The pathogenetic influence of smoking on SARS-CoV-2 infection: Integrative transcriptome and regulomics analysis of lung epithelial cells.

Corona virus disease (COVID-19) has been emerged as pandemic infectious disease. The recent epidemiological data suggest that the smokers are more vulnerable to infection with COVID-19; however, the influence of smoking (SMK) on the COVID-19 infected patients and the mortality is not known yet. In this study, we aimed to discern the influence of SMK on COVID-19 infected patients utilizing the transcriptomics data of COVID-19 infected lung epithelial cells and transcriptomics data smoking matched with controls from lung epithelial cells. The bioinformatics based analysis revealed the molecular insights into the level of transcriptional changes and pathways which are important to identify the impact of smoking on COVID-19 infection and prevalence. We compared differentially expressed genes (DEGs) between COVID-19 and SMK and 59 DEGs were identified as consistently dysregulated at transcriptomics levels. The correlation network analyses were constructed for these common genes using WGCNA R package to see the relationship among these genes. Integration of DEGs with network analysis (protein-protein interaction) showed the presence of 9 hub proteins as key so called "candidate hub proteins" overlapped between COVID-19 patients and SMK. The Gene Ontology and pathways analysis demonstrated the enrichment of inflammatory pathway such as IL-17 signaling pathway, Interleukin-6 signaling, TNF signaling pathway and MAPK1/MAPK3 signaling pathways that might be the therapeutic targets in COVID-19 for smoking persons. The identified genes, pathways, hubs genes, and their regulators might be considered for establishment of key genes and drug targets for SMK and COVID-19.

The pathogenetic influence of smoking on SARS-CoV-2 infection: Integrative transcriptome and regulomics analysis of lung epithelial cells

Corona virus disease (COVID-19) has been emerged as pandemic infectious disease. The recent epidemiological data suggest that the smokers are more vulnerable to infection with COVID-19;however, the influence of smoking (SMK) on the COVID-19 infected patients and the mortality is not known yet. In this study, we aimed to discern the influence of SMK on COVID-19 infected patients utilizing the transcriptomics data of COVID-19 infected lung epitheial cells and transcriptomics data smoking matched with controls from lung epithelial cells. The bioinformatics based analysis revealed the molecular insights into the level of transcriptional changes and pathways which are important to identify the impact of smoking on COVID-19 infection and prevalence. We compared differentially expressed genes (DEGs) between COVID-19 and SMK and 59 DEGs were identified as consistently dysregulated at transcripomics levels. The correlation network analyses were constructed for these common genes using WGCNA R package to see the relationship among these genes. Integration of DEGs with network analysis (protein-protein interaction) showed the presence of 9 hub proteins as key so called ”candidate hub proteins” overlapped between COVID-19 patients and SMK. The Gene Ontology and pathways analysis demonstrated the enrichment of inflammatory pathway such as IL-17 signaling pathway, Interleukin-6 signaling, TNF signaling pathway and MAPK1/MAPK3 signaling pathways that might be the therapeutic targets in COVID-19 for smoking persons. The identified genes, pathways, hubs genes, and their regulators might be considered for establishment of key genes and drug targets for SMK and COVID-19.

Adverse Effects of COVID-19 Vaccination: Machine Learning and Statistical Approach to Identify and Classify Incidences of Morbidity and Postvaccination Reactogenicity.

Good vaccine safety and reliability are essential for successfully countering infectious disease spread. A small but significant number of adverse reactions to COVID-19 vaccines have been reported. Here, we aim to identify possible common factors in such adverse reactions to enable strategies that reduce the incidence of such reactions by using patient data to classify and characterise those at risk. We examined patient medical histories and data documenting postvaccination effects and outcomes. The data analyses were conducted using a range of statistical approaches followed by a series of machine learning classification algorithms. In most cases, a group of similar features was significantly associated with poor patient reactions. These included patient prior illnesses, admission to hospitals and SARS-CoV-2 reinfection. The analyses indicated that patient age, gender, taking other medications, type-2 diabetes, hypertension, allergic history and heart disease are the most significant pre-existing factors associated with the risk of poor outcome. In addition, long duration of hospital treatments, dyspnoea, various kinds of pain, headache, cough, asthenia, and physical disability were the most significant clinical predictors. The machine learning classifiers that are trained with medical history were also able to predict patients with complication-free vaccination and have an accuracy score above 90%. Our study identifies profiles of individuals that may need extra monitoring and care (e.g., vaccination at a location with access to comprehensive clinical support) to reduce negative outcomes through classification approaches.

An integrated in-silico Pharmaco-BioInformatics approaches to identify synergistic effects of COVID-19 to HIV patients.

BACKGROUND: With high inflammatory states from both COVID-19 and HIV conditions further result in complications. The ongoing confrontation between these two viral infections can be avoided by adopting suitable management measures. PURPOSE: The aim of this study was to figure out the pharmacological mechanism behind apigenin's role in the synergetic effects of COVID-19 to the progression of HIV patients. METHOD: We employed computer-aided methods to uncover similar biological targets and signaling pathways associated with COVID-19 and HIV, along with bioinformatics and network pharmacology techniques to assess the synergetic effects of apigenin on COVID-19 to the progression of HIV, as well as pharmacokinetics analysis to examine apigenin's safety in the human body. RESULT: Stress-responsive, membrane receptor, and induction pathways were mostly involved in gene ontology (GO) pathways, whereas apoptosis and inflammatory pathways were significantly associated in the Kyoto encyclopedia of genes and genomes (KEGG). The top 20 hub genes were detected utilizing the shortest path ranked by degree method and protein-protein interaction (PPI), as well as molecular docking and molecular dynamics simulation were performed, revealing apigenin's strong interaction with hub proteins (MAPK3, RELA, MAPK1, EP300, and AKT1). Moreover, the pharmacokinetic features of apigenin revealed that it is an effective therapeutic agent with minimal adverse effects, for instance, hepatoxicity. CONCLUSION: Synergetic effects of COVID-19 on the progression of HIV may still be a danger to global public health. Consequently, advanced solutions are required to give valid information regarding apigenin as a suitable therapeutic agent for the management of COVID-19 and HIV synergetic effects. However, the findings have yet to be confirmed in patients, suggesting more in vitro and in vivo studies.

Development of an in silico multi-epitope vaccine against SARS-COV-2 by précised immune-informatics approaches.

The coronavirus family has been infecting the human population for the past two decades, but the ongoing coronavirus called SARS-CoV-2 has posed an enigmatic challenge to global public health security. Since last year, the mutagenic quality of this virus is causing changes to its genetic material. To prevent those situations, the FDA approved some emergency vaccines but there is no assurance that these will function properly in the complex human body system. In point of view, a short but efficient effort has made in this study to develop an immune epitope-based therapy for the rapid exploitation of SARS-CoV-2 by applying in silico structural biology and advancing immune information strategies. The antigenic epitopes were screened from the Surface, Membrane, Envelope proteins of SARS-CoV-2 and passed through several immunological filters to determine the best possible one. According to this, 7CD4+, 10CD8+ and 5 B-cell epitopes were found to be prominent, antigenic, immunogenic, and most importantly, highly conserved among 128 Bangladeshi and 110 other infected countries SARS-CoV-2 variants. After that, the selected epitopes and adjuvant were linked to finalize the multi-epitope vaccine by appropriate linkers. The immune simulation disclosed that the engineered vaccine could activate both humoral and innate immune responses. For the prediction of an effective binding, molecular docking was carried out between the vaccine and immunological receptors (TLRs). Strong binding affinity and good docking scores clarified the stringency of the vaccines. Furthermore, MD simulation was performed within the highest binding affinity complex to observe the stability. Codon optimization and other physicochemical properties revealed that the vaccine would be suitable for a higher expression at cloning level. So, monitoring the overall in silico assessment, we anticipated that our engineered vaccine would be a plausible prevention against COVID-19.

DTLCx: An Improved ResNet Architecture to Classify Normal and Conventional Pneumonia Cases from COVID-19 Instances with Grad-CAM-Based Superimposed Visualization Utilizing Chest X-ray Images.

COVID-19 is a severe respiratory contagious disease that has now spread all over the world. COVID-19 has terribly impacted public health, daily lives and the global economy. Although some developed countries have advanced well in detecting and bearing this coronavirus, most developing countries are having difficulty in detecting COVID-19 cases for the mass population. In many countries, there is a scarcity of COVID-19 testing kits and other resources due to the increasing rate of COVID-19 infections. Therefore, this deficit of testing resources and the increasing figure of daily cases encouraged us to improve a deep learning model to aid clinicians, radiologists and provide timely assistance to patients. In this article, an efficient deep learning-based model to detect COVID-19 cases that utilizes a chest X-ray images dataset has been proposed and investigated. The proposed model is developed based on ResNet50V2 architecture. The base architecture of ResNet50V2 is concatenated with six extra layers to make the model more robust and efficient. Finally, a Grad-CAM-based discriminative localization is used to readily interpret the detection of radiological images. Two datasets were gathered from different sources that are publicly available with class labels: normal, confirmed COVID-19, bacterial pneumonia and viral pneumonia cases. Our proposed model obtained a comprehensive accuracy of 99.51% for four-class cases (COVID-19/normal/bacterial pneumonia/viral pneumonia) on Dataset-2, 96.52% for the cases with three classes (normal/ COVID-19/bacterial pneumonia) and 99.13% for the cases with two classes (COVID-19/normal) on Dataset-1. The accuracy level of the proposed model might motivate radiologists to rapidly detect and diagnose COVID-19 cases.

Feature fusion based VGGFusionNet model to detect COVID-19 patients utilizing computed tomography scan images.

COVID-19 is one of the most life-threatening and dangerous diseases caused by the novel Coronavirus, which has already afflicted a larger human community worldwide. This pandemic disease recovery is possible if detected in the early stage. We proposed an automated deep learning approach from Computed Tomography (CT) scan images to detect COVID-19 positive patients by following a four-phase paradigm for COVID-19 detection: preprocess the CT scan images; remove noise from test image by using anisotropic diffusion techniques; make a different segment for the preprocessed images; and train and test COVID-19 detection using Convolutional Neural Network (CNN) models. This study employed well-known pre-trained models, including AlexNet, ResNet50, VGG16 and VGG19 to evaluate experiments. 80% of images are used to train the network in the detection process, while the remaining 20% are used to test it. The result of the experiment evaluation confirmed that the VGG19 pre-trained CNN model achieved better accuracy (98.06%). We used 4861 real-life COVID-19 CT images for experiment purposes, including 3068 positive and 1793 negative images. These images were acquired from a hospital in Sao Paulo, Brazil and two other different data sources. Our proposed method revealed very high accuracy and, therefore, can be used as an assistant to help professionals detect COVID-19 patients accurately.

Severity of COVID-19 patients with coexistence of asthma and vitamin D deficiency.

Coronavirus disease 2019 (COVID-19)-driven global pandemic triggered innumerable health complications, imposing great challenges in managing other respiratory diseases like asthma. Furthermore, increases in the underlying inflammation involved in the fatality of COVID-19 have been linked with lack of vitamin D. In this research work, we intend to investigate the possible genetic linkage of asthma and vitamin D deficiency with the severity and fatality of COVID-19 using a network-based approach. We identified and analysed 41 and 14 differentially expressed genes (DEGs) of COVID-19 being common with asthma and vitamin D deficiency, respectively, through the comparative differential gene expression analysis and their footprints on signalling pathways. Gene set enrichment analysis for GO terms and signalling pathways reveals key biological activities, including inflammatory response-related pathways (e.g., cytokine- and chemokine-mediated signalling pathways, IL-17, and TNF signalling pathways). Besides, the Protein-Protein Interaction network analysis of those DEGs reveals hub proteins, some of which are reported as inflammatory antiviral interferon-stimulated biomarkers that potentially drive the cytokine storm leading to COVID-19 severity and fatality, and contributes in the early stage of viral replication, respectively. Moreover, the regulatory network analysis found these DEGs associated with antiviral and tumour inhibitory transcription factors and micro-RNAs. Finally, drug-target enrichment analysis yields tetradioxin, estradiol, arsenenous acid, and zinc, which have been reported to be effective in suppressing the pro-inflammatory cytokines production, and other respiratory tract infections. Our results yield shared biomarker-driven key hypotheses followed by network-based analytics, demystifying the mechanistic details of COVID-19 comorbidity of asthma and vitamin D deficiency with their potential therapeutic implications.

Systems biology models to identify the influence of SARS-CoV-2 infections to the progression of human autoimmune diseases.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been circulating since 2019, and its global dominance is rising. Evidences suggest the respiratory illness SARS-CoV-2 has a sensitive affect on causing organ damage and other complications to the patients with autoimmune diseases (AD), posing a significant risk factor. The genetic interrelationships and molecular appearances between SARS-CoV-2 and AD are yet unknown. We carried out the transcriptomic analytical framework to delve into the SARS-CoV-2 impacts on AD progression. We analyzed both gene expression microarray and RNA-Seq datasets from SARS-CoV-2 and AD affected tissues. With neighborhood-based benchmarks and multilevel network topology, we obtained dysfunctional signaling and ontological pathways, gene disease (diseasesome) association network and protein-protein interaction network (PPIN), uncovered essential shared infection recurrence connectivities with biological insights underlying between SARS-CoV-2 and AD. We found a total of 77, 21, 9, 54 common DEGs for SARS-CoV-2 and inflammatory bowel disorder (IBD), SARS-CoV-2 and rheumatoid arthritis (RA), SARS-CoV-2 and systemic lupus erythematosus (SLE) and SARS-CoV-2 and type 1 diabetes (T1D). The enclosure of these common DEGs with bimolecular networks revealed 10 hub proteins (FYN, VEGFA, CTNNB1, KDR, STAT1, B2M, CD3G, ITGAV, TGFB3). Drugs such as amlodipine besylate, vorinostat, methylprednisolone, and disulfiram have been identified as a common ground between SARS-CoV-2 and AD from drug repurposing investigation which will stimulate the optimal selection of medications in the battle against this ongoing pandemic triggered by COVID-19.

MLBioIGE: integration and interplay of machine learning and bioinformatics approach to identify the genetic effect of SARS-COV-2 on idiopathic pulmonary fibrosis patients.

SARS-CoV-2, the virus that causes COVID-19, is a current concern for people worldwide. The virus has recently spread worldwide and is out of control in several countries, putting the outbreak into a terrifying phase. Machine learning with transcriptome analysis has advanced in recent years. Its outstanding performance in several fields has emerged as a potential option to find out how SARS-CoV-2 is related to other diseases. Idiopathic pulmonary fibrosis (IPF) disease is caused by long-term lung injury, a risk factor for SARS-CoV-2. In this article, we used a variety of combinatorial statistical approaches, machine learning, and bioinformatics tools to investigate how the SARS-CoV-2 affects IPF patients' complexity. For this study, we employed two RNA-seq datasets. The unique contributions include common genes identification to identify shared pathways and drug targets, PPI network to identify hub-genes and basic modules, and the interaction of transcription factors (TFs) genes and TFs-miRNAs with common differentially expressed genes also placed on the datasets. Furthermore, we used gene ontology and molecular pathway analysis to do functional analysis and discovered that IPF patients have certain standard connections with the SARS-CoV-2 virus. A detailed investigation was carried out to recommend therapeutic compounds for IPF patients affected by the SARS-CoV-2 virus.

Discovering Common Pathophysiological Processes between COVID-19 and Cystic Fibrosis by Differential Gene Expression Pattern Analysis.

Coronaviruses are a family of viruses that infect mammals and birds. Coronaviruses cause infections of the respiratory system in humans, which can be minor or fatal. A comparative transcriptomic analysis has been performed to establish essential profiles of the gene expression of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) linked to cystic fibrosis (CF). Transcriptomic studies have been carried out in relation to SARS-CoV-2 since a number of people have been diagnosed with CF. The recognition of differentially expressed genes demonstrated 8 concordant genes shared between the SARS-CoV-2 and CF. Extensive gene ontology analysis and the discovery of pathway enrichment demonstrated SARS-CoV-2 response to CF. The gene ontological terms and pathway enrichment mechanisms derived from this research may affect the production of successful drugs, especially for the people with the following disorder. Identification of TF-miRNA association network reveals the interconnection between TF genes and miRNAs, which may be effective to reveal the other influenced disease that occurs for SARS-CoV-2 to CF. The enrichment of pathways reveals SARS-CoV-2-associated CF mostly engaged with the type of innate immune system, Toll-like receptor signaling pathway, pantothenate and CoA biosynthesis, allograft rejection, graft-versus-host disease, intestinal immune network for IgA production, mineral absorption, autoimmune thyroid disease, legionellosis, viral myocarditis, inflammatory bowel disease (IBD), etc. The drug compound identification demonstrates that the drug targets of IMIQUIMOD and raloxifene are the most significant with the significant hub DEGs.

Systems Biology and Bioinformatics approach to Identify blood based signatures molecules and drug targets of patient with COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection results in the development of a highly contagious respiratory ailment known as new coronavirus disease (COVID-19). Despite the fact that the prevalence of COVID-19 continues to rise, it is still unclear how people become infected with SARS-CoV-2 and how patients with COVID-19 become so unwell. Detecting biomarkers for COVID-19 using peripheral blood mononuclear cells (PBMCs) may aid in drug development and treatment. This research aimed to find blood cell transcripts that represent levels of gene expression associated with COVID-19 progression. Through the development of a bioinformatics pipeline, two RNA-Seq transcriptomic datasets and one microarray dataset were studied and discovered 102 significant differentially expressed genes (DEGs) that were shared by three datasets derived from PBMCs. To identify the roles of these DEGs, we discovered disease-gene association networks and signaling pathways, as well as we performed gene ontology (GO) studies and identified hub protein. Identified significant gene ontology and molecular pathways improved our understanding of the pathophysiology of COVID-19, and our identified blood-based hub proteins TPX2, DLGAP5, NCAPG, CCNB1, KIF11, HJURP, AURKB, BUB1B, TTK, and TOP2A could be used for the development of therapeutic intervention. In COVID-19 subjects, we discovered effective putative connections between pathological processes in the transcripts blood cells, suggesting that blood cells could be used to diagnose and monitor the disease's initiation and progression as well as developing drug therapeutics.

A deep learning approach using effective preprocessing techniques to detect COVID-19 from chest CT-scan and X-ray images.

Coronavirus disease-19 (COVID-19) is a severe respiratory viral disease first reported in late 2019 that has spread worldwide. Although some wealthy countries have made significant progress in detecting and containing this disease, most underdeveloped countries are still struggling to identify COVID-19 cases in large populations. With the rising number of COVID-19 cases, there are often insufficient COVID-19 diagnostic kits and related resources in such countries. However, other basic diagnostic resources often do exist, which motivated us to develop Deep Learning models to assist clinicians and radiologists to provide prompt diagnostic support to the patients. In this study, we have developed a deep learning-based COVID-19 case detection model trained with a dataset consisting of chest CT scans and X-ray images. A modified ResNet50V2 architecture was employed as deep learning architecture in the proposed model. The dataset utilized to train the model was collected from various publicly available sources and included four class labels: confirmed COVID-19, normal controls and confirmed viral and bacterial pneumonia cases. The aggregated dataset was preprocessed through a sharpening filter before feeding the dataset into the proposed model. This model attained an accuracy of 96.452% for four-class cases (COVID-19/Normal/Bacterial pneumonia/Viral pneumonia), 97.242% for three-class cases (COVID-19/Normal/Bacterial pneumonia) and 98.954% for two-class cases (COVID-19/Viral pneumonia) using chest X-ray images. The model acquired a comprehensive accuracy of 99.012% for three-class cases (COVID-19/Normal/Community-acquired pneumonia) and 99.99% for two-class cases (Normal/COVID-19) using CT-scan images of the chest. This high accuracy presents a new and potentially important resource to enable radiologists to identify and rapidly diagnose COVID-19 cases with only basic but widely available equipment.

Effects of Bacille Calmette Guerin (BCG) vaccination during COVID-19 infection.

The coronavirus disease 2019 (COVID-19) is caused by the infection of highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as the novel coronavirus. In most countries, the containment of this virus spread is not controlled, which is driving the pandemic towards a more difficult phase. In this study, we investigated the impact of the Bacille Calmette Guerin (BCG) vaccination on the severity and mortality of COVID-19 by performing transcriptomic analyses of SARS-CoV-2 infected and BCG vaccinated samples in peripheral blood mononuclear cells (PBMC). A set of common differentially expressed genes (DEGs) were identified and seeded into their functional enrichment analyses via Gene Ontology (GO)-based functional terms and pre-annotated molecular pathways databases, and their Protein-Protein Interaction (PPI) network analysis. We further analysed the regulatory elements, possible comorbidities and putative drug candidates for COVID-19 patients who have not been BCG-vaccinated. Differential expression analyses of both BCG-vaccinated and COVID-19 infected samples identified 62 shared DEGs indicating their discordant expression pattern in their respected conditions compared to control. Next, PPI analysis of those DEGs revealed 10 hub genes, namely ITGB2, CXCL8, CXCL1, CCR2, IFNG, CCL4, PTGS2, ADORA3, TLR5 and CD33. Functional enrichment analyses found significantly enriched pathways/GO terms including cytokine activities, lysosome, IL-17 signalling pathway, TNF-signalling pathways. Moreover, a set of identified TFs, miRNAs and potential drug molecules were further investigated to assess their biological involvements in COVID-19 and their therapeutic possibilities. Findings showed significant genetic interactions between BCG vaccination and SARS-CoV-2 infection, suggesting an interesting prospect of the BCG vaccine in relation to the COVID-19 pandemic. We hope it may potentially trigger further research on this critical phenomenon to combat COVID-19 spread.

Bioinformatics and system biology approaches to identify pathophysiological impact of COVID-19 to the progression and severity of neurological diseases.

The Coronavirus Disease 2019 (COVID-19) still tends to propagate and increase the occurrence of COVID-19 across the globe. The clinical and epidemiological analyses indicate the link between COVID-19 and Neurological Diseases (NDs) that drive the progression and severity of NDs. Elucidating why some patients with COVID-19 influence the progression of NDs and patients with NDs who are diagnosed with COVID-19 are becoming increasingly sick, although others are not is unclear. In this research, we investigated how COVID-19 and ND interact and the impact of COVID-19 on the severity of NDs by performing transcriptomic analyses of COVID-19 and NDs samples by developing the pipeline of bioinformatics and network-based approaches. The transcriptomic study identified the contributing genes which are then filtered with cell signaling pathway, gene ontology, protein-protein interactions, transcription factor, and microRNA analysis. Identifying hub-proteins using protein-protein interactions leads to the identification of a therapeutic strategy. Additionally, the incorporation of comorbidity interactions score enhances the identification beyond simply detecting novel biological mechanisms involved in the pathophysiology of COVID-19 and its NDs comorbidities. By computing the semantic similarity between COVID-19 and each of the ND, we have found gene-based maximum semantic score between COVID-19 and Parkinson's disease, the minimum semantic score between COVID-19 and Multiple sclerosis. Similarly, we have found gene ontology-based maximum semantic score between COVID-19 and Huntington disease, minimum semantic score between COVID-19 and Epilepsy disease. Finally, we validated our findings using gold-standard databases and literature searches to determine which genes and pathways had previously been associated with COVID-19 and NDs.

COVID-19 Pandemic Outbreak in the Subcontinent: A Data Driven Analysis.

Human civilization is experiencing a critical situation that presents itself for a new coronavirus disease 2019 (COVID-19). This virus emerged in late December 2019 in Wuhan city, Hubei, China. The grim fact of COVID-19 is, it is highly contagious in nature, therefore, spreads rapidly all over the world and causes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Responding to the severity of COVID-19 research community directs the attention to the analysis of COVID-19, to diminish its antagonistic impact towards society. Numerous studies claim that the subcontinent, i.e., Bangladesh, India, and Pakistan, could remain in the worst affected region by the COVID-19. In order to prevent the spread of COVID-19, it is important to predict the trend of COVID-19 beforehand the planning of effective control strategies. Fundamentally, the idea is to dependably estimate the reproduction number to judge the spread rate of COVID-19 in a particular region. Consequently, this paper uses publicly available epidemiological data of Bangladesh, India, and Pakistan to estimate the reproduction numbers. More specifically, we use various models (for example, susceptible infection recovery (SIR), exponential growth (EG), sequential Bayesian (SB), maximum likelihood (ML) and time dependent (TD)) to estimate the reproduction numbers and observe the model fitness in the corresponding data set. Experimental results show that the reproduction numbers produced by these models are greater than 1.2 (approximately) indicates that COVID-19 is gradually spreading in the subcontinent.

COVID-19 identification from volumetric chest CT scans using a progressively resized 3D-CNN incorporating segmentation, augmentation, and class-rebalancing.

The novel COVID-19 is a global pandemic disease overgrowing worldwide. Computer-aided screening tools with greater sensitivity are imperative for disease diagnosis and prognosis as early as possible. It also can be a helpful tool in triage for testing and clinical supervision of COVID-19 patients. However, designing such an automated tool from non-invasive radiographic images is challenging as many manually annotated datasets are not publicly available yet, which is the essential core requirement of supervised learning schemes. This article proposes a 3D Convolutional Neural Network (CNN)-based classification approach considering both the inter-and intra-slice spatial voxel information. The proposed system is trained end-to-end on the 3D patches from the whole volumetric Computed Tomography (CT) images to enlarge the number of training samples, performing the ablation studies on patch size determination. We integrate progressive resizing, segmentation, augmentations, and class-rebalancing into our 3D network. The segmentation is a critical prerequisite step for COVID-19 diagnosis enabling the classifier to learn prominent lung features while excluding the outer lung regions of the CT scans. We evaluate all the extensive experiments on a publicly available dataset named MosMed, having binary- and multi-class chest CT image partitions. Our experimental results are very encouraging, yielding areas under the Receiver Operating Characteristics (ROC) curve of 0 . 914 ± 0 . 049 and 0 . 893 ± 0 . 035 for the binary- and multi-class tasks, respectively, applying 5-fold cross-validations. Our method's promising results delegate it as a favorable aiding tool for clinical practitioners and radiologists to assess COVID-19.

Identification of biomarkers and pathways for the SARS-CoV-2 infections that make complexities in pulmonary arterial hypertension patients.

This study aimed to identify significant gene expression profiles of the human lung epithelial cells caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We performed a comparative genomic analysis to show genomic observations between SARS-CoV and SARS-CoV-2. A phylogenetic tree has been carried for genomic analysis that confirmed the genomic variance between SARS-CoV and SARS-CoV-2. Transcriptomic analyses have been performed for SARS-CoV-2 infection responses and pulmonary arterial hypertension (PAH) patients' lungs as a number of patients have been identified who faced PAH after being diagnosed with coronavirus disease 2019 (COVID-19). Gene expression profiling showed significant expression levels for SARS-CoV-2 infection responses to human lung epithelial cells and PAH lungs as well. Differentially expressed genes identification and integration showed concordant genes (SAA2, S100A9, S100A8, SAA1, S100A12 and EDN1) for both SARS-CoV-2 and PAH samples, including S100A9 and S100A8 genes that showed significant interaction in the protein-protein interactions network. Extensive analyses of gene ontology and signaling pathways identification provided evidence of inflammatory responses regarding SARS-CoV-2 infections. The altered signaling and ontology pathways that have emerged from this research may influence the development of effective drugs, especially for the people with preexisting conditions. Identification of regulatory biomolecules revealed the presence of active promoter gene of SARS-CoV-2 in Transferrin-micro Ribonucleic acid (TF-miRNA) co-regulatory network. Predictive drug analyses provided concordant drug compounds that are associated with SARS-CoV-2 infection responses and PAH lung samples, and these compounds showed significant immune response against the RNA viruses like SARS-CoV-2, which is beneficial in therapeutic development in the COVID-19 pandemic.

Diseasome and comorbidities complexities of SARS-CoV-2 infection with common malignant diseases.

With the increasing number of immunoinflammatory complexities, cancer patients have a higher risk of serious disease outcomes and mortality with SARS-CoV-2 infection which is still not clear. In this study, we aimed to identify infectome, diseasome and comorbidities between COVID-19 and cancer via comprehensive bioinformatics analysis to identify the synergistic severity of the cancer patient for SARS-CoV-2 infection. We utilized transcriptomic datasets of SARS-CoV-2 and different cancers from Gene Expression Omnibus and Array Express Database to develop a bioinformatics pipeline and software tools to analyze a large set of transcriptomic data and identify the pathobiological relationships between the disease conditions. Our bioinformatics approach revealed commonly dysregulated genes (MARCO, VCAN, ACTB, LGALS1, HMOX1, TIMP1, OAS2, GAPDH, MSH3, FN1, NPC2, JUND, CHI3L1, GPNMB, SYTL2, CASP1, S100A8, MYO10, IGFBP3, APCDD1, COL6A3, FABP5, PRDX3, CLEC1B, DDIT4, CXCL10 and CXCL8), common gene ontology (GO), molecular pathways between SARS-CoV-2 infections and cancers. This work also shows the synergistic complexities of SARS-CoV-2 infections for cancer patients through the gene set enrichment and semantic similarity. These results highlighted the immune systems, cell activation and cytokine production GO pathways that were observed in SARS-CoV-2 infections as well as breast, lungs, colon, kidney and thyroid cancers. This work also revealed ribosome biogenesis, wnt signaling pathway, ribosome, chemokine and cytokine pathways that are commonly deregulated in cancers and COVID-19. Thus, our bioinformatics approach and tools revealed interconnections in terms of significant genes, GO, pathways between SARS-CoV-2 infections and malignant tumors.

Designing a multi-epitope vaccine candidate to combat MERS-CoV by employing an immunoinformatics approach.

Currently, no approved vaccine is available against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes severe respiratory disease. The spike glycoprotein is typically considered a suitable target for MERS-CoV vaccine candidates. A computational strategy can be used to design an antigenic vaccine against a pathogen. Therefore, we used immunoinformatics and computational approaches to design a multi-epitope vaccine that targets the spike glycoprotein of MERS-CoV. After using numerous immunoinformatics tools and applying several immune filters, a poly-epitope vaccine was constructed comprising cytotoxic T-cell lymphocyte (CTL)-, helper T-cell lymphocyte (HTL)-, and interferon-gamma (IFN-γ)-inducing epitopes. In addition, various physicochemical, allergenic, and antigenic profiles were evaluated to confirm the immunogenicity and safety of the vaccine. Molecular interactions, binding affinities, and the thermodynamic stability of the vaccine were examined through molecular docking and dynamic simulation approaches, during which we identified a stable and strong interaction with Toll-like receptors (TLRs). In silico immune simulations were performed to assess the immune-response triggering capabilities of the vaccine. This computational analysis suggested that the proposed vaccine candidate would be structurally stable and capable of generating an effective immune response to combat viral infections; however, experimental evaluations remain necessary to verify the exact safety and immunogenicity profile of this vaccine.