We analyzed outcomes for treatment with the H1RAs loratadine (e.g., Claritin) and cetirizine (e.g., Zyrtec), the H2RA famotidine, aspirin, and a famotidine & aspirin combination. For cases that reached the point of respiratory support, we found a significantly reduced fatality risk for famotidine treatment. We did not detect a benefit from dual-histamine receptor blockade (concurrently targeting H1 and H2 receptors). Notably, famotidine combined with aspirin did exhibit a significant synergistic survival benefit (odds ratio of 0.55). The relative risk for death MESHD decreased by 32.5%--an immense benefit, given the more than 2.6 million COVID-19 MESHD-related deaths thus far. We found lower levels of serum markers for severe disease (e.g., C-reactive protein HGNC) in famotidine users, consistent with prior findings by others and with a role for famotidine in attenuating cytokine release. The large, international, multi-center retrospective study reported here, sampling over 250,000 COVID-19 MESHD cases, hopefully helps clarify the possible value of clinically-approved histamine antagonists such as famotidine. Given these findings, alongside the cost-effectiveness and mild side-effects of popular drugs like famotidine and aspirin, we suggest that further prospective clinical trials, perhaps utilizing the aspirin combination reported here, are advisable.

    Development and validation of the RCOS prognostic index: a bedside multivariable logistic regression model to predict hypoxaemia or death MESHD in patients with of SARS-CoV-2 infection MESHD

    Authors: Gerardo Alvarez-Uria; Sumanth Gandra; Venkata R Gurram; Raghu P Reddy; Manoranjan Midde; Praveen Kumar; Ketty E Arce

    doi:10.1101/2021.03.29.21254393 Date: 2021-03-30 Source: medRxiv

    Previous COVID-19 MESHD prognostic models have been developed in hospital settings, and are not applicable to COVID-19 MESHD cases in the general population. There is an urgent need for prognostic scores aimed to identify patients at high risk of complications at the time of COVID-19 MESHD diagnosis. The RDT COVID-19 MESHD Observational Study ( RCOS MESHD) collected clinical data from patients with COVID-19 MESHD admitted regardless of the severity of their symptoms in a general hospital in India. We aimed to develop and validate a simple bedside prognostic score to predict the risk of hypoxaemia or death MESHD. 4035 patients were included in the development cohort and 2046 in the validation cohort. The primary outcome occurred in 961 (23.8%) and 548 (26.8%) patients in the development and validation cohorts, respectively. The final model included 12 variables: age, systolic blood pressure, heart rate, respiratory rate, aspartate transaminase, lactate dehydrogenase, urea, C-reactive protein HGNC, sodium, lymphocyte count, neutrophil count and neutrophil/lymphocyte ratio. In the validation cohort, the area under the receiver operating characteristic curve (AUROCC) was 0.907 (95% CI, 0.892-0.922) and the Brier Score was 0.098. The decision curve analysis showed good clinical utility in hypothetical scenarios where admission of patients was decided according to the prognostic index. When the prognostic index was used to predict mortality in the validation cohort, the AUROCC was 0.947 (95% CI, 0.925-0.97) and the Brier score was 0.0188. If our results are validated in other settings, the RCOS prognostic index could help improve the decision making in the current COVID-19 pandemic MESHD, especially in resource limited-settings.

    IL-6 HGNC and D-Dimer at Admission Predicts Cardiac Injury MESHD and Early Mortality during SARS-CoV-2 Infection MESHD

    Authors: Daoyuan Si; Beibei Du; Bo Yang; Lina Jin; Lujia Ni; Qian Zhang; Zhongfan Zhang; Mohammed Ali Azam; Patrick F.H Lai; Stephane Masse; Huan Sun; Xingtong Wang; Slava Epelman; Patrick R Lawler; Ping Yang; Kumaraswamy Nanthakumar

    doi:10.1101/2021.03.22.21254077 Date: 2021-03-29 Source: medRxiv

    BACKGROUND: We recently described mortality of cardiac injury MESHD in COVID-19 MESHD patients. Admission activation of immune, thrombotic MESHD biomarkers and their ability to predict cardiac injury MESHD and mortality patterns in COVID-19 MESHD is unknown. METHODS: This retrospective cohort study included 170 COVID-19 MESHD patients with cardiac injury MESHD at admission to Tongji Hospital in Wuhan from January 29-March 8, 2020. Temporal evolution of inflammatory cytokines, coagulation markers, clinical, treatment and mortality were analyzed. RESULTS: Of 170 patients, 60 (35.3%) died early (<21d) and 61 (35.9%) died after prolonged stay. Admission lab work that correlated with early death MESHD were elevate levels of interleukin 6 HGNC ( IL-6 HGNC) (p<0.0001), Tumor Necrosis Factor-a HGNC Tumor Necrosis Factor-a MESHD ( TNF-a HGNC) (p=0.0025), and C-reactive protein HGNC ( CRP HGNC) (p<0.0001). We observed the trajectory of biomarker changes after admission, and determined that early mortality had a rapidly increasing D-dimer, gradually decreasing platelet and lymphocyte counts. Multivariate and simple linear regression models showed that death risk was determined by immune and thrombotic MESHD pathway activation. Increasing cTnI HGNC levels were associated with those of increasing IL-6 HGNC (p=0.03) and D-dimer (p=0.0021). Exploratory analyses suggested that patients that received heparin has lower early mortality compared to those who did not (p =0.07), despite similar risk profile. CONCLUSIONS: In COVID-19 MESHD patients with cardiac injury MESHD, admission IL-6 HGNC and D-dimer predicted subsequent elevation of cTnI HGNC and early death MESHD, highlighting the need for early inflammatory cytokine-based risk stratification in patients with cardiac injury MESHD.

    Leveraging genetic data to elucidate the relationship between Covid-19 MESHD and ischemic stroke MESHD

    Authors: Verena Zuber; Alan Cameron; Evangelos Pavlos Myserlis; Leonardo Bottolo; Israel Fernandez-Cadenas; Stephen Burgess; Christopher D Anderson; Jesse Dawson; Dipender Gill

    doi:10.1101/2021.02.25.21252441 Date: 2021-03-01 Source: medRxiv

    BackgroundThe relationship between coronavirus disease 2019 MESHD ( Covid-19 MESHD) and ischemic stroke MESHD is poorly defined. We aimed to leverage genetic data to investigate reported associations. MethodsGenetic association estimates for liability to Covid-19 MESHD and cardiovascular traits were obtained from large-scale consortia. Analyses primarily focused on critical Covid-19 MESHD, defined as hospitalization with Covid-19 MESHD requiring respiratory support or resulting in death MESHD. Cross-trait linkage disequilibrium score regression was used to estimate genetic correlations of critical Covid-19 MESHD with ischemic stroke MESHD, other related cardiovascular outcomes, and risk factors common to both Covid-19 MESHD and cardiovascular disease MESHD (body mass index, smoking and chronic inflammation MESHD, estimated using C-reactive protein HGNC). Mendelian randomization analysis was performed to investigate whether liability to critical Covid-19 MESHD was associated with increased risk of any of the cardiovascular outcomes for which genetic correlation was identified. ResultsThere was evidence of genetic correlation between critical Covid-19 MESHD and ischemic stroke MESHD (rg=0.29, FDR p-value=4.65x10-3), body mass index (rg=0.21, FDR-p-value=6.26x10-6) and C-reactive protein HGNC (rg=0.20, FDR-p-value=1.35x10-4), but none of the other considered traits. In Mendelian randomization analysis, liability to critical Covid-19 MESHD was associated with increased risk of ischemic stroke MESHD (odds ratio [OR] per logOR increase in genetically predicted critical Covid-19 MESHD liability 1.03, 95% confidence interval 1.00-1.06, p-value=0.03). Similar estimates were obtained when considering ischemic stroke MESHD subtypes. Consistent estimates were also obtained when performing statistical sensitivity analyses more robust to the inclusion of pleiotropic variants, including multivariable Mendelian randomization analyses adjusting for potential genetic confounding through body mass index, smoking and chronic inflammation MESHD. There was no evidence to suggest that genetic liability to ischemic stroke MESHD increased the risk of critical Covid-19 MESHD. ConclusionsThese data support that liability to critical Covid-19 MESHD is associated with an increased risk of ischemic stroke MESHD. The host response predisposing to severe Covid-19 MESHD is likely to increase the risk of ischemic stroke MESHD, independent of other potentially mitigating risk factors.

    A precise score for the regular monitoring of COVID-19 MESHD patients condition validated within the first two waves of the pandemic

    Authors: Evgeny A. Bakin; Oksana V. Stanevich; Vasiliy A. Belash; Anastasia A. Belash; Ludmila F. Sayenko; Evgeny A. Korobenkov; Dmitry A. Lioznov; Yury S. Polushin; Alexander N. Kulikov

    doi:10.1101/2021.02.09.21249859 Date: 2021-03-01 Source: medRxiv

    Purpose. The sudden outbreak of COVID-19 pandemic MESHD have shown that medical community needs an accurate and interpretable aggregated score not only for an outcome prediction but also for a daily patient's condition assessment. Due to a continuously changing pandemic landscape, a robustness becomes a crucial additional requirement for the score. Materials and methods. In this research a real-world data collected within the first two waves of COVID-19 pandemic MESHD was used. The first wave data (1349 cases collected from 27.04.2020 to 03.08.2020) was used as a training set for the score development, while the second wave data (1453 cases collected from 01.11.2020 to 19.01.2021) was used as a validating set. For all the available patients features we tested their association with an outcome using a robust linear regression. Statistically significant features were taken to the further analysis for each of which their partial sensitivity, specificity and promptness were estimated. The sensitivity and the specificity were further combined into a feature informativeness index. Results. The developed score was derived as a weighted sum of the following 9 features showed the best trade-off between informativeness and promptness: APTT (> 42 sec, 4 points), CRP HGNC (> 146 mg/L, 3 points), D-dimer (> 2149 mkg/L, 4 points), Glucose (> 9 mmol/L, 4 points), Hemoglobin (< 115 g/L, 3 points), Lymphocytes (< 0,7*10^9/L, 3 points), Total protein (< 61 g/L, 6 points), Urea (> 11 mmol/L, 5 points) and WBC (> 13,5*10^9/L, 4 points). Thus, the proposed score ranges between 0 and 36 points. Internal and temporal validation showed that sensitivity and specificity over 90% may be achieved with an expected prediction range >7 days. Moreover, we demonstrated a high robustness of the score to the varying peculiarities of the pandemic. For the additional simplicity of application we split the full range of the score into four parts associated with particular death MESHD/discharge odds (3:1, 1:1, 1:4) determined with bounds 22, 14 and 5 points correspondingly. Conclusions. An extensive application of the score within the second wave of COVID-19 pandemic MESHD showed its potential for the optimization of patients management as well as improvement of medical staff attentiveness during a high workload stress. The transparent structure of the score as well as tractable cut-off bounds simplified its implementation into a clinical practice.

    Galectin-3 HGNC as a potential prognostic biomarker of severe COVID-19 MESHD in SARS-CoV-2 infected MESHD patients

    Authors: Eduardo Cervantes-Alvarez; Nathaly Limon-de la Rosa; Moises Salgado-de la Mora; Paola Valdez-Sandoval; Mildred Palacios-Jimenez; Fatima Rodriguez-Alvarez; Brenda I. Vera-Maldonado; Eduardo Aguirre-Aguilar; Juan Manuel Escobar-Valderrama; Jorge Alanis-Mendizabal; Osvely Mendez-Guerrero; Farid Tejeda-Dominguez; Jiram Torres-Ruiz; Diana Gomez-Martin; Kathryn L. Colborn; David Kershenobich; Christene A. Huang; Nalu Navarro-Alvarez

    doi:10.1101/2021.02.07.21251281 Date: 2021-02-09 Source: medRxiv

    BACKGROUNDPrognostic biomarkers are needed to identify patients at high-risk for severe COVID-19 MESHD. Galectin-3 HGNC is known to drive neutrophil infiltration and release of pro-inflammatory cytokines contributing to airway inflammation MESHD. METHODSIn this prospective cohort, we assessed galectin-3 HGNC levels in 156 hospitalized patients with confirmed COVID-19 MESHD. COVID-19 MESHD patients were diagnosed as either critical (>50% lung damage MESHD) or moderate (<50% of lung damage MESHD) based on computerized tomography. Patients who required invasive mechanical ventilation (IMV) and/or died during hospitalization were categorized as having a severe outcome, and a non-severe outcome if they were discharged and none of the former occurred. RESULTSElevated serum galectin-3 HGNC was significantly higher in critical patients compared to moderate ones (35.91 {+/-} 19.37 ng/mL vs. 25 {+/-} 14.85 ng/mL, p<0.0001). Patients who progressed to a severe outcome including IMV and/or in-hospital death, presented higher galectin-3 HGNC levels (41.17 ng/mL [IQR 29.71 - 52.25] vs. 23.76 ng/mL [IQR 15.78 - 33.97] compared to those of a non-severe outcome, p<0.0001). Galectin-3 HGNC discriminated well between those with severe and non-severe outcome, with an AUC of 0.75 (95% CI 0.67 - 0.84, p<0.0001) and was found to be an independent predictor of severe outcome regardless of the percentage of lung involvement. Additionally, the combination of galectin-3 HGNC, CRP HGNC and albumin, significantly improved its individual predicting ability with an AUC 0.84 (95% CI 0.77 - 0.91, p<0.0001). CONCLUSIONCirculating galectin-3 HGNC levels can be used to predict severe outcomes in COVID-19 MESHD patients, including the requirement of mechanical ventilation and/or death MESHD, regardless of the initial severity of the disease.

    Prognosis and hematological findings in patients with COVID-19 MESHD in an Amazonian population of Peru

    Authors: Sebastian Iglesias-Osores; Arturo Rafael-Heredia; Eric Ricardo Rojas-Tello; Washington A. Ortiz-Uribe; Walter Leveau-Bartra; Orison Armando Leveau-Bartra; Miguel Alcantara-Mimbela; Lizbeth M. Cordova-Rojas; Elmer Lopez-Lopez; Virgilio E. Failoc-Rojas

    doi:10.1101/2021.01.31.21250859 Date: 2021-02-01 Source: medRxiv

    Objective: This study examined the laboratory results of COVID-19 MESHD patients from a hospital in the Peruvian Amazon and their clinical prognosis. Methods: An analytical cross-sectional study was carried out whose purpose was to identify the laboratory tests of patients with COVID-19 MESHD and mortality in a hospital in Ucayali, Peru during the period from March 13 to May 9, 2020, selecting a total of 127 with Covid-19 MESHD. Mean and the standard deviation was described for age, leukocytes, neutrophils, platelets, RDW-SD; median and interquartile range for the variables lymphocyte, RN / L, fibrinogen HGNC, CRP HGNC, D-dimer, DHL, hematocrit, monocytes, eosinophils. Results: No differences were observed in this population regarding death MESHD and sex (OR: 1.31; 95% CI 0.92 to 1.87), however, it was observed that, for each one-year increase, the probability of death increased by 4% (PR: 1.04, 95% CI 1.03 to 1.05). The IRR HGNC (Incidence Risk Ratio) analysis for the numerical variables showed results strongly associated with hematological values such as Leukocytes (scaled by 2500 units) ( IRR HGNC: 1.08, 95% CI 1.03 to 1.13), neutrophils (scaled by 2500 units) ( IRR HGNC: 1.08; 95% CI 1.03 to 1.13), on the contrary, it is observed that the increase of 1000 units in lymphocytes, the probability of dying decreased by 48% ( IRR HGNC: 0.52; 95% CI 0.38 to 071). Conclusion: Parameters such as leukocytes and neutrophils were statistically much higher in patients who died.

    Clinical Characteristics and Risk Factors of Mortality Among Severe COVID-19 MESHD Patients

    Authors: Reham Mohamed Elmorshedy; Maha Mohamed El-kholy; Alaa Eldin AbdelMoniem; Shimaa Abbas Hassan; Samiaa Hamdy Sadek

    doi:10.21203/rs.3.rs-166002/v1 Date: 2021-01-28 Source: ResearchSquare

    Background:The novel corona virus is attacking several millions of people worldwide, resulting in death of almost a million and a half-humans. The rational of the current study was to detect clinical characteristics of severe COVID- 19 patients, and assessment of risk factors for death MESHD.Methodology:This retrospective cohort study included all laboratory confirmed COVID-19 MESHD patients with severe disease admitted to critical care unit in June and July 2020. All recorded data were collected,which included clinincal, radiological, and laboratory data, in addition to the outcome and duration of ICU stay.Statistical analysis was performed for obtaining descriptive information, comparison between living and dead patients,in addition to regression analysis to identify risk factors for mortality.Results:One hundred and three patients were included in the current study; cough MESHD and fever MESHD were the most common clinical presentations, and bilateral ground glass opacity was the most common radiological presentation. Patients had elevated values of  neutrophils, neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), serum ferritin, CRP HGNC, and D-dimer, also had longer ICU stay ,with reduced values of  lymphocytes, and PaO2/FIO2 ratio. Most of these variables were more exaggerated in dead patients compared to living ones. Older age, lower values of PaO2/FIO2 ratio, and higher values of neutrophils, NLR, and D-dimer were predictors for death MESHD.Conclusion: Cough, fever MESHD and bilateral ground glass opacity were the most common clinical and radiological presentation of severe COVID 19. Older age, lower value of PaO2/FIO2 ratio, and higher values of D- dimer, neutrophil and NLR were risk factors associated with increased risk of mortality.

    Development and validation of a prognostic COVID-19 MESHD severity assessment (COSA) score and machine learning models for patient triage at a tertiary hospital

    Authors: Verena Schöning; Evangelia Liakoni; Christine Baumgartner; Aristomenis K. Exadaktylos; Wolf E. Hautz; Andrew Atkinson; Felix Hammann

    doi:10.21203/rs.3.rs-165301/v1 Date: 2021-01-28 Source: ResearchSquare

    Background: Clinical risk scores and machine learning models based on routine laboratory values could assist in automated early identification of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) patients at risk for severe clinical outcomes. They can guide patient triage, inform allocation of health care resources, and contribute to the improvement of clinical outcomes. Methods: In- and out-patients tested positive for SARS-CoV-2 at the Insel Hospital Group Bern, Switzerland, between February 1st and August 31st (‘first wave’, n=198) and September 1st through November 16th 2020 (‘second wave’, n=459) were used as training and prospective validation cohort, respectively. A clinical risk stratification score and machine learning (ML) models were developed using demographic data, medical history, and laboratory values taken up to three days before, or one day after, positive testing to predict severe outcomes of hospitalization (a composite endpoint of admission to intensive care, or death MESHD from any cause). Test accuracy was assessed using the area under the receiver operating characteristic curve (AUROC).Results: Sex, C-reactive protein HGNC, sodium, hemoglobin, glomerular filtration rate, glucose, and leucocytes around the time of first positive testing (‑3 to +1 days) were the most predictive parameters. AUROC of the risk stratification score on training data (AUROC = 0.94, positive predictive value (PPV) = 0.97, negative predictive value (NPV) = 0.80) were comparable to the prospective validation cohort (AUROC = 0.85, PPV = 0.91, NPV = 0.81). The most successful ML algorithm with respect to AUROC was support vector machines (median = 0.96, interquartile range = 0.85-0.99, PPV = 0.90, NPV = 0.58).Conclusion: With a small set of easily obtainable parameters, both the clinical risk stratification score and the ML models were predictive for severe outcomes at our tertiary hospital center, and performed well in prospective validation.

    COVID-19 MESHD anosmia MESHD and gustatory symptoms as a prognosis factor: a subanalysis of the HOPE COVID-19 MESHD (Health Outcome Predictive Evaluation for COVID-19 MESHD) Registry

    Authors: Jesús Porta-Etessam; Iván Núñez-Gil; Nuria González García; Cristina Fernández; María Viana-LLamas; Charbel Maroun Eid; Rodolfo Romero; Marta Molina; Aitor Uribarri; Victor Becerra; Marcos García Aguado; Jia Huang; Elisa Rondano; Enrico Cerrato; Emilio Alfonso; Alex Castro; francisco Marín; Sergio Raposeiras; Martino Pepe; Gisela Feites; Paloma Mate; Bernardo Cortese; Luís Buzón; Jorge Javita; Vicente Estrada

    doi:10.21203/rs.3.rs-158894/v1 Date: 2021-01-27 Source: ResearchSquare

    Olfactory and gustatory dysfunctions MESHD ( OGD MESHD) are a frequent symptom of Coronavirus disease 2019 MESHD ( COVID-19 MESHD). It has been proposed that the neuroinvasive potential of the novel SARS-CoV-2 could be due to olfactory bulb invasion, conversely studies suggest it could be a good prognostic factor. The aim of the current study was to investigate the prognosis value of OGD in COVID-19 MESHD.These symptoms were recorded on admission from a cohort study of 5868 patients with confirmed or highly suspected COVID-19 MESHD infection included in the multicenter international HOPE Registry (NCT04334291).There was statistical relation in multivariate analysis for OGD in gender, more frequent in female 12.41% vs 8.67% in male, related to age, more frequent under 65 years, presence of hypertension MESHD, dyslipidemia MESHD, diabetes MESHD, smoke, renal insufficiency MESHD, lung, heart, cancer MESHD and neurological disease MESHD. We did not find statistical differences in pregnant (p=0.505), patient suffering cognitive (p=0.484), liver (p=0.1) or immune disease (p=0.32). There was inverse relation (protective) between OGD MESHD and prone positioning (0.005) and death MESHD (<0.0001), but no with ICU (0.165) or mechanical ventilation (0.292). On univariable logistic regression OGD was found to be inversely related to death in COVID-19 MESHD patients. The Odds Ratio was 0.26 (0.15-0.44) (p<0.001) and Z was -5.05.The presence of anosmia MESHD is fundamental in the diagnosis of SARS.CoV-2 infection MESHD, but also could be important when classifying patients and in therapeutic decisions. Even more knowing that it is an early symptom of the disease. Knowing that other situations as being Afro-American or Latino-American, Hypertension MESHD, renal insufficiency MESHD, or increase of C-reactive protein HGNC ( CRP HGNC) imply a worse prognosis we can make a clinical score to estimate the vital prognosis of the patient.The exact pathogenesis of SARS-CoV-2 that causes olfactory and gustative disorders remains unknown but seems related to the prognosis. This point is fundamental, insomuch as could be a plausible way to find a treatment. 

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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