INFLUENCE OF DEATH ANXIETY ON THE PREVENTIVE PRACTICES OF HEALTHCARE PROFESSIONALS DURING COVID-19 OUTBREAK

OBJECTIVES: To ascertain the degree of death anxiety in healthcare professionals and their preventive practices during the ongoing pandemic and to find correlations between these two variables. METHODS: This cross-sectional study was conducted on healthcare professionals working in Combined Military Hospital, Lahore, Pakistan, from July 2020 to February 2021. A descriptive online questionnaire was distributed to measure demography, death anxiety using Collette-Lester Fear of Death Scale Revised and preventive practices using the prevention section of WHO European Region COVID-19 survey tool and guidance. Data were analyzed using SPSS version 24. RESULTS: Out of 136 subjects, 65 (47.8%) were male and 71 (52.2%) were female. Median (IQR) age of the participants was 28 (26-40) years. Median total degree of death anxiety was 83 (66-107). The four subscales showed Median (IQR) scores as follows: your own death 18 (12-27), your own dying 20 (15-27), the death of others 23 (18-28), and the dying of others 22 (16-29). Death anxiety was mild in 55 (40.4%), moderate in 65 (47.8%) and high in 16 (11.8%) participants. Significant association of female gender (p=0.002), experience of death of a patient (p=0.001) or loved one (p=0.001) was found with death anxiety. Zero participants recorded a high preventive practice score. CONCLUSION: A significant proportion of healthcare professionals suffered from undiagnosed moderate levels of death anxiety. The level of preventive practices amongst healthcare professionals was moderate to low. Death anxiety had no correlation with preventive practices. Further study is required to investigate the reason behind these unconventional findings. © 2022, Khyber Medical University. All rights reserved.

A Novel Fusion Model of Hand-Crafted Features with Deep Convolutional Neural Networks for Classification of Several Chest Diseases using X-ray Images

With the continuing global pandemic of coronavirus (COVID-19) sickness, it is critical to seek diagnostic approaches that are both effective and rapid to limit the number of people infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The results of recent research suggest that radiological images include important information related to COVID-19 and other chest diseases. As a result, the use of deep learning (DL) to assist in the automated diagnosis of chest diseases may prove useful as a diagnostic tool in the future. In this study, we propose a novel fusion model of hand-crafted features with deep convolutional neural networks (DCNNs) for classifying ten different chest diseases such as COVID-19, lung cancer (LC), atelectasis (ATE), consolidation lung (COL), tuberculosis (TB), pneumothorax (PNET), edema (EDE), pneumonia (PNEU), pleural thickening (PLT), and normal using chest X-rays (CXR). The method that has been suggested is split down into three distinct parts. The first step involves utilizing the Info-MGAN network to perform segmentation on the raw CXR data to construct lung images of ten different chest diseases. In the second step, the segmented lung images are fed into a novel pipeline that extracts discriminatory features by using hand-crafted techniques such as SURF and ORB, and then these extracted features are fused to the trained DCNNs. At last, various machine learning (ML) models have been used as the last layer of the DCNN models for the classification of chest diseases. Comparison is made between the performance of various proposed architectures for classification, all of which integrate DCNNs, key point extraction methods, and ML models. We were able to attain a classification accuracy of 98.20% for testing by utilizing the VGG-19 model with a softmax layer in conjunction with the ORB technique. Screening for COVID-19 and other lung ailments can be accomplished using the method that has been proposed. The robustness of the model was further confirmed by statistical analyses of the datasets using McNemar’s and ANOVA tests respectively. Author

Effect of Lockdown on the Air Quality of Four Major Cities in Pakistan During the COVID-19 Pandemic

This study attempted to evaluate the effect of lockdown on the air quality of four major cities in Pakistan: Karachi, Lahore, Islamabad, and Peshawar. Particulate matter (PM2.5) concentration and U.S. Environmental Protection Agency Air Quality Index (AQI) were used to determine air quality before and after lockdown. We found that air quality in all the cities improved after lockdown was imposed: PM2.5 concentrations in Karachi and Lahore decreased by 62% and in Peshawar and Islamabad by 57% and 55%, respectively. AQI in Karachi and Islamabad improved from Unhealthy to Moderate and in Peshawar and Lahore from Unhealthy to Unhealthy for Sensitive Groups. Formal complete lockdown in Pakistan was imposed on March 24, 2020, and lasted until May 10, 2020, after which partial or smart lockdown was still in place. Maximum improvement in air quality was observed in April 2020, with concentrations starting to increase in May 2020 following the ease of restrictions. © 2023, National Environmental Health Association. All rights reserved.

Coronavirus infection outbreak: comparison with other viral infection outbreak

This chapter provides a comparison of the current novel coronavirus disease 2019 (COVID-19) with past pandemics: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and pandemic influenza viruses in terms of transmissibility, hospitalization, and mortality rates. © 2022 Elsevier Inc. All rights reserved.

ORFeome Phage Display Reveals a Major Immunogenic Epitope on the S2 Subdomain of SARS-CoV-2 Spike Protein.

The development of antibody therapies against SARS-CoV-2 remains a challenging task during the ongoing COVID-19 pandemic. All approved therapeutic antibodies are directed against the receptor binding domain (RBD) of the spike, and therefore lose neutralization efficacy against emerging SARS-CoV-2 variants, which frequently mutate in the RBD region. Previously, phage display has been used to identify epitopes of antibody responses against several diseases. Such epitopes have been applied to design vaccines or neutralize antibodies. Here, we constructed an ORFeome phage display library for the SARS-CoV-2 genome. Open reading frames (ORFs) representing the SARS-CoV-2 genome were displayed on the surface of phage particles in order to identify enriched immunogenic epitopes from COVID-19 patients. Library quality was assessed by both NGS and epitope mapping of a monoclonal antibody with a known binding site. The most prominent epitope captured represented parts of the fusion peptide (FP) of the spike. It is associated with the cell entry mechanism of SARS-CoV-2 into the host cell; the serine protease TMPRSS2 cleaves the spike within this sequence. Blocking this mechanism could be a potential target for non-RBD binding therapeutic anti-SARS-CoV-2 antibodies. As mutations within the FP amino acid sequence have been rather rare among SARS-CoV-2 variants so far, this may provide an advantage in the fight against future virus variants.

ORFeome Phage Display Reveals a Major Immunogenic Epitope on the S2 Subdomain of SARS-CoV-2 Spike Protein

The development of antibody therapies against SARS-CoV-2 remains a challenging task during the ongoing COVID-19 pandemic. All approved therapeutic antibodies are directed against the receptor binding domain (RBD) of the spike, and therefore lose neutralization efficacy against emerging SARS-CoV-2 variants, which frequently mutate in the RBD region. Previously, phage display has been used to identify epitopes of antibody responses against several diseases. Such epitopes have been applied to design vaccines or neutralize antibodies. Here, we constructed an ORFeome phage display library for the SARS-CoV-2 genome. Open reading frames (ORFs) representing the SARS-CoV-2 genome were displayed on the surface of phage particles in order to identify enriched immunogenic epitopes from COVID-19 patients. Library quality was assessed by both NGS and epitope mapping of a monoclonal antibody with a known binding site. The most prominent epitope captured represented parts of the fusion peptide (FP) of the spike. It is associated with the cell entry mechanism of SARS-CoV-2 into the host cell;the serine protease TMPRSS2 cleaves the spike within this sequence. Blocking this mechanism could be a potential target for non-RBD binding therapeutic anti-SARS-CoV-2 antibodies. As mutations within the FP amino acid sequence have been rather rare among SARS-CoV-2 variants so far, this may provide an advantage in the fight against future virus variants.

Variations in orthopaedic trauma presentation during COVID-19 lockdown

Introduction: In living memory there has never been a start to the year as 2020, due to Covid -19 Pandemic. Like every other surgical speciality, Orthopaedic trauma surgery faced significant challenges during this period in terms of numbers as well as variation in trauma patients' presentation. Aim: The purpose of our study is to analyse the numbers and variations in orthopaedic trauma and its presentations during the pandemic in comparison with 2018 and 2019. Methods: The data for this audit was collected from orthopaedic register of Our lady of Lourdes Hospital, Ireland. Patients operated under orthopaedic trauma team in three months period (March, April & May) in 2018, 2019 and 2020 were selected for analysis and comparison. Results: In 2020, total number of surgeries were 32% less than the average of previous 2 years. (373 in 2020 vs 543 in 2019 and 551 in 2018). Similarly, the paediatric trauma surgeries dropped by 32 % in this period. Significantly lower proportion of sport related injuries, RTAs, and assaults presented in 2020. Higher proportion of trauma resulting from simple slip, falls from height and trampoline was observed in this period compared to previous two years. Slightly higher proportion of tibial pilon, calcaneum and peri-prosthetic fractures was noted as compared to previous years. Conclusions: Significant reduction in total number of trauma cases as well as high energy trauma (Road Traffic Accidents, Sports Trauma) was observed due to limited mobility in pandemic, whereas higher proportion of low energy fractures occurred during this period of restrictions.

Rapid SARS-CoV-2 Adaptation to Available Cellular Proteases.

Recent emergence of SARS-CoV-1 variants demonstrates the potential of this virus for targeted evolution, despite its overall genomic stability. Here we show the dynamics and the mechanisms behind the rapid adaptation of SARS-CoV-2 to growth in Vero E6 cells. The selective advantage for growth in Vero E6 cells is due to increased cleavage efficiency by cathepsins at the mutated S1/S2 site. S1/S2 site also constitutes a heparan sulfate (HS) binding motif that influenced virus growth in Vero E6 cells, but HS antagonist did not inhibit virus adaptation in these cells. The entry of Vero E6-adapted virus into human cells is defective because the mutated spike variants are poorly processed by furin or TMPRSS2. Minor subpopulation that lack the furin cleavage motif in the spike protein rapidly become dominant upon passaging through Vero E6 cells, but wild type sequences are maintained at low percentage in the virus swarm and mediate a rapid reverse adaptation if the virus is passaged again on TMPRSS2+ human cells. Our data show that the spike protein of SARS-CoV-2 can rapidly adapt itself to available proteases and argue for deep sequence surveillance to identify the emergence of novel variants. IMPORTANCE Recently emerging SARS-CoV-2 variants B.1.1.7 (alpha variant), B.1.617.2 (delta variant), and B.1.1.529 (omicron variant) harbor spike mutations and have been linked to increased virus pathogenesis. The emergence of these novel variants highlights coronavirus adaptation and evolution potential, despite the stable consensus genotype of clinical isolates. We show that subdominant variants maintained in the virus population enable the virus to rapidly adapt to selection pressure. Although these adaptations lead to genotype change, the change is not absolute and genomes with original genotype are maintained in the virus swarm. Thus, our results imply that the relative stability of SARS-CoV-2 in numerous independent clinical isolates belies its potential for rapid adaptation to new conditions.

Two-step Feature Selection for Predicting Mortality Risk in COVID-19 Patients

COVID-19 pandemic is causing serious impact on our society. The whole world is suffering from financial, social, psychological, and other health crisis. One of the various challenges faced is the lack of health and medical facilities around the globe. It is very crucial to properly manage the available resources to save the lives of COVID-19 affected patients. This study proposes an intelligent model to facilitate the hospitals and medical facilities to diagnose which patients are in serious conditions and needs priority health services. The proposed model is based on feature selection-based mechanism, where most dominating features are identified to best discriminate among the serious patients and the less affected patients. We adopted two-step strategy, where filter measure is applied to rank the features according to their relevance in the first step, and Genetic Algorithm is applied with Decision Tree classifier to find the best feature subset in the second step. The results are reported in terms of classification accuracy and the most dominating features are also identified to help the medical practitioners. © 2021 IEEE.

MCMV-based vaccine vectors expressing full-length viral proteins provide long-term humoral immune protection upon a single-shot vaccination.

Global pandemics caused by influenza or coronaviruses cause severe disruptions to public health and lead to high morbidity and mortality. There remains a medical need for vaccines against these pathogens. CMV (cytomegalovirus) is a ß-herpesvirus that induces uniquely robust immune responses in which remarkably large populations of antigen-specific CD8+ T cells are maintained for a lifetime. Hence, CMV has been proposed and investigated as a novel vaccine vector for expressing antigenic peptides or proteins to elicit protective cellular immune responses against numerous pathogens. We generated two recombinant murine CMV (MCMV) vaccine vectors expressing hemagglutinin (HA) of influenza A virus (MCMVHA) or the spike protein of severe acute respiratory syndrome coronavirus 2 (MCMVS). A single injection of MCMVs expressing either viral protein induced potent neutralizing antibody responses, which strengthened over time. Importantly, MCMVHA-vaccinated mice were protected from illness following challenge with the influenza virus, and we excluded that this protection was due to the effects of memory T cells. Conclusively, we show here that MCMV vectors induce not only long-term cellular immunity but also humoral responses that provide long-term immune protection against clinically relevant respiratory pathogens.

Variations in orthopedic trauma presentation during COVID-19 lockdown

Introduction: The first national lockdown was imposed in Ireland from 27th March 2020, to combat the spread of Coronavirus. All nonessential travel, businesses, sporting activities and schools were closed. The elderly were advised to cocoon. The roadmap to easing the restrictions started in May. The lockdown measures resulted in people spending more time indoors, with impact on social and personal wellbeing This had the potential to increase alcohol consumption, self inflicted injuries and neglect. The purpose of our study is to analyze the variations in orthopedic trauma presentations during the pandemic compared to similar period in 2018 and 2019 Method: Retrospective data was collected from Orthopedic theatre registry of Our Lady of Lourdes Hospital, Drogheda, Co Louth, Ireland Patients operated by orthopedic trauma team in three months period (March, April & May) in 2018, 2019 and 2020 were selected for analysis and comparison Result: Total number of surgeries performed in March-May 2018, 2019 and 2020 were 551, 505 and 373 showing a significant reduction in 2020 as compared to previous years. Trauma surgeries performed on children in March-May 2018,2019 and 2020 were 132,131 and 90 respectively showing a similar downward trend. Surgeries were further categorized into Major +, Major, Intermediate and Minor according to their level of complexity. Although there was a significant reduction seen in Major, Intermediate and Minor surgeries, no significant difference was observed in Major + surgeries (73 in March-May 2020 vs. 79 in March-May 2019 and 57 in March-May 2018) Conclusion: Significant reduction was seen in overall trauma surgeries which is attributable to lockdown measures. The difference in trend between Major + and other categories of surgeries can be explained by the reduction in sporting injuries and injuries in children whereas no significant difference was noted in hip fractures .

A SARS-CoV-2 neutralizing antibody selected from COVID-19 patients binds to the ACE2-RBD interface and is tolerant to most known RBD mutations.

The novel betacoronavirus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) causes a form of severe pneumonia disease called coronavirus disease 2019 (COVID-19). To develop human neutralizing anti-SARS-CoV-2 antibodies, antibody gene libraries from convalescent COVID-19 patients were constructed and recombinant antibody fragments (scFv) against the receptor-binding domain (RBD) of the spike protein were selected by phage display. The antibody STE90-C11 shows a subnanometer IC50 in a plaque-based live SARS-CoV-2 neutralization assay. The in vivo efficacy of the antibody is demonstrated in the Syrian hamster and in the human angiotensin-converting enzyme 2 (hACE2) mice model. The crystal structure of STE90-C11 Fab in complex with SARS-CoV-2-RBD is solved at 2.0 Å resolution showing that the antibody binds at the same region as ACE2 to RBD. The binding and inhibition of STE90-C11 is not blocked by many known emerging RBD mutations. STE90-C11-derived human IgG1 with FcγR-silenced Fc (COR-101) is undergoing Phase Ib/II clinical trials for the treatment of moderate to severe COVID-19.