Protection of natural infection against reinfection with SARS-CoV-2 JN.1 variant (preprint)

This study investigated the effectiveness of natural infection in preventing reinfection with the JN.1 variant during a large JN.1 wave in Qatar, using a test-negative case-control study design. The overall effectiveness of previous infection in preventing reinfection with JN.1 was estimated at only 1.8% (95% CI: -9.3-12.6%). This effectiveness demonstrated a rapid decline over time since the previous infection, decreasing from 82.4% (95% CI: 40.9-94.7%) within 3 to less than 6 months after the previous infection to 50.9% (95% CI: -11.8-78.7%) in the subsequent 3 months, and further dropping to 18.3% (95% CI: -34.6-56.3%) in the subsequent 3 months. Ultimately, it reached a negligible level after one year. The findings show that the protection of natural infection against reinfection with JN.1 is strong only among those who were infected within the last 6 months, with variants such as XBB*. However, this protection wanes rapidly and is entirely lost one year after the previous infection. The findings support considerable immune evasion by JN.1.

The Rapidly Changing Patterns in Bacterial Co-infections Reveal Peaks in Limited Gram-Negatives during COVID and Their Sharp Drop Post- Vaccinations Implying Potential Evolution of Co-protection during Vaccine-Virus-Bacterial Interplay (preprint)

The SARS-CoV-2 have caused a devastating pandemic of all times in the recent human history. However, there is a serious paucity in high quality data on aggravating factors and mechanisms of co-infection. This study aimed to identify the trending patterns of bacterial co-infections and types and associated outcomes in three phases of the pandemic. Using quality hospital data, we have investigated the SARS-CoV-2 fatality rates, profiles, and types of bacterial co-infections before, during, and after COVID-19 vaccinations. Out of 389 isolates used in different aspects, 298 was examined before and during the pandemic (n=149 before, n=149 during), death rates were 32% during compared to only 7.4% before pandemic with significant association (P value = 0.000000075). Death rate was 34% in co-infected (n = 170) compared to non-co-infected patients (n = 128) indicating a highly significant value (P value = 0.00000000000088). However, analysis of patients without other respiratory problems (n=28) indicated that among the remaining 270 patients, death was 30% in co-infected patients (n=150) and only 0.8% in non-coinfected (n=120) with high significant P value= 0.00000000076. The trending patterns of co-infections before, during, and after vaccinations showed a significant decline in Staphylococcus aureus with concomitant peaks in Gram-negatives in totals of (n= 149 before/n= 149 during): Klebsiella pneumonia (n = 11/49 before/during; E. coli n=10/24, A. baumannii n=8/25, and Ps. Aeruginosa n= 5/16, and S. aureus 13/1. Nevertheless, in post vaccination phase, (n= 91) gender-specific co-infections were examined for potential differences in susceptibility. Methicillin resistant S. aureus (MRSA) dominated both genders followed by E. coli in males and females with the latter gender showing higher rates of isolations in both species. Klebsiella pneumoniae declined to third place mostly in male patients. The drastic decline in K. pneumoniae and Gram-negatives post-vaccination strongly imply a potential co-protection in vaccines. Future analysis would gain more insights into molecular mimicry.

COVID-19 infection causes insulin-resistance between hospitalised patients in Najaf governorate

A novel epidemic infection Coronavirus-19 (COVID-19) considered as one of the challenges in sustainable development. A new-onset of hyperglycaemia has been observed between many COVID-19 patients. The clear explanation of this elevation in fasting plasma glucose (FPG) was debuted. Here we investigate whether this increase is due to impaired insulin secretion or insulin resistance. 269 participants, group 1 (control, n = 46) group 2 (COVID-19 patients, n = 223). 27 Patients were excluded due to missing of their FPG results. FPG, liver enzymes (ALT, AST, and Alk. Phosphatase), b.urea, s.creatinine, s. insulin, C-peptide, D-dimer, and s.ferritin were measured. Our results showed that FPG was increased in 82% (161) patients and this increase was positively correlated with ferritin (r20.039, P-value 0.0013). There is no correlation between FPG with liver enzymes (ALT and AST). The level of insulin hormone and c-peptide were normal. Because there were no increase in insulin or c-peptide and the only relationship was between FPG and ferritin. Therefore, we concluded that COVID-19 infection could cause insulin resistance. © 2023 Author(s).

Assessment of the challenges and adaptation strategies of pediatric nurses in charge of caring for children with COVID-19

Background: Coronavirus Disease 2019 (COVID-19) is a pandemic cause severe acute respiratory syndrome. It is a major public health crisis threatening humanity since world war two. Aim(s): This study aimed to assess challenges and adaptation strategies of pediatric nurses in charge of caring for children with COVID-19. Methodology: A descriptive research design was used to conduct this study. Setting(s): This study was carried out at pediatric hospital affiliated to Fayoum university hospitals. A purposive sample of 100 nurses who providing care for children with COVID-19 in the previous mentioned setting. A structured interview questionnaire sheet consisted of four parts were used for data collection: Part (1): Assess characteristics of studied sample;Part (2): Assess pediatric nurses' knowledge regarding caring for children with COVID-19;Part (3): Challenges that faced pediatric nurses in caring of children with COVID-19;Part (4): Adaptation strategies used by pediatric nurses to face of COVID-19 of children. Result(s): The results showed that 55% of the studied nurses had unsatisfactory knowledge level of caring for children with COVID-19. Regarding total challenges 75% of studied nurses had psychological challenges and 65% of the studied nurses had high working pressure. Also, regard adaptation strategy 60%, 55% and 51% of the studied nurses not used cognitive and educational adaptation, psychological and emotional adaptation and physical adaptation respectively. Conclusion(s): The present study concluded that, there was highly statistically significant between total challenges of COVID-19 and total adaptation strategies among pediatric nurses in charge of caring for children with COVID-19. Recommendations: Continuous training program for pediatric nurses to improve using of the adaptation strategies of caring for children during the COVID-19.Copyright © 2023 Scientific Publishers of India. All rights reserved.

Pre- and post-COVID-19 antimicrobial resistance profile of bacterial pathogens, a comparative study in a tertiary hospital.

INTRODUCTION: Antimicrobial resistance (AMR) is a natural evolutionary process in bacteria that is accelerated by selection pressure from the frequent and irrational use of antimicrobial drugs. This study aimed to determine the variations in AMR patterns of priority bacterial pathogens at a tertiary care hospital in the Gaza Strip during pre- and post-COVID-19 pandemic. METHODOLOGY: This is a retrospective observational study to determine the AMR patterns of bacterial pathogens at a tertiary hospital in the Gaza Strip in the post-COVID-19 pandemic period compared to the pre-COVID-19 period. Positive-bacterial culture data of 2039 samples from pre-COVID-19 period and 1827 samples from post-COVID-19 period were obtained from microbiology laboratory records. These data were analysed and compared by Chi square test using Statistical Package for Social Sciences (SPSS) Program. RESULTS: Gram-positive and Gram-negative bacterial pathogens were isolated. Escherichia coli was the most prevalent in both study periods. The overall AMR rate was high. There was a statistically significant increase in resistance to cloxacillin, erythromycin, cephalexin, co-trimoxazole and amoxicillin/clavulanic acid in the post-COVID-19 period compared to pre-COVID-19 period. There was also a significant decrease in resistance to cefuroxime, cefotaxime, gentamicin, doxycycline, rifampicin, vancomycin and meropenem in the post-COVID-19 period. CONCLUSIONS: During the COVID-19 pandemic, the AMR rates of restricted and noncommunity-used antimicrobials declined. However, there was an increase in AMR to antimicrobials used without medical prescription. Therefore, restriction on the sale of antimicrobial drugs by community pharmacies without a prescription, hospital antimicrobial stewardship and awareness about the dangers of extensive use of antibiotics are recommended.

Advanced Nonlinear Robust Approach for Controlling COVID-19 System Based on Vaccination Campaign

This study proposes a new approach for controlling COVID-19 through vaccination, where an adequately descriptive mathematical model is created for COVID-19 using the susceptible exposed infectious recovered (SEIR) model of epidemic diseases. The presented control approach is synthesized using a combination of feedback linearization and H∞ control, and incorporates model reference control to achieve optimal time responses with the aid of the black hole optimization (BHO) algorithm. The effectiveness of the designed control law is evaluated using data from the lombardy region of Italy. The results of the simulation show that the proposed control approach is able to effectively control the COVID-19 outbreak by accurately implementing the desirable vaccination, while effectively addressing nonlinearity and uncertainty in the COVID-19 system with a desirable control action. The control method has achieved the required immunity of 6.6 million individuals after approximately 25 days with a transmission rate reduced to zero in a short time, and a vaccination rate of 170 thousand people per day © 2023, International Journal of Intelligent Engineering and Systems.All Rights Reserved.

Potential role of PIM1 inhibition in the treatment of SARS-CoV-2 infection.

BACKGROUND: SARS-CoV-2 infection involves disturbing multiple molecular pathways related to immunity and cellular functions. PIM1 is a serine/threonine-protein kinase found to be involved in the pathogenesis of several viral infections. One PIM1 substrate, Myc, was reported to interact with TMPRSS2, which is crucial for SARS-CoV-2 cell entry. PIM1 inhibitors were reported to have antiviral activity through multiple mechanisms related to immunity and proliferation. This study aimed to evaluate the antiviral activity of 2-pyridone PIM1 inhibitor against SARS-CoV-2 and its potential role in hindering the progression of COVID-19. It also aimed to assess PIM1 inhibitor's effect on the expression of several genes of Notch signaling and Wnt pathways. In vitro study was conducted on Vero-E6 cells infected by SARS-CoV-2 "NRC-03-nhCoV" virus. Protein-protein interaction of the study genes was assessed to evaluate their relation to cell proliferation and immunity. The effect of 2-pyridone PIM1 inhibitor treatment on viral load and mRNA expression of target genes was assessed at three time points. RESULTS: Treatment with 2-pyridone PIM1 inhibitor showed potential antiviral activity against SARS-CoV-2 (IC50 of 37.255 µg/ml), significantly lowering the viral load. Functional enrichments of the studied genes include negative regulation of growth rate, several biological processes involved in cell proliferation, and Interleukin-4 production, with interleukin-6 as a predicted functional partner. These results suggest an interplay between study genes with relation to cell proliferation and immunity. Following in vitro SARS-CoV-2 infection, Notch pathway genes, CTNNB1, SUMO1, and TDG, were found to be overexpressed compared to uninfected cells. Treatment with 2-pyridone PIM1 inhibitor significantly lowers the expression levels of study genes, restoring Notch1 and BCL9 to the control level while decreasing Notch2 and CTNNB1 below control levels. CONCLUSION: 2-pyridone PIM1 inhibitor could hinder cellular entry of SARS-CoV-2 and modulate several pathways implicated in immunity, suggesting a potential benefit in the development of anti-SARS-CoV-2 therapeutic approach.

Profiles of Independent-Comorbidity Groups in Senior COVID-19 Patients Reveal Low Fatality Associated with Standard Care and Low-Dose Hydroxychloroquine over Antivirals.

Introduction: The lack of feasible therapies and comorbidities aggravate the COVID-19 case-fatality rate (CFR). However, reports examining CFR associations with diabetes, concomitant cardiovascular diseases, chronic kidney disease, and chronic liver disease (CLD) are limited. More studies assessing hydroxychloroquine (Hcq) and antivirals are needed. Purpose: To examine associations of COVID-19 CFR in comorbid patient groups each with single comorbidities and after treatment with Hcq, favipiravir, and dexamethasone (Dex), either alone or in combination versus standard care. Methods: Using statistical analysis, we descriptively determined these associations among 750 COVID-19 patient groups during the last quarter of 2021. Results: A diabetes comorbidity (40%, n=299) showed twice the fatality (CFR 14%) of the others (CFR 7%; P=0.001). Hypertension (Htn) was the second-commonest comorbidity (29.5%, n=221), with similar CFR to diabetes (15% and 7% for Htn and non-Htn, respectively), but with higher significance (P=0.0006167). Although only 4% (n=30) heart failure (HF) was reported, the CFR (40%) was much higher than in those without it (8%). A similar rate (4%) for chronic kidney disease was reported, with CFRs of 33% and 9% among those with and without it, respectively (P=0.00048). Ischemic heart disease was 11% (n=74), followed by chronic liver disease (0.4%) and history of smoking (1%); however, these were not significant due to the sample sizes. Treatment indicated standard care and Hcq alone or in combination were superior (CFR of 4% and 0.5%, respectively) compared to favipiravir (25%) or Dex (38.5%) independently or in combination (35.4%). Furthermore, Hcq performed well (CFR 9%) when combined with Dex (9%; P=4.28-26). Conclusion: The dominance of diabetes and other comorbidities with significant association with CFR implied existence of a common virulence mechanism. The superiority of low-dose Hcq and standard care over antivirals warrants further studies.

Analysis and optimization of FFF process parameters to enhance the mechanical properties of 3D printed PLA products

Objectives: The present research aimed to assess the accuracy and precision of the TheraMon (R) microsensor embedded in different thicknesses of Hawley retainers (HR) for comparison with vacuum formed retainers (VFR).Methods: Thirty microsensors contained within different thicknesses and composition of retainers were divided into three equal groups: Group A thick coverage HR (3 mm), Group B thin coverage HR (1 mm), and Group C VFR (1 mm). The microsensors were immersed in thermostatic water at a controlled temperature of 35 degrees C, which corresponds to the average intra-oral temperature. After 1 week, data were gathered using the TheraMon (R) client software and analysed using ANOVA and Turkey's HSD tests.Results: All TheraMon (R) microsensors were functional and produced uninterrupted recordings during the 1-week test period. Thermal detection differed between the three removable retainer groups. A near accurate thermostatic water detection was noticed with the thin HR with a mean temperature of 34.81 +/- 0.04 degrees C, followed by VFR 34.77 +/- 0.09 degrees C, and finally the thick HR 34.73 +/- 0.05 degrees C (ANOVA p-value = 0.025). A between-group comparison showed a significant mean difference (MD) between the thin and thick HR groups (MD: 0.08, p-value = 0.01). However, there were no significant differences between VFR and neither the thick Hawley (MD: 0.04, p-value = 0.27) nor the thin Hawley group (MD:-0.03, p-value = 0.39).Conclusion: A removable retainer's variation in material thickness and composition could induce small but detectable changes in the precision of thermal detection by TheraMon (R) microsensors.

Evaluation of prognostic factors in management of associated COVID-19 oro-facial mucormycosis

After the declaration of coronavirus as a pandemic in 2019, a strong relationship has been shown between the sudden upsurge of mucormycosis occurrence in patients with history of COVID-19. This relation can be explained by the effect of coronavirus on the patient's immune system, the infection worsens the effect of the underlying predisposing factors such as diabetes mellitus and drugs therapies that were used in the treatment of COVID-19, especially corticosteroids. Mucormycosis presented mainly in patients who had comorbid conditions like diabetes, steroid therapy, or chemotherapy. This study showed the association between the increase in the prevalence of mucormycosis in patients with COVID-19 and proved that dia-betes was the main risk factor for this fungal infection. The study confirmed that many factors determined the prognosis in the management of mucormycosis, first of them is the early diagnosis which depends on a high index of clinical suspicion, accurate procedures for diagnosis confirmation such as biopsy, fungal culture media, radiological examination by computed tomography scan or magnetic resonance imaging, early initiation of antifungal therapy either Amphotericin-B or Liposomal Amphotericin-B as soon as the diagnosis is confirmed and aggressive surgical debridement of all infected tissues (Figure 1).

Forced to go online: A case study of learning consecutive and simultaneous interpreting under Covid-19 in Iraq

This paper explores the perspectives of Iraqi undergraduates studying consecutive and simultaneous interpreting (CI, SI) in the Department of Translation at Mustansiriyah University in Iraq following the sudden transition to the online environment due to Covid-19. The online mode of teaching and learning has never been adopted in Iraq before. This study, therefore, aims to investigate the challenges and opportunities that have emerged from this unprecedented experience of online learning. It does so by adopting a mixed-method approach combining an online survey and two online focus group sessions. We also conducted two online pilot experiments to test the feasibility of the Zoom app to teach CI and SI synchronously. The main findings of this study suggest that while a synchronous online learning environment would potentially contribute to enhancing interpreting skills, the online mode cannot totally replace actual classes in the Iraqi higher education context unless a rigorous infrastructure is first established. © 2023 University of Western Sydneys. All rights reserved.

Reuse of Sludge as Organic Soil Amendment: Insights into the Current Situation and Potential Challenges

Sludge generation as an organic by-product of wastewater treatment has seen a consistent increase worldwide due to population growth and industrial activities. This poses a chronic challenge regarding management options and environmental concerns. The agricultural valorization of unconventional organic materials has become inevitable, especially in semi-arid and arid countries that suffer from depleted soils and shortages in farm manure supply. High-income countries have also been interested in this recycling practice to mitigate landfilling or incineration issues. Sewage and some industrial sludges contain a complex mixture of beneficial and harmful substances, which varies with the origin of effluents. Therefore, sludge land application should be well managed in order to achieve sustainable agro-environmental goals. This review paper focuses on different aspects related to sludge reuse in agriculture, starting by investigating the diversity of sludge types and composition. In addition to the preponderant urban sewage sludge, the less-studied industrial sludges, such as those generated from pulp and paper mills or gas-to-liquid industries, are hereby addressed as well. Then, post-land application effects are discussed in relation to sludge quality, dose, and reuse conditions. The present paper also examines the disparities between guidelines that determine sludge conformity for land application in various countries or regions. Accordingly, special attention is given to increasing risks related to emerging pollutants in sludge such as pharmaceuticals, which have been overused since the outbreak of COVID-19 pandemic. This exhaustive investigation will assist the establishment of sustainable strategies for the safe agricultural reuse of biosolids.

Rapid rise in COVID-19 among young people in England - learning for the future.

OBJECTIVES: We determined the age and sociodemographic distribution of COVID-19 cases between January and September 2020 to identify the group with the highest incidence rates at the beginning of the second wave in England. STUDY DESIGN: We undertook a retrospective cohort study design. METHODS: SARS-CoV-2 cases in England were linked with area-level socio-economic status indicators using quintiles of the Index of Multiple Deprivation (IMD). Age-specific incidence rates were stratified by IMD quintile to further assess rates by area-level socio-economic status. RESULTS: Between July and September 2020, SARS-CoV-2 incidence rates were highest amongst those aged 18-21 years, reaching rates of 213.9 (18-19 years) and 143.2 (20-21 years) per 100,000 population by week ending 21 September 2022. Stratification of incidence rates by IMD quintile evidenced that despite high rates observed in the most deprived areas of England amongst the very young and older age groups, the highest rates were observed in the most affluent areas of England amongst the 18- to 21-year-olds. CONCLUSIONS: The reversal of sociodemographic trend in COVID-19 cases in England for those aged 18-21 years at the end of the summer of 2020 and beginning of the second wave showed a novel pattern of COVID-19 risk. For other age groups, the rates remained highest for those from more deprived areas, which highlighted persisting inequalities. Combined, this demonstrates the need to reinforce awareness of COVID-19 risk for young people, particularly given the late inclusion of the 16-17 years age group for vaccination administration, as well as continued efforts to reduce the impact of COVID-19 on vulnerable populations.

A pandemic within a pandemic? Admission to COVID-19 wards in hospitals is associated with increased prevalence of antimicrobial resistance in two African settings.

BACKGROUND: Patients who develop severe illness due to COVID-19 are more likely to be admitted to hospital and acquire bacterial co-infections, therefore the WHO recommends empiric treatment with antibiotics. Few reports have addressed the impact of COVID-19 management on emergence of nosocomial antimicrobial resistance (AMR) in resource constrained settings. This study aimed to ascertain whether being admitted to a COVID-19 ward (with COVID-19 infection) compared to a non-COVID-19 ward (as a COVID-19 negative patient) was associated with a change in the prevalence of bacterial hospital acquired infection (HAI) species or resistance patterns, and whether there were differences in antimicrobial stewardship (AMS) and infection prevention and control (IPC) guidelines between COVID-19 and non-COVID-19 wards. The study was conducted in Sudan and Zambia, two resource constrained settings with differing country-wide responses to COVID-19. METHODS: Patients suspected of having hospital acquired infections were recruited from COVID-19 wards and non-COVID-19 wards. Bacteria were isolated from clinical samples using culture and molecular methods and species identified. Phenotypic and genotypic resistance patterns were determined by antibiotic disc diffusion and whole genome sequencing. Infection prevention and control guidelines were analysed for COVID-19 and non-COVID-19 wards to identify potential differences. RESULTS: 109 and 66 isolates were collected from Sudan and Zambia respectively. Phenotypic testing revealed significantly more multi-drug resistant isolates on COVID-19 wards in both countries (Sudan p = 0.0087, Zambia p = 0.0154). The total number of patients with hospital acquired infections (both susceptible and resistant) increased significantly on COVID-19 wards in Sudan, but the opposite was observed in Zambia (both p = ≤ 0.0001). Genotypic analysis showed significantly more ß-lactam genes per isolate on COVID-19 wards (Sudan p = 0.0192, Zambia p = ≤ 0.0001). CONCLUSIONS: Changes in hospital acquired infections and AMR patterns were seen in COVID-19 patients on COVID-19 wards compared to COVID-19 negative patients on non-COVID-19 wards in Sudan and Zambia. These are likely due to a potentially complex combination of causes, including patient factors, but differing emphases on infection prevention and control, and antimicrobial stewardship policies on COVID-19 wards were highlighted.

Development of thermosensitive hydrogel of Amphotericin-B and Lactoferrin combination-loaded PLGA-PEG-PEI nanoparticles for potential eradication of ocular fungal infections: In-vitro, ex-vivo and in-vivo studies

The most prevalent conditions among ocular surgery and COVID−19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co-loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo. The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections. Graphical Unlabelled Image

A New Polymorphic Comprehensive Model for COVID-19 Transition Cycle Dynamics with Extended Feed Streams to Symptomatic and Asymptomatic Infections

This work presents a new polymorphic, reusable, and comprehensive mathematical model for COVID-19 epidemic transition cycle dynamics. This model has the following characteristics: (1) The core SEIR model includes asymptomatic and symptomatic infections;(2) the symptomatic infection is a multi-variant;(3) the recovery stage provides a partial feed to the symptomatic infection;and (4) the symptomatic and asymptomatic stages have additional feed streams from the protected stage. The proposed formalisation template is a canonical way to achieve different models for the underlying health control environment. This template approach endows the model with polymorphic and reusable capability across different scenarios. To verify the model's reliability and validity, this work utilised two sets of initial conditions: date range and COVID-19 data for Canada and Saudi Arabia. © 2023 by the authors.

Development of thermosensitive hydrogel of Amphotericin-B and Lactoferrin combination-loaded PLGA-PEG-PEI nanoparticles for potential eradication of ocular fungal infections: In-vitro, ex-vivo and in-vivo studies.

The most prevalent conditions among ocular surgery and COVID-19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co-loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo. The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections.

Population immunity of natural infection, primary-series vaccination, and booster vaccination in Qatar during the COVID-19 pandemic: An observational study (preprint)

Background: Waning of natural infection protection and vaccine protection highlight the need to evaluate changes in population immunity over time. Population immunity of previous SARS-CoV-2 infection or of COVID-19 vaccination are defined, respectively, as the overall protection against reinfection or against breakthrough infection at a given point in time in a given population. Methods: We estimated these population immunities in Qatar population between July 1, 2020 and November 30, 2022, to discern generic features of the epidemiology of SARS-CoV-2. Effectiveness of previous infection, mRNA primary-series vaccination, and mRNA booster (third-dose) vaccination in preventing infection were estimated, month by month, using matched, test-negative, case-control studies. Findings: Previous-infection effectiveness against reinfection was strong before emergence of Omicron, but declined with time after a wave and rebounded after a new wave. Effectiveness dropped immediately after Omicron emergence from 88.3% (95% CI: 84.8-91.0%) in November 2021 to 51.0% (95% CI: 48.3-53.6%) in December 2021. Primary-series effectiveness against infection was 84.0% (95% CI: 83.0-85.0%) in April 2021, soon after introduction of vaccination, before waning gradually to 52.7% (95% CI: 46.5-58.2%) by November of 2021. Effectiveness declined linearly by ~1 percentage point every 5 days. After Omicron emergence, effectiveness dropped suddenly from 52.7% (95% CI: 46.5-58.2%) in November 2021 to negligible levels in December 2021. Booster effectiveness dropped immediately after Omicron emergence from 83.0% (95% CI: 65.6 -91.6%) in November 2021 to 32.9% (95% CI: 26.7-38.5%) in December 2021, and continued to decline thereafter. Effectiveness of previous infection and vaccination against severe, critical, or fatal COVID-19 were generally >80% throughout the study duration. Interpretation: High population immunity may not be sustained beyond a year. This creates fertile grounds for repeated waves of infection to occur, but these waves may increasingly exhibit a benign pattern of infection. Funding: The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, Qatar University Biomedical Research Center, and Qatar University Internal Grant ID QUCG-CAS-23/24-114.

Association between Multimorbidity and COVID-19 Mortality in Qatar: A Cross-Sectional Study

This study assessed the association between multimorbidity and mortality from COVID-19 in the Middle East and North Africa region, where such data are scarce. We conducted a cross-sectional study using data of all cases with COVID-19 reported to the Ministry of Public Health of Qatar from March to September 2020. Data on pre-existing comorbidities were collected using a questionnaire and multimorbidity was defined as having at least two comorbidities. Proportions of deaths were compared by comorbidity and multimorbidity status and multivariable logistic regression analyses were carried out. A total of 92,426 participants with a mean age of 37.0 years (SD 11.0) were included. Mortality due to COVID-19 was associated with gastrointestinal diseases (aOR 3.1, 95% CI 1.16-8.30), respiratory diseases (aOR 2.9, 95% CI 1.57-5.26), neurological diseases (aOR 2.6, 95% CI 1.19-5.54), diabetes (aOR 1.8, 95% CI 1.24-2.61), and CVD (aOR 1.5, 95% CI 1.03-2.22). COVID-19 mortality was strongly associated with increasing multimorbidity;one comorbidity (aOR 2.0, 95% CI 1.28-3.12), two comorbidities (aOR 2.8, 95% CI 1.79-4.38), three comorbidities (aOR 6.0, 95% 3.34-10.86) and four or more comorbidities (aOR 4.15, 95% 1.3-12.88). This study demonstrates a strong association between COVID-19 mortality and multimorbidity in Qatar.

Are parents' willing to vaccinate their children against COVID-19? A qualitative study based on the Health Belief Model.

In response to the COVID-19 pandemic, several countries have started implementing voluntary or involuntary mass vaccination programs. Although vaccine acceptance is high among adults, uncertainty about whether to vaccinate children against COVID-19 remains a controversial theme. To date, few qualitative studies have explored parents' views on this topic. A qualitative descriptive study design was used to collect data and individual in-depth interviews were conducted with 50 parents in the Makkah region of Saudi Arabia. The Health Belief Model (HBM) was used as a guide in developing the interview guide. Each question was related to a construct of the HBM. The data were then analyzed using thematic content analysis and interpreted using NVivo software. Two major themes emerged: motivation to vaccinate children, which was influenced by perceived benefits, perceived severity, perceived suitability, collective responsibilities, confidence, and cues to action; and barriers to vaccination in children, which included complacency, rapid vaccine development, and uncertainty about the long-term side effects of the vaccine. The findings of this study revealed that the public is not sufficiently informed about the efficacy or side effects of the COVID-19 vaccine, increasing the awareness of which will help parents make informed decisions regarding vaccinating their children and potentially increase vaccine acceptance.

Currently, the debate about whether children should be vaccinated for COVID-19 is ongoing worldwide. This research explored the thoughts of Saudi Arabian parents in this regard through in-depth interviews. The viewpoints were grouped into two themes: motivators and barriers toward vaccination. The motivators included factors such as parents' beliefs that the vaccine would help protect their children and the aged against the severity of the disease, especially those with existing conditions such as obesity. They also felt that the vaccination would help develop the society's herd immunity against the virus and felt an obligation to have their children vaccinated. Barriers toward vaccination included factors such as concerns about the long-term side effects of the vaccine on children, and the belief that children's immune systems are strong enough to fight the virus and that the vaccine might negatively affect their immune systems. This study showed that parents need to be educated on the benefits and side effects of COVID-19 vaccination for children. The results of this study will help health authorities and the government to increase the uptake and acceptability of the COVID-19 vaccine for children.