Inequalities in access to NHS primary care dental services in Scotland during the COVID-19 pandemic.

Introduction This study aimed to quantify the impact of the COVID-19 pandemic on access and inequalities in primary care dental services among children and adults in Scotland.Methods Access was measured as any NHS Scotland primary care dental contacts derived from administrative data from January 2019 to May 2022, linked to the area-based Scottish Index of Multiple Deprivation for children and adults, and related to population denominator estimates from National Record Scotland. Inequalities for pre-pandemic (January 2019-January 2020) and recent (December 2021-February 2022, and March 2022-May 2022) periods for both children and adults were calculated and compared using the slope index of inequality and relative index of inequality.Results Following the first lockdown (March 2020) there was a dramatic fall to near zero dental contacts, followed by a slow recovery to 64.8% of pre-pandemic levels by May 2022. There was initial widening of relative inequalities in dental contacts in early 2022, which, more recently, had begun to return to pre-pandemic levels.Conclusion COVID-19 had a major impact on access to NHS primary dental care, and while inequalities in access are apparent as services recover from lockdown, these inequalities are not a new phenomenon.

1,4,9,9-tetramethyloctahydro-4,7-(epoxymethano)azulen-5(1H)-one, a natural product as a potential inhibitor of COVID-19: Extraction, crystal structure, and virtual screening approach

In the present work, we describe the extraction of a natural product namely 1,4,9,9-tetramethyloctahydro-4,7-(epoxymethano)azulen-5(1H)-one, and its structure was confirmed by single crystal X-ray diffraction analysis. The conformations of the 5-, 6-, and 7-membered rings in the title compound, C15H24O2, have been probed by a Cremer-Pople puckering analysis. C—H···O hydrogen bonds generate chains in the crystal that stretch along the c-axis direction. The Hirshfeld surface analysis method was used to stabilize the crystal packing of the natural compound. Accompanied by experimental studies, quantum chemical calculations were also performed to compare the structural elucidation and the results of these geometrical parameters exhibited excellent agreement. The compound was also docked with several drug targets of the SARS-CoV-2 virus and found to show the best binding with the main protease enzyme, having a binding energy of -12.31 kcal/mol and interacting with His41 and Cys145 residues. The dynamic stability deciphered the complex to be stable with an average RMSD of 3.8 Å. The compound dynamics with the enzyme showed the compound conformation to be highly stable. The intermolecular binding free energy determined the compound-main protease enzyme to show high interaction energy of < 40 kcal/mol. Together, these studies demonstrate the compound to be a lead structure against SARS-CoV-2.

1,4,9,9-tetramethyloctahydro-4,7-(epoxymethano)azulen-5(1H)-one, a natural product as a potential inhibitor of COVID-19: Extraction, crystal structure, and virtual screening approach.

In the present work, we describe the extraction of a natural product namely 1,4,9,9-tetramethyloctahydro-4,7-(epoxymethano)azulen-5(1H)-one, and its structure was confirmed by single crystal X-ray diffraction analysis. The conformations of the 5-, 6-, and 7-membered rings in the title compound, C15H24O2, have been probed by a Cremer-Pople puckering analysis. C-H···O hydrogen bonds generate chains in the crystal that stretch along the c-axis direction. The Hirshfeld surface analysis method was used to stabilize the crystal packing of the natural compound. Accompanied by experimental studies, quantum chemical calculations were also performed to compare the structural elucidation and the results of these geometrical parameters exhibited excellent agreement. The compound was also docked with several drug targets of the SARS-CoV-2 virus and found to show the best binding with the main protease enzyme, having a binding energy of -12.31 kcal/mol and interacting with His41 and Cys145 residues. The dynamic stability deciphered the complex to be stable with an average RMSD of 3.8 Å. The compound dynamics with the enzyme showed the compound conformation to be highly stable. The intermolecular binding free energy determined the compound-main protease enzyme to show high interaction energy of < 40 kcal/mol. Together, these studies demonstrate the compound to be a lead structure against SARS-CoV-2.

Impact of the COVID-19 Pandemic on Trauma Encounters.

OBJECTIVES: The Coronavirus Disease 2019 pandemic has affected the health care system significantly. We compare 2019 to 2020 to evaluate how trauma encounters has changed during the pandemic. METHODS: Retrospective analysis using a large US health care system to compare trauma demographics, volumes, mechanisms of injury, and outcomes. Statistical analysis was used to evaluate for significant differences comparing 2019 to 2020. RESULTS: Data was collected from 88 hospitals across 18 states. 169 892 patients were included in the study. There were 6.3% fewer trauma patient encounters in 2020 compared to 2019. Mechanism of injury was significantly different between 2019 and 2020 with less blunt injuries (89.64% vs. 88.39%, P < .001), more burn injuries (1.84% vs. 2.00%, P = .021), and more penetrating injuries (8.58% vs. 9.75%, P < .001). Compared to 2019, patients in 2020 had higher mortality (2.62% vs. 2.88%, P < .001), and longer hospital LOS (3.92 ± 6.90 vs. 4.06 ± 6.56, P < .001). CONCLUSION: The COVID-19 pandemic has significantly affected trauma patient demographics, LOS, mechanism of injury, and mortality.

MERS-CoV infection elicits long-lasting specific antibody, T and B cell immune responses in recovered individuals.

BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic zoonotic betacoronaviruses and a global public health concern. Better undersetting of the immune responses to MERS-CoV is needed to characterize the correlates of protection and durability of the immunity and to aid in developing preventative and therapeutic interventions. While MERS-CoV-specific circulating antibodies could persist for several years post-recovery, their waning raises concerns about their durability and role in protection. Nonetheless, memory B and T cells could provide long-lasting protective immunity despite the serum antibodies levels. METHODS: Serological and flow cytometric analysis of MERS-CoV-specific immune responses were performed on samples collected from a cohort of recovered individuals who required intensive care unit (ICU) admission as well as hospital or home isolation several years after infection to characterize the longevity and quality of humoral and cellular immune responses. RESULTS: Our data showed that MERS-CoV infection could elicit robust long-lasting virus-specific binding and neutralizing antibodies as well as T and B cell responses up to 6.9 years post-infection regardless of disease severity or need for ICU admission. Apart from the persistent high antibody titers, this response was characterized by B cell subsets with antibody-independent functions as demonstrated by their ability to produce TNF-α, IL-6, and IFN-γ cytokines in response to antigen stimulation. Furthermore, virus-specific activation of memory CD8+ and CD4+ T cell subsets from MERS-recovered patients resulted in secretion of high levels of TNF-α, IL-17 and IFN-γ. CONCLUSIONS: MERS-CoV infection could elicit robust long-lasting virus-specific humoral and cellular responses.

A Flipped-Based WebQuest Model as an Alternative Proposal for Students of English as a Foreign Language in the COVID-19 Era

To find alternative strategies to create meaningful learning for their students during COVID-19, teachers resorted to using digital tools. This paper aims at investigating the impact of the Flipped-Based WebQuest (FWQ) model on the improvement of English L2 writing competence among sixty-nine secondary education English as a Foreign Language (EFL) students in Egypt. The study adopted a quasi-experimental design with quantitative tools. Two groups of students were selected: a control group studying in the traditional way (face-to-face) and an experimental group learning English through FWQ. A pretest was used to assess students' L2 writing competence in both groups. After the intervention, a posttest was conducted to explore students' L2 writing skills gains in both groups. Additionally, a pre/post-anxiety questionnaire was used to check the effect of FWQ on decreasing L2 writing anxiety. The findings revealed that the FWQ model is effective in teaching English L2 writing skills and decreasing students' English L2 anxiety.

COVID-19 operational disruption and SMEs' performance: the moderating role of disruption orientation and government support

Purpose>Despite the growing unforeseen and catastrophic events that disrupt business operations, empirical studies on the impact of operational disruption (OD) on small and medium enterprises' (SMEs) performance dimensions are limited. The study aims to investigate the moderating effect of disruption orientation (DO) and government support (GS) on the relationship between coronavirus disease (COVID-19) OD and SMEs' performance.Design/methodology/approach>Quantitative survey method was used to collect data from 170 SMEs in Nigeria, through hand-delivery questionnaires. Partial least square (PLS) structural equation modeling (SEM) was employed to analyze the data.Findings>The result shows no significant relationship between COVID-19 OD, DO and GS with SMEs' financial performance (FP). However, the relationship between COVID-19 OD and non-financial performance (NFP) is negatively significant. The relationship between DO and NFP is positively significant. DO and GS have insignificant relationship with FP. Finally, DO and GS does not moderate any of the relationships between COVID-19 OD and the dimensions of SMEs' performance.Practical implications>The result implies that health-related disruptions such as COVID-19 affect only the NFP of SMEs. However, supply chain managers and SMEs are encouraged to adopt DO to enhance NFP of firms.Originality/value>The current study is the first to evaluate the impact of health-related disruptions on the two major dimensions of SMEs' performance (FP and NFP) by incorporating the moderating role of internal (DO) and external (GS) factors in to a single framework. However, the paper revealed new theoretical and practical knowledge by illuminating the absence of significant relationship between COVID-19 OD and SMEs' FP, implying that COVID-19 disruption does not significantly affect SMEs' FP.

Adding colchicine to tocilizumab in hospitalized patients with severe COVID-19 pneumonia: An open-label randomized controlled trial.

INTRODUCTION: Colchicine acts upstream in the cytokines cascade by inhibiting the nod-like receptor protein 3 (NLRP3) inflammasome while interleukin 6 (IL-6) receptor antagonists, such as tocilizumab, block the end result of the cytokines cascade. Hence, adding colchicine to tocilizumab with the aim of blocking the early and end products of the cytokines cascade, might reduce the risk of developing cytokine storm. METHODS AND ANALYSIS: We aim to conduct an open-label randomized controlled trial to evaluate the efficacy and safety of adding colchicine to tocilizumab among patients with severe COVID-19 pneumonia to reduce the rate of invasive mechanical ventilation and mortality. We will include patients with severe COVID-19 pneumonia who received tocilizumab according to our local guidelines. Enrolled patients will be then randomized in 1:1 to colchicine versus no colchicine. Patients will be followed up for 30 days. The primary outcome is the rate of invasive mechanical ventilation and will be determined using Cox proportional hazard model. DISCUSSION: Given colchicine's ease of use, low cost, good safety profile, and having different anti-inflammatory mechanism of action than other IL-6 blockade, colchicine might serve as a potential anti-inflammatory agent among patients with severe COVID-19 pneumonia. This study will provide valuable insights on the use of colchicine in severe COVID-19 when added to IL-6 antagonists. ETHICS AND DISSEMINATION: The Medical Research Center and Institutional Review Board at Hamad Medical Corporation in Qatar approved the study protocol (MRC-01-21-299). Results of the analysis will be submitted for publication in a peer-reviewed journal.

Effect of COVID-19 Pandemic on Neonatal Sepsis.

BACKGROUND: There is a sudden rise in infectious diseases, with special concern to the most recent SARS-CoV 2 outbreak. A retrospective study was conducted to study the effect of this outbreak on neonatal sepsis as a global issue that poses a challenge for pediatric management and to identify its risk factors, microbial profile, and mortality rate at King Faisal Medical Complex, Taif, KSA, a COVID-19-tertiary care segregation hospital. METHODS: This research included 111 neonates with a culture-proven diagnosis of neonatal sepsis (4 and 62 cases during 2019 and 2020, respectively). RESULTS: During 2019 early onset sepsis (EOS) occurred in 6/49 (12.2%) while in 2020 22/62 (35.5%), and during 2019 late onset sepsis (LOS) occurred in 43/49 (87.7%) while in 2020 40/62 (64.5%). Premature rupture of membrane was the major neonatal risk factor for EOS during 2019 and 2020 with proportions of 4 (66.7%), 20 (90.9%); respectively. As regards LOS, the peripherally inserted central catheters and peripheral lines were the top neonatal risk factors. In the two-year outbreak, the most prevalent causative organism for EOS neonates was Escherichia coli and for LOS neonates it was Klebsiella. There was non-significant change in the mortality rate of neonatal sepsis between 2019 and 2020. However, the mortality rate was higher in EOS 9/22 (40.9%) in 2020 in comparison to 2/6 (33.3%) in 2019. CONCLUSIONS: Neonatal sepsis remains a major health problem causing serious morbidity and mortality, and health care policy makers have to implement EOS preventive measures.

SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load.

Monitoring SARS-CoV-2 spread and evolution through genome sequencing is essential in handling the COVID-19 pandemic. Here, we sequenced 892 SARS-CoV-2 genomes collected from patients in Saudi Arabia from March to August 2020. We show that two consecutive mutations (R203K/G204R) in the nucleocapsid (N) protein are associated with higher viral loads in COVID-19 patients. Our comparative biochemical analysis reveals that the mutant N protein displays enhanced viral RNA binding and differential interaction with key host proteins. We found increased interaction of GSK3A kinase simultaneously with hyper-phosphorylation of the adjacent serine site (S206) in the mutant N protein. Furthermore, the host cell transcriptome analysis suggests that the mutant N protein produces dysregulated interferon response genes. Here, we provide crucial information in linking the R203K/G204R mutations in the N protein to modulations of host-virus interactions and underline the potential of the nucleocapsid protein as a drug target during infection.

An Updated Review on COVID-19.

Coronavirus Disease (COVID-19) pandemic has affected more than seven million individuals in 213 countries worldwide with a basic reproduction number ranging from 1.5 to 3.5 and an estimated case fatality rate ranging from 2% to 7%. A substantial proportion of COVID-19 patients are asymptomatic; however, symptomatic cases might present with fever, cough, and dyspnoea or severe symptoms up to acute respiratory distress syndrome. Currently, RNA RT-PCR is the screening tool, while bilateral chest CT is the confirmatory clinical diagnostic test. Several drugs have been repurposed to treat COVID-19, including chloroquine or hydroxychloroquine with or without azithromycin, lopinavir/ritonavir combination, remdesivir, favipiravir, tocilizumab, and EIDD-1931. Recently, Remdesivir gained FDA emergency approval based on promising early findings from the interim analysis of 1063 patients. The recently developed serology testing for SARSCoV-2 antibodies opened the door to evaluate the actual burden of the disease and to determine the rate of the population who have been previously infected (or developed immunity). This review article summarizes current data on the COVID-19 pandemic starting from the early outbreak, viral structure and origin, pathogenesis, diagnosis, treatment, discharge criteria, and future research.

Determinants of Obtaining COVID-19 Vaccination among Health Care Workers with Access to Free COVID-19 Vaccination: A Cross-Sectional Study.

INTRODUCTION: Despite global efforts to contain the illness, COVID-19 continues to have severe health, life, and economic repercussions; thus, maintaining vaccine development is mandatory. Different directions concerning COVID-19 vaccines have emerged as a result of the vaccine's unpredictability. AIMS: To study the determinants of the attitudes of healthcare workers (HCWs) to receiving or refusing to receive the vaccine. METHODS: The current study adopted an interviewed questionnaire between June and August 2021. A total of 341 HCWs currently working at Assiut University hospitals offered to receive the vaccine were included. RESULTS: Only half of the HCWs (42%) accepted the COVID-19 vaccine. The most common reason that motivated the HCWs was being more susceptible than others to infection (71.8%). On other hand, the common reasons for refusing included: previously contracted the virus (64.8%); did not have time (58.8%); warned by a doctor not to take it (53.8%). Nearly one-third of nonaccepting HCWs depended on television, the Internet, and friends who refused the vaccine for information (p < 0.05). In the final multivariate regression model, there were six significant predictors: sex, job category, chronic disease, being vaccinated for influenza, and using Assiut University hospital staff and the Ministry of Health as sources of information (p < 0.05). CONCLUSION: Misinformation and negative conceptions are still barriers against achieving the desired rate of vaccination, especially for vulnerable groups such as HCWs.

"The possible implication of endothelin in the pathology of COVID-19-induced pulmonary hypertension".

COVID-19 pandemic has changed the world dramatically since was first reported in Wuhan city, China [1]. Not only as a respiratory illness that could lead to fatal respiratory failure, but also some evidences suggest that it can propagate as a chronic disease associated with a variety of persistent post COVID-19 pathologies that affect patients' life [2,3]. Pulmonary hypertension (PH) is one of the challenging diseases that may develop as a consequence of SARS-COV-2 infection in some COVID-19 survivors [4,5]. The vasopressor, proliferative, proinflammatory, and prothrombotic actions of endothelin [6] may be encountered in the COVID-19-induced PH pathology. And so, endothelin blockers may have an important role to restrict the development of serious PH outcomes with special precautions considering patients with significant hypoxemia.

High Flow Nasal Therapy in Covid 19 Patient

TaibUVID nutritional supplements help rapid cure of COVID-19 infection and rapid reversion to negative nasopharyngeal swab PCR: for better public prophylaxis and treatment of COVID-19 pandemic.

Public prophylaxis to decrease the emergence of new daily COVID-19 cases is vital. Adjuvant TaibUVID nutritional supplements are promising home-made or hospital-made supplements suggested for rapidly preventing and treating COVID-19 pandemic. We report here a 44 years old male physician who caught COVID-19 infection at hospital in Egypt with confirmed positive nasopharyngeal swab PCR. Ethical committee approval and informed patient's consent were gained before performing this study. Chest X-ray revealed increased bronchovascular markings. Close follow-up was done with no treatment given and he was sent for home isolation. Few days later, he developed progressive non-productive cough and a sense of difficult breathing with no associated fever or chest pain. An antitussive drug was given to him. The patient read about TaibUVID supplements from social media and started to feel improvement after TaibUVID inhalation therapy (using the heated solution of nigella sativa and chamomile five times a day). He also received a home-made TaibUVID nutritional supplement (nigella sativa, chamomile and natural honey) five times daily for four consecutive days. The next day, he was quite better with mild symptoms. Two days later, nasopharyngeal swab PCR was negative while other patients still had positive nasopharyngeal swabs. As few attacks of mild cough and breathing difficulty existed, he was admitted to hospital. A nasopharyngeal swab PCR was done for him again and the result was negative also. Blood gases were normal. He had lymphocytosis (possibly due to TaibUVID effects) that counteract lymphopenia seen in COVID-19 patients. Biochemical and hematological evaluation were quite normal apart from increased serum chloride and lactate dehydrogenase. There was a mild decrease in serum CO2 and alkaline phosphatase. Chest CT report revealed symmetrically inflated both lungs with non-specific focal nodular infiltrates (scattered in basal and medial lung segments) in left lower lobes with faint ground glass opacities. He was discharged home. Few days later, he was quite improved with no symptoms and returned to his work comfortably. In conclusion, TaibUVID nutritional supplements may be effective in rapidly changing the nasopharyngeal swab PCR from positive to negative. TaibUVID nutritional supplements are advisable as a natural, safe and effective prophylaxis to stop COVID-19 infectiousness, transmission and emergence of new cases. Clinical studies to investigate TaibUVID nutritional benefits are strongly recommended. TaibUVID may be promising and recommended for public prophylaxis to decrease emergence of new COVID-19 cases.

Hospital preparedness and management of pediatric population during COVID-19 outbreak.

With the recent pandemic of Coronavirus disease-2019 (COVID-19), there has been a higher number of reported cases in children more than to the prior Corona Virus-related diseases, namely, severe acute respiratory syndrome and the Middle East respiratory syndrome. The rate of COVID-19 in children is lower than adults; however, due to high transmission rate, the number of reported cases in children has been increasing. With the rising numbers among children, it is imperative to develop preparedness plans for the pediatric population at the hospital level, departmental level, and patient care areas. This paper summarizes important considerations for pediatric hospital preparedness at the hospital level that includes workforce, equipment, supply; capacity planning, and infection prevention strategies, it also span over the management of COVID-19 pediatric patients in high-risk areas such as critical care areas, Emergency Department and operative rooms.

Identification of Atovaquone, Ouabain and Mebendazole as FDA Approved Drugs Tar-geting SARS-CoV-2 (Version 4) (preprint)

The newly emerged coronavirus, SARS-CoV-2, and the resulting COVID-19 disease, has spread swiftly across the globe since its initial detection in December 2019. Given the heavy toll of this pandemic, therapeutic options for treatment are urgently needed. Here, we adopted a repositioning approach using in-silico molecular modeling to screen FDA-approved drugs with established safety profiles for potential inhibitory effects against SARS-CoV-2. We used structure-based drug design to screen more than 2000 FDA approved drugs against SARS-CoV-2 main protease enzyme (Mpro) substrate-binding pocket, focusing on two potential sites (central and terminal sites) to identify hits based on their binding energies, binding modes, interacting amino acids, and therapeutic indications. We additionally screened the top hits from both sites for potential covalent binding via nucleophilic thiol attack of Cys 145. High-scoring candidates were then screened for antiviral activity against infectious SARS-CoV-2 in a cell-based viral replication assay, and counterscreened for toxicity. Atovaquone, Mebendazole, and Ouabain exhibited antiviral efficacy with IC50s well within their respective therapeutic plasma concentrations (low nanomolar to low micromolar range), and limited toxic effects. Notably, all three were predicted in docking studies to covalently bind SARS-CoV-2 Mpro, underscoring the utility of this in-silico approach for identifying putative antivirals for repurposing. These results do not confirm efficacy in animal models or in humans, but rather serve as a starting point for testing the antiviral potential of select FDA-approved drugs, either individually or in combination.

Identification of FDA Approved Drugs Targeting COVID-19 Virus by Structure-Based Drug Repositioning (Version 2) (preprint)

The new strain of Coronaviruses (SARS-CoV-2), and the resulting Covid-19 disease has spread swiftly across the globe after its initial detection in late December 2019 in Wuhan, China, resulting in a pandemic status declaration by WHO within 3 months. Given the heavy toll of this pandemic, researchers are actively testing various strategies including new and repurposed drugs as well as vaccines. In the current brief report, we adopted a repositioning approach using insilico molecular modeling screening using FDA approved drugs with established safety profiles for potential inhibitory effects on Covid-19 virus. We started with structure based drug design by screening more than 2000 FDA approved drugs against Covid-19 virus main protease enzyme (Mpro) substrate-binding pocket focusing on two potential sites (central and terminal sites) to identify potential hits based on their binding energies, binding modes, interacting amino acids, and therapeutic indications. In addition, we elucidate preliminary pharmacophore features for candidates bound to Covid-19 virus Mpro substrate-binding pocket. The top hits bound to the central site of Mpro substrate-binding pocket include antiviral drugs such as Darunavir, Nelfinavir and Saquinavir, some of which are already being tested in Covid-19 patients. Interestingly, one of the most promising hits in our screen is the hypercholesterolemia drug Rosuvastatin. In addition, the top hits bound to the terminal site of Mpro substrate-binding pocket include the anti-asthma drug Montelukast and the anti-histaminic Fexofenadine among others. These results certainly do not confirm or indicate antiviral activity, but can rather be used as a starting point for further in vitro and in vivo testing, either individually or in combination.