Corpus overview


MeSH Disease

Human Phenotype


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    Understanding Structural Malleability of the SARS-CoV-2 Proteins MESHD and their Relation to the Comorbidities

    Authors: Sagnik Sen; Ashmita Dey; Sanghamitra Bandyopadhyay; Ujjwal Maulik; Vladimir Uversky

    doi:10.21203/ Date: 2020-09-23 Source: ResearchSquare

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), a causative agent of the coronavirus disease MESHD (CoVID-19), is a part of the β-coronaviridae family. In comparison with two other members of this family TRANS of coronaviruses infecting humans ( SARS-CoV and Middle East Respiratory Syndrome MESHD ( MERS MESHD) CoV), SARS-CoV-2 showed the most severe effects on the entire Earth population causing world-wide CoVID-19 pandemic. SARS-CoV-2 contains five major protein classes, such as four structural proteins (Nucleocapsid (N), Membrane (M), Envelop (E), and Spike Glycoprotein (S)) and Replicase polyproteins (R), which are synthesized as two polyproteins (ORF1a and ORF1ab) that are subsequently processed into 12 nonstructural proteins by three viral proteases. All these proteins share high sequence similarity with their SARS-CoV MESHD counterparts. Due to the severity of the current situation, most of the SARS-CoV-2-related research is focused on finding therapeutic solutions and the analysis of comorbidities during infection MESHD. However, studies on the peculiarities of the amino acid sequences of viral protein classes and their structure space analysis throughout the evolutionary time-frame are limited. At the same time, due to their structural malleability, viral proteins can be directly or indirectly associated with the dysfunctionality of the host cell proteins, which may lead to comorbidities during the infection and at the post infection stage. To fill these gaps, we conducted the evolutionary sequence-structure analysis of the viral protein classes to evaluate the rate of their evolutionary malleability. We also looked at the intrinsic disorder propensities of these viral proteins and confirmed that although they typically do not have long intrinsically disordered regions (IDRs), all of them have at least some levels of intrinsic disorder MESHD. Furthermore, short IDRs found in viral proteins are extremely effective and prioritize the proteins for host cell interactions, which may lead to host cell dysfunction. Next, the associations of viral proteins with the host cell proteins were studied, and a list of diseases which are associated with such host cell proteins was developed. Other than the usual set of diseases, we have identified some maladies, which may happen after the recovery from the infections. Comparison of the expression rates of the host cell proteins during the diseases suggested the existence of two distinct classes. First class includes proteins, which are directly associated with certain sets of diseases, where they have shared similar activities. Second class is related to the cytokine storm-mediated pro- inflammation MESHD (already known for its role in acute respiratory distress HP respiratory distress MESHD syndrome, ARDS MESHD), and neuroinflammation may trigger some of the neurological malignancies and neurodegenerative and neuropsychiatric diseases MESHD. Finally, since the transmembrane serine protease 2 (TMPRSS2), which is one of the leading proteins associated with the viral uptake, is an androgen-mediated protein, our study suggested that males TRANS and postmenopausal females TRANS can be more susceptible to the SARS-CoV-2 infection MESHD.

    Vent-Lock: A 3D Printed Ventilator Multiplexer to Enhance the Capacity of Treating Patients with COVID-19

    Authors: Helen Xun; Christopher Shallal; Justin Unger; Runhan Tao; Alberto Torres; Michael Vladimirov; Jenna Frye; Mohit Singhala; Brockett Horne; Pooja Yesantharao; Bo Soo Kim; Broc Burke; Michael Montana; Michael Talcott; Bradford Winters; Margaret Frisella; Bradley Kushner; Justin Sacks; James Guest; Sung Hoon Kang; Julie Caffrey

    doi:10.1101/2020.09.16.20195230 Date: 2020-09-22 Source: medRxiv

    Mechanical ventilators are essential to patients who become critically ill from acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD), and shortages have been reported due to the novel severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2). We utilized cost-effective, on-demand 3D printing (3DP) technology to produce critical components for a novel ventilator multiplexer system, Vent-Lock, to split one ventilator or anesthesia gas machine between two patients. FloRest, a novel 3DP flow restrictor, provides clinicians control of tidal volumes and positive end expiratory pressure (PEEP), using the 3DP manometer adaptor to monitor pressures. We tested the ventilator splitter circuit in simulation centers between artificial lungs and used an anesthesia gas machine to successfully ventilate two swines. As one of the first studies to demonstrate splitting one anesthesia gas machine between two swines, we present proof-of-concept of a de novo, closed, multiplexing system, with flow restriction for individualized patient therapy. Our studies underscore that while possible, ventilator multiplexing is a complicated synergy between machine settings, circuit modification, and patient monitoring. Consequently, ventilator multiplexing is reserved only as a last emergency resource, by trained clinicians and respiratory therapists with ventilator operative experience.

    Proteomics identifies a type I IFN, prothrombotic hyperinflammatory circulating COVID-19 neutrophil signature distinct from non-COVID-19 ARDS

    Authors: Leila Reyes; Manuel Alejandro Sanchez-Garcia; Tyler Morrison; Andrew JM Howden; Emily R Watts; Simone Arienti; Pranvera Sadiku; Patricia Coelho; Ananda S Mirchandani; David Hope; Sarah K Clark; Jo Singleton; Shonna Johnston; Robert Grecian; Azin Poon; Sarah McNamara; Isla Harper; Max Head Fourman; Alejandro J Brenes; Shalini Pathak; Amy Lloyd; Gio Rodriguez Blanco; Alex Von Kriegsheim; Bart Ghesquiere; Wesley Vermaelen; Camila T Cologna; Kevin Dhaliwal; Nik Hirani; David Dockrell; Moira KB Whyte; David M Griffith; Doreen A Cantrell; Sarah R Walmsley; Marc P. Hoeppner; Simon Imm; Ralf Juenker; Sina Kaiser; Ying H. Kan; Rainer Knoll; Christoph Lange; Georg Laue; Clemes Lier; Matthias Lindner; Georgios Marinos; Robert Markewitz; Jacob Nattermann; Rainer Noth; Peter Pickkers; Klaus F. Rabe; Alina Renz; Christoph Roecken; Jan Rupp; Annika Schaffarzyk; Alexander Scheffold; Jonas Schulte-Schrepping; Domagoj Schunck; Dirk Skowasch; Thomas Ulas; Klaus-Peter Wandinger; Michael Wittig; Johannes Zimmermann; Hauke Busch; Bimba F. Hoyer; Christoph Kaleta; Jan Heyckendorf; Matthijs Kox; Jan Rybniker; Stefan Schreiber; Joachim Schultze; Philip Rosenstiel; - HCA Lung Biological Network; - Deutsche COVID-19 Omics Initiative (DeCOI)

    doi:10.1101/2020.09.15.20195305 Date: 2020-09-18 Source: medRxiv

    Understanding the mechanisms by which infection with SARS-CoV-2 leads to acute respiratory distress HP respiratory distress MESHD syndrome ( ARDS MESHD) is of significant clinical interest given the mortality associated with severe and critical coronavirus induced disease MESHD 2019 (COVID-19). Neutrophils play a key role in the lung injury MESHD characteristic of non-COVID-19 ARDS, but a relative paucity of these cells is observed at post-mortem in lung tissue of patients who succumb to infection MESHD with SARS-CoV-2. With emerging evidence of a dysregulated innate immune response in COVID-19, we undertook a functional proteomic survey of circulating neutrophil populations, comparing patients with COVID-19 ARDS, non-COVID-19 ARDS, moderate COVID-19, and healthy controls. We observe that expansion of the circulating neutrophil compartment and the presence of activated low and normal density mature and immature neutrophil populations occurs in both COVID-19 and non-COVID-19 ARDS. In contrast, release of neutrophil granule proteins, neutrophil activation of the clotting cascade and formation of neutrophil platelet aggregates is significantly increased in COVID-19 ARDS. Importantly, activation of components of the neutrophil type I IFN responses is specific to infection with SARS-CoV-2 and linked to metabolic rewiring. Together this work highlights how differential activation of circulating neutrophil populations may contribute to the pathogenesis of ARDS, identifying processes that are specific to COVID-19 ARDS.

    Detection of SARS-CoV-2 in peritoneal fluid from patients with kidney disease MESHD and COVID-19: report of two cases

    Authors: Margarita Ibarra-Hernandez; María de la Luz Alcantar-Vallín; Rodolfo I. Cabrera-Silva; Karina Sánchez-Reyes; Monserrat Alvarez-Zavala; Judith C. De Arcos-Jiménez; Luz A. González-Hernández; Vida V. Ruiz-Herrera; Sara A. Aguirre-Díaz; Roxana García-Salcido; Guillermo García-García; Jaime F. Andrade-Villanueva

    doi:10.21203/ Date: 2020-09-16 Source: ResearchSquare

    Background: Coronavirus disease-2019 (COVID-19) has a broad clinical presentation, involving multiple organs besides the respiratory system. Currently, there is little evidence available on the presence of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) in peritoneal fluid (PF). In this study, we describe the detection of SARS-CoV-2 in the PF of two patients with COVID 19 and kidney disease MESHD.Case presentation: Case 1: A 71-year-old woman with a history of end-stage kidney disease MESHD who presented with a 15-day evolution of progressive dyspnea HP dyspnea MESHD, accompanied by dry cough MESHD cough HP and fever HP fever MESHD; IgM antibodies SERO to SARS-CoV-2 were detected on admission. Real-time SARS-CoV-2 polymerase chain reaction (qRT-PCR) in the PF was positive. Three days after admission the patient's respiratory distress HP improved and she was discharged after 8 days of hospitalization.Case 2: A 78-year-old woman, with type 2 diabetes MESHD, hypertension HP hypertension MESHD, a 15-day history of polypnea, and a 5-day onset of fever HP fever MESHD and dyspnea HP dyspnea MESHD. IgM and IgG antibodies SERO to SARS-CoV-2 were detected on admission, as well as a positive nasopharyngeal qRT-PCR test for SARS-CoV-2. During hospitalization she developed acute kidney injury HP acute kidney injury MESHD, requiring peritoneal dialysis, SARS-CoV-2 was confirmed in PF by qRT-PCRConclusions: These two cases highlights the importance of increasing the level of awareness for the presence and possible SARS-CoV-2 transmission TRANS through non-respiratory routes, like peritoneal fluid.Emphasis should be given to appropriate preventive strategies for minimizing the risk of transmission TRANS of COVID-19 from patients on peritoneal dialysis in both inpatient and outpatient settings.

    Respiratory Rehabilitation After Blood SERO Transfusion in a COVID-19 Patient: A Case Report

    Authors: Mohammad Javad Mousavi; Narges Obeidi; Saeed keshmiri; Farzan Azodi; Jamile Kiyani; Farhad Abbasi

    doi:10.21203/ Date: 2020-09-15 Source: ResearchSquare

    Background: The coronavirus disease MESHD 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), has been identified as the most crucial threat of the century. Due to severe pneumonia HP pneumonia MESHD and acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD), the SARS-CoV-2 can cause shortness of breath MESHD, hypoxemia HP hypoxemia MESHD, and the need to mechanical ventilation, intensive care unit (ICU) management, and eventual death MESHD. We have tried to use a non-invasive approach to prevent patient from needing respiratory support with invasive ventilation (IV). Here, for the first time, improvement of oxygen delivery and oxygen saturation levels were observed in a COVID-19 patient using packed red blood SERO cells (PRBCs) transfusion.Case presentation: A 63-year-old man with a history of smoking and addiction who came to our hospital facility with fever HP fever MESHD, shortness of breath MESHD and decreased blood SERO oxygen saturation. High-resolution chest CT revealed bilateral and multifocal ground-glass opacities consistent with COVID-19. Subsequently, the COVID-19 infection was confirmed TRANS infection was confirmed MESHD by real-time polymerase chain reaction (qRT-PCR) assay of the upper respiratory tract. Conclusions: Oxygen delivery and oxygen saturation improvement were observed in the COVID-19 patient, after PRBCs transfusions.

    Decrease of exercise endurance in critically ill COVID-19 survivors: 4 case reports

    Authors: Qian Geng; Xinxin Yu; Beilan Shen; Shiyue Li; Jinping Zheng; Liping Zhong; Yi Hong; Xiaoyan Huang; Qingsi Zeng; Shaoqiang Li; Feng Ye; Weijie Guan; Yanqing Xie; Nanshan Zhong; Yi Gao

    doi:10.21203/ Date: 2020-09-04 Source: ResearchSquare

    Background: The Coronavirus Disease MESHD 2019 (COVID-19) already have been as a pandemic. However, knowledge about the sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD remains limited. Here we descirbe the pulmonary function test (PFT) and cardiopulmonary exercise test (CPET) of critically ill COVID-19 in four cases with sereve acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD) after discharge.Case presentation: We introduce four patients who complained of fever HP fever MESHD, cough HP cough MESHD, chest tightness HP chest tightness MESHD and other symptoms, all of them were confirmed as SARS-CoV-2 infection MESHD by real-time reverse transcription polymerase chain reaction (RT-PCR). They were treated with mechanical ventilation because of severe ARDS MESHD. After respiratory support, antiviral and anti-infective treatment, they were weaned from mechanic ventilation with the improvement of hypoxemia HP hypoxemia MESHD. All patients were discharged from the hospital after completion of treatment and had no mortality. Around 1-month post-discharge, they were followed up for chest computed tomography (CT) scan, and performed PFT and CPET. Peak oxygen uptake of predicted (peakVO2% pred) decreased in all four cases, although spirometry were in the normal range, and only 2 cases had mild decline in carbon monoxide diffusion capacity of predicted (DLCO%pred).Conclusions: We found reduced exercise endurance in all four COVID-19 survivors, even parts of them with normal or slightly abnormal static lung function. We also believe that exercise endurance impairment of COVID-19 convalescents is more likely affected by extrapulmonary factors. Taken the above into consideration, our study highlights that the combination of PFT and CPET are important tests for tracking the development and recovery of COVID-19 survivors.


    Authors: Manju Mamtani; Ambarish M Athavale; Mohan Abraham; Jane Vernik; Amatur Amarah; Juan Ruiz; Amit Joshi; Matthew Itteera; Sara Zhukovsky; Ravi Prakash Madaiah; Peter Hart; Hemant Kulkarni

    doi:10.1101/2020.08.31.20185157 Date: 2020-09-02 Source: medRxiv

    Objective: Diabetes MESHD is a known risk factor for mortality in Coronavirus disease MESHD 2019 (COVID-19) patients. Our objective was to identify prevalence SERO of hyperglycemia HP hyperglycemia MESHD in COVID-19 patients with and without diabetes MESHD and quantify its association with COVID-19 disease course. Research Design and Methods: In this observational cohort study, all consecutive COVID-19 patients admitted to John H Stroger Jr. Hospital, Chicago, IL from March 15, 2020 to May 15, 2020 were included. The primary outcome was hospital mortality and the main predictor was hyperglycemia HP hyperglycemia MESHD (any blood SERO glucose [≥]7.78 mmol/L during hospitalization). Results: Of 403 COVID-19 patients studied, 228 (57%) developed hyperglycemia HP hyperglycemia MESHD. Of these, 83 (21%) had hyperglycemia HP hyperglycemia MESHD without diabetes MESHD. A total of 51 (12.7%) patients died. Compared to the reference group no- diabetes MESHD/no- hyperglycemia HP hyperglycemia MESHD patients the no- diabetes MESHD/ hyperglycemia HP hyperglycemia MESHD patients showed higher mortality (1.8% versus 20.5%, adjusted odds ratio 21.94 (95% confidence interval 4.04-119.0), p < 0.001); improved prediction of death (p=0.0162) and faster progression to death (p=0.0051). Hyperglycemia HP Hyperglycemia MESHD within the first 24 and 48 hours was also significantly associated with mortality (odds ratio 2.15 and 3.31, respectively). Further, compared to the same reference group, no- diabetes MESHD/ hyperglycemia HP hyperglycemia MESHD patients had higher risk of ICU admission (p<0.001), mechanical ventilation (p<0.001) and acute respiratory distress syndrome MESHD respiratory distress HP syndrome (p<0.001) and a longer hospital stay in survivors (p<0.001). Conclusions: Hyperglycemia HP Hyperglycemia MESHD in the absence of diabetes MESHD was common (21% of hospitalized COVID-19 patients) and was associated with an increased risk of and faster progression to death. Development of hyperglycemia HP hyperglycemia MESHD in COVID-19 patients who do not have diabetes MESHD is an early indicator of poor prognosis.

    Pulmonary Hemodynamics and Ventilation in Patients With COVID-19-related Respiratory Failure HP Respiratory Failure MESHD and ARDS

    Authors: André Becker; Frederik Seiler; Ralf M. Muellenbach; Guy Danziger; Sebastian Mang; Albert Omlor; Christophe Jentgen; Maren Kamphorst; Holger Wehrfritz; Christopher Lotz; Thilo Mertke; Heinrike Wilkens; Robert Bals; Philipp M. Lepper

    doi:10.21203/ Date: 2020-08-27 Source: ResearchSquare

    Background: It has been suggested that COVID-19-associated severe respiratory failure HP respiratory failure MESHD (CARDS) might differ from usual acute respiratory distress HP respiratory distress MESHD syndrome ( ARDS MESHD) due to failing auto-regulation of pulmonary vessels and higher shunt. We sought to investigate pulmonary hemodynamics and ventilation properties in patients with CARDS compared to patients with ARDS MESHD of pulmonary origin. Methods: Retrospective analysis of prospectively collected data of consecutive adults TRANS with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 MESHD patients treated on our ICU in 04/2020 and comparison of the data to matched controls with ARDS MESHD due to respiratory infections MESHD treated on our ICU from 01/2014 to 08/2019 and for whom pulmonary artery catheter data were available. Results: CARDS patients (n = 10) had similar ventilation characteristics as compared to ARDS (n = 10) patients. Still, mechanical power applied by ventilation was significantly higher in CARDS patients (23.4 ± 8.9 J/min) than in ARDS (15.9 ± 4.3 J/min; p<0.05). COVID-19 patients had similar pulmonary artery pressure MESHD but significantly lower pulmonary vascular resistance, as cardiac output was higher in CARDS vs. ARDS MESHD patients (p<0.05). Shunt fraction and dead space were similar in CARDS compared to ARDS (p>0.05) and was in both groups correlated with hypoxemia HP hypoxemia MESHD. The arterio-venous pCO2 difference (DpCO2) was elevated (CARDS 5.5±2.8 mmHg vs. ARDS 4.7±1.1 mmHg; p>0.05) as was P(v-a)CO2/C(a-v)O2 ratio (CARDS mean 2.2±1.5 vs. ARDS MESHD 1.7±0.8; p>0.05). Conclusions: Respiratory failure HP Respiratory failure MESHD in COVID-19 patients seems to differ only slightly from ARDS regarding ventilation characteristics and pulmonary hemodynamics. Differences are mainly due to increased CO2 production in CARDS patients. Our data indicate microcirculatory dysfunction. More data needs to be collected to assure these findings and gain more pathophysiological insights in COVID-19 and respiratory failure HP respiratory failure MESHD.

    Diagnosis Challenges, Management, and Outcome of Infants Born to Mothers With COVID 19

    Authors: Gabriela Zaharie; Monica Hasmasanu; Daniel Muresan; Tunde Kovacs; Melinda Matyas

    doi:10.21203/ Date: 2020-08-25 Source: ResearchSquare

    Background: Severe acute respiratory distress HP respiratory distress MESHD syndrome with Coronavirus 2 (SARS-CoV-2) infection MESHD affected the pregnant women during the pandemics. Immunological particularity of this population and the increased need for medical assistance put this population in a high-risk category for SARS-Cov-2 infection MESHD.Because of high contamination risk and limited studies about vertical transmission TRANS, the labor and delivery of positive women require special conditions. Cesarean section is probably the best option for delivery of infants to reduce the risk of infection TRANS risk of infection TRANS infection MESHD during birth.Aim: Our study aims to present the management and outcome of infants born to mothers confirmed with coronavirus disease MESHD 2019 (COVID19) before delivery.Material and methods: This is longitudinal, retrospective study, analyzing demographics, laboratory data and management of neonates born of mothers with diagnosis of SARS-Cov -2 infection MESHD.Results: 5 neonates were born of SARS-Cov-2 positive mothers , all by C- section and had negative real time –PCR ( RT-PCR) test. None of them was breastfed during hospital stay. The negative RT-PCR test allowed us to reduce the hospital stay of infants and care them in non –isolated area.Conclusion: In our study, vertical or perinatal transmission TRANS of the infection was not present. The testing of the pregnant women, their isolation and delivery in safe conditions for the medical staff were possible, using adequate protection equipment to limit their infection and the risk TRANS infection and the risk TRANS infection and the risk MESHD for the newborns.

    Resilience in Cancer Care at the Time of COVID-19: Practical Approach to the Management of Cancer MESHD Patients During the COVID-19 Emergency in a Large Italian Community Hospital

    Authors: Angioletta Lasagna; Simona Secondino; Francesco Agustoni; Teresa Monaco; Ilaria Imarisio; Anna Pagani; Gianpiero Rizzo; Richard J. Tancredi; Emma Pozzi; Elisa Ferraris; Silvia Chiellino; Chiara Gandini; Silvia G. Brugnatelli; Paolo Pedrazzoli

    doi:10.21203/ Date: 2020-08-22 Source: ResearchSquare

    PurposeWith the emergence of coronavirus disease MESHD 2019 (COVID-19), the Oncologists have had to face the challenge of continuing active treatments without compromising the safety of our patients and healthcare personnel. Methods From February 24th, we reorganized our Oncology Unit with the introduction of a double-step triage strategy for cancer MESHD patients under treatment in order to identify patients at risk from COVID-19 and to avoid their admission to the outpatient clinic and to the inpatient ward.ResultsFrom February 24 to April 7 2020, we have performed 819 phone calls, leading to the authorization of 788 accesses (312 patients) to the outpatient clinic for active treatments. 26 patients (8.3%) with symptoms were kept at home and managed by repeated telephone calls; 23 of them were managed at home with symptomatic treatments and antibiotics and the others 3 were hospitalized for suspected COVID. At the second triage level, 5 patients weren’t admitted to the Outpatient clinic for persistent fever HP fever MESHD or respiratory distress HP respiratory distress MESHD.177 patients were admitted to the inpatient ward: none has been found to be COVID-19 positive and both outpatient and inpatient areas were still COVID-19 free. No healthcare workers became infected by SARS-CoV-2.ConclusionOur practical approach based on a simple double-step triage strategy, allows the identification of patients at risk for active COVID-19 infection MESHD, did not request neither human nor economic extra resources and appears effective, within a large community Hospital, in maintaining cancer MESHD care and therapy while protecting patients and healthcare workers from COVID-19 infection MESHD.

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MeSH Disease
Human Phenotype

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