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1.
Sci Rep ; 11(1): 10678, 2021 05 21.
Article in English | MEDLINE | ID: covidwho-1238016

ABSTRACT

With an urgent need for bedside imaging of coronavirus disease 2019 (COVID-19), this study's main goal was to assess inter- and intraobserver agreement in lung ultrasound (LUS) of COVID-19 patients. In this single-center study we prospectively acquired and evaluated 100 recorded ten-second cine-loops in confirmed COVID-19 intensive care unit (ICU) patients. All loops were rated by ten observers with different subspeciality backgrounds for four times by each observer (400 loops overall) in a random sequence using a web-based rating tool. We analyzed inter- and intraobserver variability for specific pathologies and a semiquantitative LUS score. Interobserver agreement for both, identification of specific pathologies and assignment of LUS scores was fair to moderate (e.g., LUS score 1 Fleiss' κ = 0.27; subpleural consolidations Fleiss' κ = 0.59). Intraobserver agreement was mostly moderate to substantial with generally higher agreement for more distinct findings (e.g., lowest LUS score 0 vs. highest LUS score 3 (median Fleiss' κ = 0.71 vs. 0.79) or air bronchograms (median Fleiss' κ = 0.72)). Intraobserver consistency was relatively low for intermediate LUS scores (e.g. LUS Score 1 median Fleiss' κ = 0.52). We therefore conclude that more distinct LUS findings (e.g., air bronchograms, subpleural consolidations) may be more suitable for disease monitoring, especially with more than one investigator and that training material used for LUS in point-of-care ultrasound (POCUS) should pay refined attention to areas such as B-line quantification and differentiation of intermediate LUS scores.


Subject(s)
COVID-19/diagnostic imaging , Lung/diagnostic imaging , Point-of-Care Systems , SARS-CoV-2 , COVID-19/therapy , Female , Humans , Male , Middle Aged , Monitoring, Physiologic , Observer Variation , Prospective Studies , Ultrasonography
2.
J Biomol Struct Dyn ; : 1-28, 2021 May 20.
Article in English | MEDLINE | ID: covidwho-1236146

ABSTRACT

The COVID-19 pandemic has severely destructed human life worldwide, with no suitable treatment until now. SARS-CoV-2 virus is unprecedented, resistance against number of therapeutics and spreading rapidly with high mortality, which warrants the need to discover new effective drugs to combat this situation. This current study is undertaken to explore the antiviral potential of marine algal compounds to inhibit the viral entry and its multiplication using computational analysis. Among the proven drug discovery targets of SARS-CoV-2, spike glycoprotein and 3-chymotrypsin-like protease are responsible for the virus attachment and viral genome replication in the host cell. In this study, the above-mentioned drug targets were docked with marine algal compounds (sulfated polysaccharides, polysaccharide derivatives and polyphenols) using molecular docking tools (AutoDockTools). The obtained results indicate that κ-carrageenan, laminarin, eckol, trifucol and ß-D-galactose are the top-ranking compounds showing better docking scores with SARS-CoV-2 targets, than the current experimental COVID-19 antiviral drugs like dexamethasone, remdesivir, favipiravir and MIV-150. Further, molecular dynamic simulation, ADMET and density functional theory calculations were evaluated to substantiate the findings. To the best of our knowledge, this is the first report on in silico analysis of aforesaid algal metabolites against SARS-CoV-2 targets. This study concludes that these metabolites can be curative for COVID-19 in the hour of need after further validations in in vitro and in vivo testings.Communicated by Ramaswamy H. Sarma.

3.
Nat Prod Res ; : 1-5, 2021 May 05.
Article in English | MEDLINE | ID: covidwho-1216556

ABSTRACT

Clinacanthus nutans has been reported to have many medicinal properties and it is traditionally used in treating viral lesions. This study aims to determine the molecular docking of C. nutans compounds detected by Gas Chromatography-Mass Spectrometry (GC-MS) with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 main protease) protein and its host receptor angiotensin-converting enzyme 2 (ACE2) protein using the AutoDock 4.2 tool. The drug-likeness and molecular docking analyses showed that fourteen compounds of C. nutans satisfied the Lipinski's rule of five and they exhibited good inhibitory effects against the SARS-Cov-2 main protease and ACE2 proteins. In addition, the glyceryl 2-linolenate compound was found to have the most potent binding affinities with both proteins. The results provide useful insights into the molecular inhibitory interactions of C. nutans compounds detected by GC-MS analysis with the targeted SARS-CoV-2 main protease and ACE2 protein.

4.
PLoS One ; 16(4): e0249450, 2021.
Article in English | MEDLINE | ID: covidwho-1167118

ABSTRACT

Coronavirus disease 2019 (COVID-19) has been spread out all over the world. Although a real-time reverse-transcription polymerase chain reaction (RT-PCR) test has been used as a primary diagnostic tool for COVID-19, the utility of CT based diagnostic tools have been suggested to improve the diagnostic accuracy and reliability. Herein we propose a semi-supervised deep neural network for an improved detection of COVID-19. The proposed method utilizes CT images in a supervised and unsupervised manner to improve the accuracy and robustness of COVID-19 diagnosis. Both labeled and unlabeled CT images are employed. Labeled CT images are used for supervised leaning. Unlabeled CT images are utilized for unsupervised learning in a way that the feature representations are invariant to perturbations in CT images. To systematically evaluate the proposed method, two COVID-19 CT datasets and three public CT datasets with no COVID-19 CT images are employed. In distinguishing COVID-19 from non-COVID-19 CT images, the proposed method achieves an overall accuracy of 99.83%, sensitivity of 0.9286, specificity of 0.9832, and positive predictive value (PPV) of 0.9192. The results are consistent between the COVID-19 challenge dataset and the public CT datasets. For discriminating between COVID-19 and common pneumonia CT images, the proposed method obtains 97.32% accuracy, 0.9971 sensitivity, 0.9598 specificity, and 0.9326 PPV. Moreover, the comparative experiments with respect to supervised learning and training strategies demonstrate that the proposed method is able to improve the diagnostic accuracy and robustness without exhaustive labeling. The proposed semi-supervised method, exploiting both supervised and unsupervised learning, facilitates an accurate and reliable diagnosis for COVID-19, leading to an improved patient care and management.


Subject(s)
COVID-19/diagnostic imaging , Neural Networks, Computer , Supervised Machine Learning , Thorax , Tomography, X-Ray Computed , Algorithms , Datasets as Topic , Humans , Thorax/diagnostic imaging , Thorax/pathology
5.
Risk Manag Healthc Policy ; 14: 869-873, 2021.
Article in English | MEDLINE | ID: covidwho-1140605

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused extreme challenges for the healthcare system. Medical masks have been proven to effectively block disease transmission. Radiotherapeutic departments are at unique risk for disease exposure with the repeated daily treatment schedule. A protocol of mask wearing during daily treatment was established, and the effect of wearing medical masks on dosimetry during proton beam therapy (PBT) was validated. METHODS: A department protocol of medical mask wearing was initiated after the COVID-19 pandemic. Medical masks that were made under standardized specification and regulation were obtained for analyses. The physical and dosimetric characteristics of these medical masks were measured by different proton energies using commercialized measurement tools. RESULTS: Patients and staff were able to adopt the protocol on a weekly basis, and no adverse events were reported. The average physical thickness of a single piece of medical mask was 0.5 mm with a water equivalent thickness (WET) of 0.1 mm. CONCLUSION: Our study revealed that mask wearing for patients undergoing daily radiotherapy is feasible and can provide basic protection for patients and staff. The impact of mask wearing on dosimetry was only 0.1 mm in WET, which has no impact on clinical PBT treatment. A medical mask-wearing policy can be applied safely without dosimetric concerns and should be considered as a standard practice for PBT centers during the COVID-19 pandemic.

6.
Sensors (Basel) ; 21(5)2021 Mar 07.
Article in English | MEDLINE | ID: covidwho-1134223

ABSTRACT

BACKGROUND: In the dental field, digital technology has created new opportunities for orthodontists to integrate their clinical practice, and for patients to collect information about orthodontics and their treatment, which is called "teledentistry." Dental monitoring (DM) is a recently introduced orthodontic application that combines safe teledentistry with artificial intelligence (AI) using a knowledge-based algorithm, allowing an accurate semi-automatic monitoring of the treatment. Dental Monitoring is the world's first SaaS (Software as a Service) application designed for remote monitoring of dental treatment, developed in Paris, France, with Philippe Salah as the Co-founder and CEO. CASES PRESENTATION: This report describes two cases in which DM system was essential to achieve the control of certain movements: it was possible to follow the movement, even if complex, such as the anterior cross of an adult patient and a lack of space in the canine of the growing patient. The software analyzed the fit and retention of the aligner, thus ensuring correct biomechanics. They were treated during the COVID-19 pandemic lockdown with aligners. The first case is a growing patient who was monitored during an interceptive orthodontic treatment to manage a retained upper canine. The second case is an adult patient forced to finalize his treatment of upper lateral incisor crossbite. The software analyzed the fit and retention of the aligner, thus ensuring correct biomechanics. CONCLUSIONS: DM system appears to be a promising method, useful for improving the interaction between doctor and patient, generally acceptable and useful to patients, even in critical clinical situations, at least in cases with optimal compliance and ability to use the tool properly.


Subject(s)
Artificial Intelligence , Orthodontic Appliance Design , Software , Telemedicine , Tooth Movement Techniques , Adult , COVID-19 , Communicable Disease Control , France , Humans , Pandemics
7.
Int J Mol Sci ; 22(5)2021 Mar 08.
Article in English | MEDLINE | ID: covidwho-1134168

ABSTRACT

The fruit fly, Drosophila melanogaster, has been used to understand fundamental principles of genetics and biology for over a century. Drosophila is now also considered an essential tool to study mechanisms underlying numerous human genetic diseases. In this review, we will discuss how flies can be used to deepen our knowledge of infectious disease mechanisms in vivo. Flies make effective and applicable models for studying host-pathogen interactions thanks to their highly conserved innate immune systems and cellular processes commonly hijacked by pathogens. Drosophila researchers also possess the most powerful, rapid, and versatile tools for genetic manipulation in multicellular organisms. This allows for robust experiments in which specific pathogenic proteins can be expressed either one at a time or in conjunction with each other to dissect the molecular functions of each virulent factor in a cell-type-specific manner. Well documented phenotypes allow large genetic and pharmacological screens to be performed with relative ease using huge collections of mutant and transgenic strains that are publicly available. These factors combine to make Drosophila a powerful tool for dissecting out host-pathogen interactions as well as a tool to better understand how we can treat infectious diseases that pose risks to public health, including COVID-19, caused by SARS-CoV-2.


Subject(s)
Communicable Diseases/immunology , Communicable Diseases/metabolism , Drosophila melanogaster/immunology , Drosophila melanogaster/metabolism , Animals , Communicable Diseases/microbiology , Communicable Diseases/virology , Drosophila melanogaster/microbiology , Drosophila melanogaster/virology , Host-Pathogen Interactions , Immunity, Innate , Signal Transduction , Virulence Factors/metabolism
8.
Sci Adv ; 7(10)2021 03.
Article in English | MEDLINE | ID: covidwho-1119271

ABSTRACT

Face masks prevent transmission of infectious respiratory diseases by blocking large droplets and aerosols during exhalation or inhalation. While three-layer masks are generally advised, many commonly available or makeshift masks contain single or double layers. Using carefully designed experiments involving high-speed imaging along with physics-based analysis, we show that high-momentum, large-sized (>250 micrometer) surrogate cough droplets can penetrate single- or double-layer mask material to a significant extent. The penetrated droplets can atomize into numerous much smaller (<100 micrometer) droplets, which could remain airborne for a significant time. The possibility of secondary atomization of high-momentum cough droplets by hydrodynamic focusing and extrusion through the microscale pores in the fibrous network of the single/double-layer mask material needs to be considered in determining mask efficacy. Three-layer masks can effectively block these droplets and thus could be ubiquitously used as a key tool against COVID-19 or similar respiratory diseases.


Subject(s)
Aerosols , Cough/pathology , Masks , COVID-19/diagnosis , COVID-19/virology , Humans , Image Processing, Computer-Assisted , Particle Size , Probability , SARS-CoV-2/physiology , Viral Load
9.
Netw Model Anal Health Inform Bioinform ; 10(1): 14, 2021.
Article in English | MEDLINE | ID: covidwho-1101018

ABSTRACT

The main aim of the paper was to determine bioactive compounds in Pleione maculata extracts using gas chromatographic technique and to investigate their drug-likeness potential using molecular docking algorithm and ADME studies on the recent intractable disease, for example, SARS-CoV-2. Pleione maculata sample was prepared for GC-MS analysis. The peak components were identified based on the NIST Library. Molecular docking was performed using PatchDock, and energy refinement was carried out using the FireDock algorithm followed by drug-likeness analysis using the SwissADME tool. The mass spectrum revealed various pharmacologically important compounds and novel compounds 8-oxatetracyclo{5.2.1.1(2,6). 1(4,10)}dodecane, 7-tert-butyl-1,9,9-trimeth, docosane, 2,4-dimethyl, kryptogenin 2,4-dinitrophenyl hydrazine, and N-decyl-alpha,D-2-deoxyglycoside which are reported for the first time. Molecular docking using PatchDock illustrates GC-MS compounds Nor-diazepam,3-{N-hydroxymethyl}aminocarbonyloxy a good docking and high binding affinity with atomic contact energy -10.95 kcal/mol against SARS-CoV-2 spike protein S2 subunit. ADME analysis predicts Nor-diazepam,3-{N-hydroxymethyl}aminocarbonyloxy and andrographolide showed very high drug-likeness parameters with no metabolism disturbances. The random control antiviral drug arabidiol revealed a lower binding affinity and lower solubility compared to bioactive compounds of P. maculata. The study depicts the first and novel report on various pharmaceutical important GC-MS bioactive compounds and molecular docking study on Pleione maculata having potential against various intractable diseases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13721-020-00276-1.

10.
Health Technol (Berl) ; : 1-11, 2021 Feb 14.
Article in English | MEDLINE | ID: covidwho-1092850

ABSTRACT

Expert system is an artificial intelligence based system that imitates the decision making ability of human and it is used as the diagnostic tool for many diseases including diabetes mellitus, COVID-19, cancers, coronary artery disease (CAD), among other diseases. Even though CAD is globally one of the deadliest diseases and it is not well known in Nigeria, it causes many deaths as such in 2014, 53,836 or 2.82% of total deaths in Nigeria resulted from the CAD. In this study, fuzzy based expert system for diagnosis of CAD is developed in order to provide the complementary diagnostic tools for diagnosis of CAD's patients in Nigeria. The improved C4.5 data mining algorithm is used to transfer the knowledge of human expert to the knowledge base on the expert system instead of using conventional techniques such as interviews, questionnaires, etc. Taken together, the performance evaluation system was carried out, and the system has an overall accuracy, sensitivity and specificity of 94.55%, 95.35% and 95.00% respectively; which show that, the system is reliable and capable of diagnosing both negative and positive cases of CAD patients efficiently.

11.
Molecules ; 26(4)2021 Feb 20.
Article in English | MEDLINE | ID: covidwho-1090311

ABSTRACT

The ongoing coronavirus pandemic has been a burden on the worldwide population, with mass fatalities and devastating socioeconomic consequences. It has particularly drawn attention to the lack of approved small-molecule drugs to inhibit SARS coronaviruses. Importantly, lessons learned from the SARS outbreak of 2002-2004, caused by severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), can be applied to current drug discovery ventures. SARS-CoV-1 and SARS-CoV-2 both possess two cysteine proteases, the main protease (Mpro) and the papain-like protease (PLpro), which play a significant role in facilitating viral replication, and are important drug targets. The non-covalent inhibitor, GRL-0617, which was found to inhibit replication of SARS-CoV-1, and more recently SARS-CoV-2, is the only PLpro inhibitor co-crystallised with the recently solved SARS-CoV-2 PLpro crystal structure. Therefore, the GRL-0617 structural template and pharmacophore features are instrumental in the design and development of more potent PLpro inhibitors. In this work, we conducted scaffold hopping using GRL-0617 as a reference to screen over 339,000 ligands in the chemical space using the ChemDiv, MayBridge, and Enamine screening libraries. Twenty-four distinct scaffolds with structural and electrostatic similarity to GRL-0617 were obtained. These proceeded to molecular docking against PLpro using the AutoDock tools. Of two compounds that showed the most favourable predicted binding affinities to the target site, as well as comparable protein-ligand interactions to GRL-0617, one was chosen for further analogue-based work. Twenty-seven analogues of this compound were further docked against the PLpro, which resulted in two additional hits with promising docking profiles. Our in silico pipeline consisted of an integrative four-step approach: (1) ligand-based virtual screening (scaffold-hopping), (2) molecular docking, (3) an analogue search, and, (4) evaluation of scaffold drug-likeness, to identify promising scaffolds and eliminate those with undesirable properties. Overall, we present four novel, and lipophilic, scaffolds obtained from an exhaustive search of diverse and uncharted regions of chemical space, which may be further explored in vitro through structure-activity relationship (SAR) studies in the search for more potent inhibitors. Furthermore, these scaffolds were predicted to have fewer off-target interactions than GRL-0617. Lastly, to our knowledge, this work contains the largest ligand-based virtual screen performed against GRL-0617.


Subject(s)
Antiviral Agents/chemistry , COVID-19/enzymology , Coronavirus 3C Proteases , Cysteine Proteinase Inhibitors/chemistry , Molecular Docking Simulation , SARS-CoV-2/enzymology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/chemistry , Crystallography, X-Ray , Cysteine Proteinase Inhibitors/therapeutic use , Drug Evaluation, Preclinical , Humans
12.
Immunobiology ; 226(1): 152021, 2021 01.
Article in English | MEDLINE | ID: covidwho-908903

ABSTRACT

SARS-CoV-2 is a highly contagious virus that has caused serious health crisis world-wide resulting into a pandemic situation. As per the literature, the SARS-CoV-2 is known to exploit humanACE2 receptors (similar toprevious SARS-CoV-1) for gaining entry into the host cell for invasion, infection, multiplication and pathogenesis. However, considering the higher infectivity of SARS-CoV-2 along with the complex etiology and pathophysiological outcomes seen in COVID-19 patients, it seems that there may be an alternate receptor for SARS-CoV-2. I performed comparative protein sequence analysis, database based gene expression profiling, bioinformatics based molecular docking using authentic tools and techniques for unveiling the molecular basis of high infectivity of SARS-CoV-2 as compared to previous known coronaviruses. My study revealed that SARS-CoV-2 (previously known as 2019-nCoV) harbors a RGD motif in its receptor binding domain (RBD) and the motif is absent in all other previously known SARS-CoVs. The RGD motif is well known for its role in cell-attachment and cell-adhesion. My hypothesis is that the SARS-CoV-2 may be (via RGD) exploiting integrins, that have high expression in lungs and all other vital organs, for invading host cells. However, an experimental verification is required. The expression of ACE2, which is a known receptor for SARS-CoV-2, was found to be negligible in lungs. I assume that higher infectivity of SARS-CoV-2 could be due to this RGD-integrin mediated acquired cell-adhesive property. Gene expression profiling revealed that expression of integrins is significantly high in lung cells, in particular αvß6, α5ß1, αvß8 and an ECM protein, ICAM1. The molecular docking experiment showed the RBD of spike protein binds with integrins precisely at RGD motif in a similar manner as a synthetic RGD peptide binds to integrins as found by other researchers. SARS-CoV-2 spike protein has a number of phosphorylation sites that can induce cAMP, PKC, Tyr signaling pathways. These pathways either activate calcium ion channels or get activated by calcium. In fact, integrins have calcium & metal binding sites that were predicted around and in vicinity of RGD-integrin docking site in our analysis which suggests that RGD-integrins interaction possibly occurs in calcium-dependent manner. The higher expression of integrins in lungs along with their previously known high binding affinity (~KD = 4.0 nM) for virus RGD motif could serve as a possible explanation for high infectivity of SARS-CoV-2. On the contrary, human ACE2 has lower expression in lungs and its high binding affinity (~KD = 15 nM) for spike RBD alone could not manifest significant virus-host attachment. This suggests that besides human ACE2, an additional or alternate receptor for SARS-CoV-2 is likely to exist. A highly relevant evidence never reported earlier which corroborate in favor of RGD-integrins mediated virus-host attachment is an unleashed cytokine storm which causes due to activation of TNF-α and IL-6 activation; and integrins role in their activation is also well established. Altogether, the current study has highlighted possible role of calcium and other divalent ions in RGD-integrins interaction for virus invasion into host cells and suggested that lowering divalent ion in lungs could avert virus-host cells attachment.


Subject(s)
COVID-19/virology , Calcium/metabolism , Chelation Therapy , Edetic Acid/therapeutic use , Integrins/metabolism , Receptors, Immunologic/metabolism , Receptors, Peptide/metabolism , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Binding Sites/genetics , COVID-19/drug therapy , Calcium Channels/metabolism , Gene Expression Profiling , Humans , Integrins/chemistry , Intercellular Adhesion Molecule-1/metabolism , Interleukin-6/metabolism , Lung/metabolism , Molecular Docking Simulation , Oligopeptides/chemistry , Oligopeptides/metabolism , Protein Binding , Receptors, Virus/metabolism , SARS-CoV-2/metabolism , Sequence Alignment , Signal Transduction/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Tumor Necrosis Factor-alpha/metabolism , Virus Attachment
13.
Res Sq ; 2020 Jul 16.
Article in English | MEDLINE | ID: covidwho-671168

ABSTRACT

Background : The online teaching demand has increased tremendously to promote the implementation of online teaching-leaning system to meet the need of students during the outbreaks of emerging infectious disease. This study aims to explore whether the pandemic of COVID-19, which requires universities to rapidly offer online learning, will affect attitudes about online education for undergraduate health sciences students. Also, it investigates the barriers for using online tools. Method : A cross-sectional survey using online social media was used to recruit eligible participants. The data for this study were focused on students' experiences utilizing an online education method offered by the Jordanian government universities. This study is utilizing newly developed measuring tools that are expected to enable students to evaluate online teaching in terms of their own learning progress. Results : A total of 1,210 participants agreed to complete the online survey questionnaire. The mean score preparedness and attitude toward online education was average. The majority of students agreed that online courses helped assign reading and homework time better than on-campus approach (75.0%) and felt comfortable to actively communicate with my classmates and instructors online. Zoom and eLearning were the most common online platforms utilized by students. The geographic locations, lack of past experience on using online tools, and lack of past experience on using online tools were identified by students as the main barrier to online educations. Conclusions : Although the pandemic of COVID-19 appeared as uncommon catalyst for promoting eLearning, further research is needed to assess whether learners are ready and willing to make greater use of online education to obtain high quality teaching and learning opportunities, which could totally change educators' and students' attitudes and impression, and subsequently the general themes of online education.

14.
Comb Chem High Throughput Screen ; 25(3): 392-400, 2022.
Article in English | MEDLINE | ID: covidwho-740472

ABSTRACT

AIM AND OBJECTIVE: Aim and Objective: Sequence analysis is one of the foundations in bioinformatics. It is widely used to find out the feature metrics hidden in the sequence. Otherwise, the graphical representation of the biologic sequence is an important tool for sequencing analysis. This study is undertaken to find out a new graphical representation of biosequences. MATERIALS AND METHODS: The transition probability is used to describe amino acid combinations of protein sequences. The combinations are composed of amino acids directly adjacent to each other or separated by multiple amino acids. The transition probability graph is built up by the transition probabilities of amino acid combinations. Next, a map is defined as a representation from the transition probability graph to transition probability vector by the k-order transition probability graph. Transition entropy vectors are developed by the transition probability vector and information entropy. Finally, the proposed method is applied to two separate applications, 499 HA genes of H1N1, and 95 coronaviruses. RESULTS: By constructing a phylogenetic tree, it was found that the results of each application are consistent with other studies. CONCLUSION: The graphical representation proposed in this article is a practical and correct method.


Subject(s)
Influenza A Virus, H1N1 Subtype , Algorithms , Amino Acid Sequence , Entropy , Phylogeny , Probability
15.
Curr Opin Crit Care ; 26(5): 489-499, 2020 10.
Article in English | MEDLINE | ID: covidwho-708833

ABSTRACT

PURPOSE OF REVIEW: Given the growing body of critical care clinical research publications, core outcome sets (COSs) are important to help mitigate heterogeneity in outcomes assessed and measurement instruments used, and have potential to reduce research waste. This article provides an update on COS projects in critical care medicine, and related resources and tools for COS developers. RECENT FINDINGS: We identified 28 unique COS projects, of which 15 have published results as of May 2020. COS topics relevant to critical care medicine include mechanical ventilation, cardiology, stroke, rehabilitation, and long-term outcomes (LTOs) after critical illness. There are four COS projects for coronavirus disease 2019 (COVID-19), with a 'meta-COS' summarizing common outcomes across these projects. To help facilitate COS development, there are existing resources, standards, guidelines, and tools available from the Core Outcome Measures in Effectiveness Trials Initiative (www.comet-initiative.org/) and the National Institutes of Health-funded Improve LTO project (www.improvelto.com/). SUMMARY: Many COS projects have been completed in critical care, with more on-going COS projects, including foci from across the spectrum of acute critical care, COVID-19, critical care rehabilitation, and patient recovery and LTOs. Extensive resources are accessible to help facilitate rigorous COS development.


Subject(s)
Coronavirus Infections , Critical Illness , Pandemics , Pneumonia, Viral , Research Design , Betacoronavirus , COVID-19 , Cardiology , Delphi Technique , Humans , Respiration, Artificial , SARS-CoV-2 , Stroke Rehabilitation
16.
J Transl Med ; 18(1): 278, 2020 07 09.
Article in English | MEDLINE | ID: covidwho-652087

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome (SARS) has been initiating pandemics since the beginning of the century. In December 2019, the world was hit again by a devastating SARS episode that has so far infected almost four million individuals worldwide, with over 200,000 fatalities having already occurred by mid-April 2020, and the infection rate continues to grow exponentially. SARS coronavirus 2 (SARS-CoV-2) is a single stranded RNA pathogen which is characterised by a high mutation rate. It is vital to explore the mutagenic capability of the viral genome that enables SARS-CoV-2 to rapidly jump from one host immunity to another and adapt to the genetic pool of local populations. METHODS: For this study, we analysed 2301 complete viral sequences reported from SARS-CoV-2 infected patients. SARS-CoV-2 host genomes were collected from The Global Initiative on Sharing All Influenza Data (GISAID) database containing 9 genomes from pangolin-CoV origin and 3 genomes from bat-CoV origin, Wuhan SARS-CoV2 reference genome was collected from GeneBank database. The Multiple sequence alignment tool, Clustal Omega was used for genomic sequence alignment. The viral replicating enzyme, 3-chymotrypsin-like cysteine protease (3CLpro) that plays a key role in its pathogenicity was used to assess its affinity with pharmacological inhibitors and repurposed drugs such as anti-viral flavones, biflavanoids, anti-malarial drugs and vitamin supplements. RESULTS: Our results demonstrate that bat-CoV shares > 96% similar identity, while pangolin-CoV shares 85.98% identity with Wuhan SARS-CoV-2 genome. This in-depth analysis has identified 12 novel recurrent mutations in South American and African viral genomes out of which 3 were unique in South America, 4 unique in Africa and 5 were present in-patient isolates from both populations. Using state of the art in silico approaches, this study further investigates the interaction of repurposed drugs with the SARS-CoV-2 3CLpro enzyme, which regulates viral replication machinery. CONCLUSIONS: Overall, this study provides insights into the evolving mutations, with implications to understand viral pathogenicity and possible new strategies for repurposing compounds to combat the nCovid-19 pandemic.


Subject(s)
Betacoronavirus/enzymology , Computer Simulation , Coronavirus Infections/virology , Cysteine Endopeptidases/metabolism , DNA Replication , Drug Repositioning , Geography , Pneumonia, Viral/virology , Viral Nonstructural Proteins/metabolism , Betacoronavirus/genetics , COVID-19 , Coronavirus 3C Proteases , Evolution, Molecular , Genome, Viral , Humans , Molecular Docking Simulation , Mutation/genetics , Mutation Rate , Pandemics , Phylogeny , SARS-CoV-2 , Virus Assembly
17.
Heliyon ; 6(7): e04405, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-634144

ABSTRACT

Early diagnosis of SARS-CoV-2 infected patients is essential to control the dynamics of the COVID-19 pandemic. We develop a rapid and accurate one-step multiplex TaqMan probe-based real-time RT-PCR assay, along with a computational tool to systematically analyse the data. Our assay could detect to a limit of 15 copies of SARS-CoV-2 transcripts-based on experiments performed by spiking total human RNA with in vitro synthesized viral transcripts. The assay was evaluated by performing 184 validations for the SARS-CoV-2 Nucleocapsid gene and human RNase P as an internal control reference gene with dilutions ranging from 1-100 ng for human RNA on a cohort of 26 clinical samples. 5 of 26 patients were confirmed to be infected with SARS-CoV-2, while 21 tested negative, consistent with the standards. The accuracy of the assay was found to be 100% sensitive and 100% specific based on the 26 clinical samples that need to be further verified using a large number of clinical samples. In summary, we present a rapid, easy to implement real-time PCR based assay with automated analysis using a novel COVID qPCR Analyzer tool with graphical user interface (GUI) to analyze the raw qRT-PCR data in an unbiased manner at a cost of under $3 per reaction and turnaround time of less than 2h, to enable in-house SARS-CoV-2 testing across laboratories.

18.
J Chin Med Assoc ; 83(6): 537-543, 2020 06.
Article in English | MEDLINE | ID: covidwho-601886

ABSTRACT

BACKGROUND: China announced an outbreak of new coronavirus in the city of Wuhan on December 31, 2019; lash to now, the virus transmission has become pandemic worldwide. Severe cases from the Huanan Seafood Wholesale market in Wuhan were confirmed pneumonia with a novel coronavirus (2019-nCoV). Understanding the molecular mechanisms of genome selection and packaging is critical for developing antiviral strategies. Thus, we defined the correlation in 10 severe acute respiratory syndrome coronavirus (SARS-CoV2) sequences from different countries to analyze the genomic patterns of disease origin and evolution aiming for developing new control pandemic processes. METHODS: We apply genomic analysis to observe SARS-CoV2 sequences from GenBank (http://www.ncbi.nim.nih.gov/genebank/): MN 908947 (China, C1), MN985325 (USA: WA, UW), MN996527 (China, C2), MT007544 (Australia: Victoria, A1), MT027064 (USA: CA, UC), MT039890 (South Korea, K1), MT066175 (Taiwan, T1), MT066176 (Taiwan, T2), LC528232 (Japan, J1), and LC528233 (Japan, J2) for genomic sequence alignment analysis. Multiple Sequence Alignment by Clustalw (https://www.genome.jp/tools-bin/clustalw) web service is applied as our alignment tool. RESULTS: We analyzed 10 sequences from the National Center for Biotechnology Information (NCBI) database by genome alignment and found no difference in amino acid sequences within M and N proteins. There are two amino acid variances in the spike (S) protein region. One mutation found from the South Korea sequence is verified. Two possible "L" and "S" SNPs found in ORF1ab and ORF8 regions are detected. CONCLUSION: We performed genomic analysis and comparative multiple sequences of SARS-CoV2. Studies about the biological symptoms of SARS-CoV2 in clinic animals and humans will manipulate an understanding on the origin of pandemic crisis.


Subject(s)
Betacoronavirus/genetics , Genome, Viral , Amino Acid Sequence , Polymorphism, Single Nucleotide , SARS-CoV-2 , Sequence Alignment , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics
19.
J Intern Med ; 288(2): 192-206, 2020 08.
Article in English | MEDLINE | ID: covidwho-141690

ABSTRACT

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2, a novel coronavirus from the same family as SARS-CoV and Middle East respiratory syndrome coronavirus, has spread worldwide leading the World Health Organization to declare a pandemic. The disease caused by SARS-CoV-2, coronavirus disease 2019 (COVID-19), presents flu-like symptoms which can become serious in high-risk individuals. Here, we provide an overview of the known clinical features and treatment options for COVID-19. We carried out a systematic literature search using the main online databases (PubMed, Google Scholar, MEDLINE, UpToDate, Embase and Web of Science) with the following keywords: 'COVID-19', '2019-nCoV', 'coronavirus' and 'SARS-CoV-2'. We included publications from 1 January 2019 to 3 April 2020 which focused on clinical features and treatments. We found that infection is transmitted from human to human and through contact with contaminated environmental surfaces. Hand hygiene is fundamental to prevent contamination. Wearing personal protective equipment is recommended in specific environments. The main symptoms of COVID-19 are fever, cough, fatigue, slight dyspnoea, sore throat, headache, conjunctivitis and gastrointestinal issues. Real-time PCR is used as a diagnostic tool using nasal swab, tracheal aspirate or bronchoalveolar lavage samples. Computed tomography findings are important for both diagnosis and follow-up. To date, there is no evidence of any effective treatment for COVID-19. The main therapies being used to treat the disease are antiviral drugs, chloroquine/hydroxychloroquine and respiratory therapy. In conclusion, although many therapies have been proposed, quarantine is the only intervention that appears to be effective in decreasing the contagion rate. Specifically designed randomized clinical trials are needed to determine the most appropriate evidence-based treatment modality.


Subject(s)
Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Antiviral Agents/therapeutic use , Betacoronavirus , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Humans , Hydroxychloroquine/therapeutic use , Lung/diagnostic imaging , Pandemics , Patient Isolation , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Respiratory Therapy , SARS-CoV-2
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