Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
• From Patent Search

From Preprints

• To what extent are Chinese international students in Leuven influenced by the educational thoughts of Confucius when coping with the Covid-19 pandemic situation? -
  The Chinese education market is the largest in Higher Education (HE) worldwide. The number of study-abroad Chinese students has experienced a constant growth throughout the previous decade. According to the Chinese Ministry of Education report, there were more than 660,000 Chinese students studying in different countries in 2018. This demonstrates the growing desire from Chinese students, as well as their parents, to integrate in multicultural contexts in order to broaden horizons in this modern era (Gao, 2018). However, recent studies revealed that Chinese overseas students have less affinity to different cultures and face many difficulties in integrating with students of different cultural backgrounds (Yu and Moskal, 2018). Both internal and external culture differences are the key factors behind Chinese students lacking ability for intercultural integration (Zhu and Gao, 2012), which is also associated with their difficulty in adapting in a different education system. Chinese overseas students come from a Confucian Heritage Culture where Confucianism has shaped the culture that has been deeply rooted in the Chinese education system. This has formed the students’ mind-set, resulting in certain personality traits related to social communication. Modesty, social and ritual propriety are the main tenets of Confucian traditionalism. It has become the standard for Chinese peoples’ social and moral behaviours, gives order to and strengthens the social connections between people. This mind-set influences Chinese international students’ cross-cultural communication, both in multilingual and multicultural contexts (Luo, Huang and Najjar, 2007). Taking the Covid-19 pandemic into consideration, it was observed that Chinese overseas students in different countries have proactively taken medical solutions for self-prevention in the crisis situation. In order to identify the role of Confucian Heritage Cultures influence in Chinese international students adapting to overseas education environments, this study examines the previous work on Confucian Heritage Culture involvement in Chinese education. It is designed to measure, to what extent are Chinese international students in Leuven influenced by Confucian Heritage Culture when coping with the Covid-19 pandemic situation during overseas study. The conducted thesis includes an academic review on Confucian Heritage Culture as a fundamental cultural factor in Chinese education system, a qualitative study and an analysis of Chinese international students in Leuven experience Confucian Heritage Culture to cope with lockdown situations. This thesis aims to explore the possible revelation of acculturation competence among Chinese international students within the coronavirus pandemic background.
  🖺 Full Text HTML: To what extent are Chinese international students in Leuven influenced by the educational thoughts of Confucius when coping with the Covid-19 pandemic situation?
• Comparative Immunogenicity, Safety and Efficacy Profiles of four COVID-19 Vaccine types in healthy adults: Systematic Review cum Meta-analysis of Clinical Trial data -

  Four principal types of authorised COVID-19 vaccines include inactivated whole-virus vaccines, protein subunit vaccines, viral-vector vaccines and nucleic acid (mRNA and DNA) vaccines. Despite numerous Randomised Controlled Trials (RCTs), comprehensive systematic review and comparative meta-analysis have not been performed to validate the immunogenicity, safety and efficacy of COVID-19 vaccines in the healthy adult population. We aim to fulfil this unmet void. We searched for peer-reviewed articles about RCTs of the COVID-19 vaccines on healthy adults (18-64 years) available in eight major bibliographic databases (PubMed, EMBASE, Web of Science, Cochrane Library, Scopus, ScienceDirect, POPLINE, HINARI) till August 28, 2022. The Risk of Bias (RoB) was assessed using the Cochrane RoB-2. Random effects meta-analysis was conducted by pooling dichotomous outcomes using risk ratios (safety outcomes) and continuous outcomes using standardised mean differences (immunogenicity outcomes). Efficacy outcomes were summarised narratively. Moderate to high-quality evidence suggests that those receiving COVID-19 vaccines had significantly higher immune responses compared to placebo. Serious adverse events were rare, confirming that COVID-19 vaccines were safe and immunogenic for the healthy adult population. Remarkably, adverse events were the least common in inactivated vaccines, and nucleic acid vaccines were the most immunogenic. The efficacies of COVID-19 vaccines ranged from 21.9% to 95.9% in preventing COVID-19. We endorse all four types of COVID-19 vaccines for public health policy implementing taskforces. Yet, meta-analyses based on individual patient data are warranted for more extensive measurement of differential impacts of COVID-19 vaccines on different genders, ethnicities, comorbidities and types of vaccine jabbed.

  🖺 Full Text HTML: Comparative Immunogenicity, Safety and Efficacy Profiles of four COVID-19 Vaccine types in healthy adults: Systematic Review cum Meta-analysis of Clinical Trial data
• Pan-antiviral effects of a PIKfyve inhibitor on respiratory virus infection in human nasal epithelium and mice -
  Endocytosis, or internalization through endosomes is a major cell entry mechanism used by respiratory viruses. Phosphoinositide 5-kinase (PIKfyve) is a critical enzyme for the synthesis of Phosphatidylinositol (3,5)biphosphate (PtdIns(3,5)P2), and has been implicated in virus trafficking via the endocytic pathway. In fact, antiviral effects of PIKfyve inhibitors against SARS-CoV-2 and Ebola have been reported, but there is little evidence regarding other respiratory viruses. In this study we demonstrated the antiviral effects of PIKfyve inhibitors on influenza virus and respiratory syncytial virus in vitro and in vivo. PIKfyve inhibitors, Apilimod mesylate (AM) and YM201636 concentration-dependently inhibited several influenza strains in a MDCK cell-cytopathic assay. AM also reduced the viral load and cytokine release, whilst improving the cell integrity of human nasal air liquid interface cultured epithelium infected with influenza PR8. In PR8-infected mice, AM (2mg/ml), when intranasally treated, exhibited significant reduction of viral load and inflammation and inhibited weight loss caused by influenza infection, with effects being similar to oral oseltamivir (10 mg/kg). In addition, AM demonstrated anti-viral effects in RSV A2 infected human nasal epithelium in vitro and mouse in vivo, with equivalent effect to that of ribavirin. AM also showed anti-viral effects against human rhinovirus and seasonal coronavirus in vitro. Thus, PIKfyve is found to be involved in influenza and RSV infection, and PIKfyve inhibitor is a promising molecule for pan-viral approach against respiratory viruses.
  🖺 Full Text HTML: Pan-antiviral effects of a PIKfyve inhibitor on respiratory virus infection in human nasal epithelium and mice
• Additive Manufacturing Leveraged Microfluidic Setup for Sample to Answer Colorimetric Detection of Pathogens -
  Colorimetric readout for the detection of infectious diseases is gaining traction at the point of care/need owing to its ease of analysis and interpretation, and integration potential with highly specific Loop-mediated amplification (LAMP) assays. However, coupling colorimetric readout with LAMP is rife with challenges including, rapidity, inter-user variability, colorimetric signal quantification, and user involvement in sequential steps of the LAMP assay, hindering its application. To address these challenges, for the first time, we propose a remotely smartphone-operated automated setup consisting of (i) an additively manufactured microfluidic cartridge, (ii) a portable reflected-light imaging setup with controlled epi-illumination (PRICE) module, and (iii) a control and data analysis module. The microfluidic cartridge facilitates sample collection, lysis, mixing of amplification reagents stored on-chip, and subsequent isothermal heating for initiation of amplification in a novel way by employing tunable elastomeric chambers and auxiliary components (heaters and linear actuators). PRICE offers a new imaging setup that captures the colorimetric change of the amplification media over a plasmonic nanostructured substrate in a controlled and noise-free environment for rapid minute-scale nucleic acid detection. The control and data analysis module employs microprocessors to automate cartridge operation in tandem with the imaging module. The different device components were characterized individually and finally, as a proof of concept, SARS-CoV-2 wild-type RNA was detected with a turnaround time of 13 minutes, showing the clinical feasibility. The suggested automated device can be adopted in future iterations for other detection and molecular assays that require sequential fluid handling steps.
  🖺 Full Text HTML: Additive Manufacturing Leveraged Microfluidic Setup for Sample to Answer Colorimetric Detection of Pathogens
• Pretrainable Geometric Graph Neural Network for Antibody Affinity Maturation -
  In the realm of antibody therapeutics development, increasing the binding affinity of an antibody to its target antigen is a crucial task. This paper presents GearBind, a pretrainable deep neural network designed to be effective for in silico affinity maturation. Leveraging multi-level geometric message passing alongside contrastive pretraining on protein structural data, GearBind capably models the complex interplay of atom-level interactions within protein complexes, surpassing previous state-of-the-art approaches on SKEMPI v2 in terms of Pearson correlation, mean absolute error (MAE) and root mean square error (RMSE). In silico experiments elucidate that pretraining helps GearBind become sensitive to mutation-induced binding affinity changes and reflective of amino acid substitution tendency. Using an ensemble model based on pretrained GearBind, we successfully optimize the affinity of CR3022 to the spike (S) protein of the SARS-CoV-2 Omicron strain. Our strategy yields a high success rate with up to 17-fold affinity increase. GearBind proves to be an effective tool in narrowing the search space for in vitro antibody affinity maturation, underscoring the utility of geometric deep learning and adept pre-training in macromolecule interaction modeling.
  🖺 Full Text HTML: Pretrainable Geometric Graph Neural Network for Antibody Affinity Maturation
• Waning of post-vaccination neutralizing antibody responses against SARS-CoV-2, a systematic literature review and meta-analysis -

  Background Mass COVID-19 vaccination and the continuous introduction of new viral variants of SARS-CoV-2, especially of Omicron subvariants, has resulted in an increase in the proportion of the population with hybrid immunity at various stages of waning protection. We systematically reviewed waning of post-vaccination neutralizing antibody titers in different immunological settings to investigate potential differences. Methods We searched for studies providing data for post-vaccination neutralizing antibody responses against SARS-CoV-2 in PubMed, bioRxiv, and medRxiv from Dec 15, 2021, to Jan 31, 2023, using keywords related to COVID-19, vaccination, and antibody neutralization. We used random effects meta-regression to estimate the average fold-reduction in post-vaccination neutralizing antibody titers against the Index strain or Omicron BA.1. from month 1 to month 6 post last dose, stratified by vaccination regimen (primary or booster) and infection-naive vs hybrid-immune status. Findings In total, 26 studies reporting longitudinal post-vaccination neutralizing antibody titers were included. Neutralization titers against the Index variant were available from all studies for infection-naive participants, and from nine for hybrid-immune participants. Against Omicron BA.1, nine and eight studies were available for infection-naive and hybrid-immune cohorts, respectively. In infection-naive cohorts, post-vaccination neutralization titers against the Index strain waned 5.1-fold (95% CI 3.4-7.8) from month 1 to month 6 following primary regimen and 3.8-fold (95% CI 2.4-5.9) following the booster. Titers against Omicron BA.1 waned 5.9-fold (95% CI 3.8-9.0) in infection-naive, post-booster cohorts. In hybrid-immune, post-primary vaccination cohorts, titers waned 3.7-fold (95% CI 1.7-7.9) against the Index strain and 5.0-fold (95% CI 1.1-21.8) against Omicron BA.1. Interpretation No obvious differences in waning between post-primary or post-boost vaccination were observed for vaccines used widely to date, nor between infection-naive and hybrid-immune participants. Titers against Omicron BA.1 may wane faster compared to Index titers, which may worsen for more recent Omicron sub-variants and should be monitored. Relatively small datasets limit the precision of our current analysis; further investigation is needed when more data become available. However, based on our current findings, striking differences in waning for the analyzed and future comparisons are unlikely.

  🖺 Full Text HTML: Waning of post-vaccination neutralizing antibody responses against SARS-CoV-2, a systematic literature review and meta-analysis
• Iterative In Silico Screening for Optimizing Stable Conformation of Anti-SARS-CoV-2 Nanobodies -
  Abstract–Nanobodies (Nbs or VHHs) are single-domain antibodies (sdAbs) derived from camelid heavy-chain antibodies. The variable region of these nanobodies has special and unique characteristics, such as small size, good tissue penetration, and cost-effective production, making nanobodies a good candidate for the diagnosis and treatment of viruses. Identifying effective nanobodies against the COVID-19 would help us defeat this dangerous virus or other unknown variants in future. Herein, we introduce an in silico screening strategy for optimizing stable conformation of anti-SARS-CoV-2 nanobodies. Firstly, various complexes containing nanobodies were downloaded from the RCSB database, which were identified from immunized llamas. The primary docking between nanobodies and the SARS-CoV-2 spike protein receptor-binding domain was performed through ClusPro program, with the manually screening that leaving the reasonable conformation to the next step. Then, the binding distances of atoms between the antigen-antibody interfaces was measured through the Neighbor Search algorithm. Finally, filtered nanobodies were acquired according to HADDOCK scores through HADDOCK docking the Covid spike protein with nanobodies under restrictions of calculated molecular distance between active residues and antigenic epitopes less than 4.5 A. In this way, those nanobodies which with more reasonable conformation and with stronger neutralizing efficacy were acquired. This three-steps screening strategy iteratively in Silico greatly improved the accuracy of screening desired nanobodies compared to using only ClusPro docking or default HADDOCK docking settings. It provides new ideas for the screening of novel antibodies and computer-aided screening methods.
  🖺 Full Text HTML: Iterative In Silico Screening for Optimizing Stable Conformation of Anti-SARS-CoV-2 Nanobodies
• Development and Analytical Evaluation of a Point-of-Care Electrochemical Biosensor for Rapid and Accurate SARS-CoV-2 Detection -
  The COVID-19 pandemic has underscored the critical need for rapid and accurate screening and diagnostic methods for potential respiratory viruses. Existing COVID-19 diagnostic approaches face limitations either in terms of turnaround time or accuracy. In this study, we present an electrochemical biosensor that offers nearly instantaneous and precise SARS-CoV-2 detection, suitable for point-of-care and environmental monitoring applications. The biosensor employs a stapled hACE-2 N-terminal alpha helix peptide to functionalize an in-situ grown polypyrrole conductive polymer on a nitrocellulose membrane backbone through a chemical process. We assessed the biosensor's analytical performance using heat-inactivated omicron and delta variants of the SARS-CoV-2 virus in artificial saliva (AS) and nasal swabs (NS) samples diluted in a strong ionic solution. Virus identification was achieved through electrochemical impedance spectroscopy (EIS) and frequency analyses. The assay demonstrated a limit of detection of 40 TCID50/mL, with 95% sensitivity and 100% specificity. Notably, the biosensor exhibited no cross-reactivity when tested against the influenza virus. The entire testing process using the biosensor takes less than a minute. In summary, our biosensor exhibits promising potential in the battle against pandemic respiratory viruses, offering a platform for the creation of rapid, compact, portable, and point-of-care devices capable of multiplexing various viruses. This groundbreaking development has the capacity to significantly bolster our readiness and response to future viral outbreaks.
  🖺 Full Text HTML: Development and Analytical Evaluation of a Point-of-Care Electrochemical Biosensor for Rapid and Accurate SARS-CoV-2 Detection
• Enhanced Deep Convolutional Neural Network for SARS-CoV-2 Variants Classification -
  High-throughput sequencing techniques and sequence analysis have enabled the taxonomic classification of pathogens present in clinical samples. Sequencing provides an unbiased identification and systematic classification of pathogens and this is generally achieved by comparing novel sequences to pre-existing annotated reference databases. However, this approach is limited by large-scale reference databases which require considerable computational resources and skills to compare against. Alternative robust methods such as machine learning are currently employed in genome sequence analysis and classification, and it can be applied in classifying SARS-CoV-2 variants, whose continued evolution has resulted in the emergence of multiple variants. We developed a deep learning Convolutional Neural Networks-Long Short Term Memory (CNN-LSTM) model to classify dominant SARS-CoV-2 variants (omicron, delta, beta, gamma and alpha) based on gene sequences from the surface glycoprotein (spike gene). We trained and validated the model using > 26,000 SARS-CoV-2 sequences from the GISAID database. The model was evaluated using unseen 3,057 SARS-CoV-2 sequences. The model was compared to existing molecular epidemiology tool, nextclade. Our model achieved an accuracy of 98.55% on training, 99.19% on the validation and 98.41% on the test dataset. Comparing the proposed model to nextclade, the model achieved significant accuracy in classifying SARS-CoV-2 variants from unseen data. Nextclade identified the presence of recombinant strains in the evaluation data, a mechanism that the proposed model did not detect. This study provides an alternative approach to pre-existing methods employed in the classification of SARS-CoV-2 variants. Timely classification will enable effective monitoring and tracking of SARS-CoV-2 variants and inform public health policies in the control and management of the COVID-19 pandemic.
  🖺 Full Text HTML: Enhanced Deep Convolutional Neural Network for SARS-CoV-2 Variants Classification
• Open-source milligram-scale, four channel, automated protein purification system -
  Liquid chromatography purification of multiple recombinant proteins, in parallel, could catalyze research and discovery if the processes are fast and approach the robustness of traditional, "one-protein-at-a-time" purification. Here, we report an automated, four channel chromatography platform that we have designed and validated for parallelized protein purification at milligram scales. The device can purify up to four proteins (each with its own single column), has inputs for up to eight buffers or solvents that can be directed to any of the four columns via a network of software-driven valves, and includes an automated fraction collector with ten positions for 1.5 or 5.0 mL collection tubes and four positions for 50 mL collection tubes for each column output. The control software can be accessed either via Python scripting, giving users full access to all steps of the purification process, or via a simple-to-navigate touch screen graphical user interface that does not require knowledge of the command line or any programming language. Using our instrument, we report milligram-scale, parallelized, single-column purification of a panel of mammalian cell expressed coronavirus (SARS-CoV-2, HCoV-229E, HCoV-OC43, HCoV-229E) trimeric Spike and monomeric Receptor Binding Domain (RBD) antigens, and monoclonal antibodies targeting SARS-CoV-2 Spike (S) and Influenza Hemagglutinin (HA). We include a detailed hardware build guide, and have made the controlling software open source, to allow others to build and customize their own protein purifier systems.
  🖺 Full Text HTML: Open-source milligram-scale, four channel, automated protein purification system
• Parental intention, attitudes, beliefs, trust and deliberation towards childhood vaccination in the Netherlands in 2022: Indications of change compared to 2013 -

  Background and aim Vaccine uptake within the Dutch National Immunisation Programme (NIP) has slightly declined since the COVID-19 pandemic. We studied psychosocial factors of vaccine uptake, namely parental intention, attitudes, beliefs, trust and deliberation (i.e. self-evidence), before (2013) and two years into the pandemic (2022). Methods In 2022 and 2013, parents with a young child (aged <3.5 years) participated in online surveys on vaccination (n=1,000 and 800, (estimated) response=12.2% and 37.2%, respectively). Psychosocial factors were measured on 7-point Likert scales. Multivariate logistic regression analysis was used to study differences between parents in 2022 and 2013 in 9negative9 scores (≤2) of psychosocial factors. Results In both 2022 and 2013, most parents with a young child expressed positive intention (2022=83.1%, 2013=87.0%), attitudes (3 items: 2022=66.7%-70.9%, 2013=62.1%-69.8%) and trust (2022=51.8%, 2013=52.0%) towards the NIP and felt that vaccinating their child was self-evident (2022=57.2%, 2013=67.3%). Compared to parents with a young child in 2013, parents with a young child in 2022 had significantly higher odds of reporting negative attitudes towards vaccination (3 items combined: OR=2.84), believing that vaccinations offer insufficient protection (OR=4.89), that the NIP is not beneficial for the protection of their child9s health (OR=2.23), that vaccinating their child does not necessarily protect the health of other children (OR=2.24) or adults (OR=2.22) and that vaccinations could cause severe side effects (OR=2.20), preferring natural infection over vaccination (OR=3.18) and reporting low trust towards the NIP (OR=1.73). Conclusions Although most parents had positive intention, attitudes and trust towards vaccination and perceived vaccinating their child as self-evident, proportions of parents with negative scores were slightly larger in 2022 compared to 2013. Monitoring these determinants of vaccine uptake and developing appropriate interventions could contribute to sustaining high vaccine uptake.

  🖺 Full Text HTML: Parental intention, attitudes, beliefs, trust and deliberation towards childhood vaccination in the Netherlands in 2022: Indications of change compared to 2013
• Contact patterns of older adults with and without frailties in the Netherlands during the COVID-19 pandemic -

  Background During the COVID-19 pandemic social distancing measures were imposed to protect the population from exposure, especially older adults and persons with frailties who have the highest risk for severe outcomes. These restrictions greatly reduced contacts in the general population, but little is known about behaviour changes among older adults and persons with frailties themselves. Our aim was to quantify how COVID-19 measures affected contact behaviour of older adults and how this differed between older adults with and without frailties. Methods In 2021 a contact survey was carried out among persons aged 70 years and older in the Netherlands. A random sample of persons per age group (70-74, 75-79, 80-84, 85-89, 90+) and gender was invited to participate, either during a period with stringent (April 2021) or moderate (October 2021) measures. Participants provided general information on themselves including their frailty, and they reported characteristics of all persons with whom they had face-to-face contact on a given day over the course of a full week. Results In total 720 community-dwelling elderly persons were included (overall response rate of 15%), who reported 16,505 contacts. During the survey period with moderate measures, participants without frailties had significantly more contacts outside their household than participants with frailties. Especially for females, frailty was a more informative predictor for number of contacts than age. During the survey period with stringent measures, participants with and without frailties had significantly lower numbers of contacts compared to the survey period with moderate measures. The reduction of number of contacts was largest for the eldest participants without frailties. As they interact mostly with adults of a similar high age who likely have frailties, this reduction of number of contacts indirectly protects older adults with frailties from SARS-CoV-2 exposure. Conclusions The results of this study reveal that social distancing measures during the COVID-19 pandemic differentially affected the contact patterns of older adults with and without frailties. The reduction of contacts may have led to direct protection of older adults in general but also to indirect protection of older adults with frailties.

  🖺 Full Text HTML: Contact patterns of older adults with and without frailties in the Netherlands during the COVID-19 pandemic
• An Energizing Role for Motivation in Information-Seeking During the Early Phase of the COVID- 19 Pandemic -
  Curiosity is a powerful determinant of behavior. The past decade has seen a surge of scientific research on curiosity, an endeavor recently imbibed with urgency by the WHO, which set managing information-seeking as a public health goal during pandemics. And yet, a fundamental aspect of curiosity has remained unresolved: its relationship to utility. Is curiosity a drive towards information simply for the sake of obtaining that information, or is it a rational drive towards optimal learning? We leveraged people’s curiosity about COVID-19 to study information-seeking and learning in a large sample (n=5376) during the spring of 2020. Our findings reveal that curiosity is goal-rational in that it maximizes the personal utility of learning. Personal utility, unlike normative economic utility, is contingent on a person’s motivational state. On the basis of these findings, we explain information-seeking during the pandemic with a rational theoretical framework for curiosity.
  🖺 Full Text HTML: An Energizing Role for Motivation in Information-Seeking During the Early Phase of the COVID- 19 Pandemic
• Verification Theatre at Borders and in Pockets -
  To appear in: Colleen M. Flood, Y.Y. Brandon Chen, Raywat Deonandan, Sam Halabi, and Sophie Thériault (eds.) Pandemics, Public Health, and the Regulation of Borders: Lessons from COVID-19 (Routledge, forthcoming). This version: August 2023. Abstract The COVID-19 pandemic saw the creation of a wide array of digital infrastructures, underpinning both digital and paper systems, for proving attributes such as vaccination, test results or recovery. These systems were hotly debated. Yet this debate often failed to connect their social, technical and legal aspects, focussing on one area to the exclusion of the others. In this paper, I seek to bring them together. I argue that fraud-free “vaccination certificate” systems were a technical and social pipe-dream, but one that was primarily advantageous to organisations wishing to establish and own infrastructure for future ambitions as verification platforms. Furthermore, attempts to include features to ostensibly reduce fraud had, and risks further, broader knock-on effects on local digital infrastructures around the world, particularly in countries with low IT capacities easily captured by large firms and de facto excluded from and by global standardisation processes. The paper further reflects on the role of privacy in these debates, and how privacy, and more specifically confidentiality, was misconstrued as a main design aim of these systems, when the main social problems could manifest even in a system built with state of the art privacy-enhancing technologies. The COVID-19 pandemic should sharpen our senses towards the importance of infrastructures, and more broadly, how to use technologies in societies in crises.
  🖺 Full Text HTML: Verification Theatre at Borders and in Pockets
• Transformative Effects of COVID-19 on Healthcare Systems -
  The global healthcare landscape has undergone an unprecedented metamorphosis due to the COVID-19 pandemic, revealing vulnerabilities, sparking innovation, and necessitating adaptive strategies. This crisis’s impact extends beyond immediate health concerns, influencing healthcare delivery, policy, and infrastructure. Healthcare systems faced overwhelming strain, resulting in improvised medical units and resource allocation shifts. The pandemic prompted the deferral of non-urgent medical procedures, while telehealth integration surged, reshaping patient-doctor interactions. Fragile supply chains underscored the need for enhanced resilience measures. Mental health challenges highlighted the importance of comprehensive care, and healthcare workers exhibited remarkable resilience. Collective efforts accelerated scientific advancements, yielding swift vaccine development. Existing health inequalities were exacerbated, underscoring the urgency of equitable healthcare provision. Policy reforms and global cooperation played pivotal roles. A paradigm shift emerged, emphasizing digital innovation in healthcare. The pandemic’s repercussions underscore the significance of adaptability, collaboration, and ensuring fair access to care.
  🖺 Full Text HTML: Transformative Effects of COVID-19 on Healthcare Systems

From Clinical Trials

• A Phase 2/3 Study to Evaluate the Safety and Immunogenicity of an (Omicron Subvariant) COVID-19 Vaccine Booster Dose of Previously Vaccinated Participants. - Condition:   COVID-19
  Interventions:   Biological: XBB.1.5 Vaccine (Booster);   Biological: XBB.1.5 Vaccine (single dose)
  Sponsor:   Novavax
  Not yet recruiting

• Effect of Natural Food on Gut Microbiome and Phospholipid Spectrum of Immune Cells in COVID-19 Patients - Condition:   COVID-19
  Intervention:   Dietary Supplement: Freeze-dried Mare Milk (Saumal)
  Sponsor:   Asfendiyarov Kazakh National Medical University
  Not yet recruiting

• EFFECT OF COGNITIVE BEHAVIORAL THERAPY ON DEPRESSION AND QUALITY OF LIFE IN PATIENTS WITH POST COVID-19 - Condition:   Post-COVID-19 Syndrome
  Intervention:   Behavioral: rehacom
  Sponsor:   Cairo University
  Enrolling by invitation

• Intradermal Administration of a COVID-19 mRNA Vaccine in Elderly - Conditions:   Vaccination; Infection;   COVID-19
  Intervention:   Biological: Comirnaty
  Sponsor:   Radboud University Medical Center
  Not yet recruiting

• A Safety and Immune Response Study to Evaluate Varying Doses of an mRNA Vaccine Against Coronavirus Disease 2019 (COVID-19) in Healthy Adults - Condition:   COVID-19
  Interventions:   Biological: mRNA-CR-04 vaccine 10μg;   Biological: mRNA-CR-04 vaccine 30μg;   Biological: mRNA-CR-04 vaccine 100μg;   Drug: Placebo
  Sponsor:   GlaxoSmithKline
  Not yet recruiting

• Phase 3 Adolescent Study for SARS-CoV-2 rS Variant Vaccines - Condition:   COVID-19
  Interventions:   Biological: NVX-CoV2601 co-formulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine;   Biological: Prototype/XBB.1.5 Bivalent Vaccine (5 µg)
  Sponsor:   Novavax
  Not yet recruiting

• Dietary Intervention to Mitigate Post-Acute COVID-19 Syndrome - Conditions:   Post-Acute COVID-19 Syndrome;   Fatigue
  Interventions:   Other: Dietary intervention to mitigate Post-Acute COVID-19 Syndrome;   Other: Attention Control
  Sponsor:   University of Maryland, Baltimore
  Not yet recruiting

• Hyperbaric on Pulmonary Functions in Post Covid -19 Patients. - Condition:   Post COVID-19 Patients
  Interventions:   Device: hyperbaric oxygen therapy;   Device: breathing exercise;   Drug: medical treatment
  Sponsor:   Cairo University
  Completed

• A Phase II Trial to Evaluate the Safety and Immunogenicity of BIMERVAX® When Coadministered With Seasonal Influenza Vaccine (SIIV) in Adults Older Than 65 Years of Age Fully Vaccinated Against COVID-19 - Conditions:   SARS CoV 2 Infection;   Influenza, Human
  Interventions:   Biological: BIMERVAX;   Biological: SIIV
  Sponsor:   Hipra Scientific, S.L.U
  Not yet recruiting

• Directed Topical Drug Delivery for Treatment for PASC Hyposmia - Condition:   Post Acute Sequelae Covid-19 Hyposmia
  Interventions:   Drug: Beclomethasone;   Other: Placebo;   Device: Microsponge
  Sponsor:   Duke University
  Not yet recruiting

• Supported Employment COVID-19 Rapid Testing for PWID - Condition:   Health Behavior
  Intervention:   Behavioral: Supported Employment
  Sponsor:   University of Oregon
  Not yet recruiting

• Telerehabilitation for Post COVID-19 Condition - Conditions:   Long COVID;   Chronic Fatigue Syndrome
  Intervention:   Other: Telerehabilitation program based on cardiorespiratory principles
  Sponsors:   Université de Sherbrooke;   Hotel Dieu Hospital
  Completed

• Study of Tixagevimab/Cilgavimab and Regdanvimab Efficacy for Treatment of COVID-19 - Condition:   Coronavirus Infections
  Interventions:   Drug: tixagevimab/cilgavimab 150+150 mg;   Drug: tixagevimab/cilgavimab 300+300 mg;   Drug: regdanvimab
  Sponsors:   City Clinical Hospital No.52 of Moscow Healthcare Department;   Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
  Active, not recruiting

• Immunogenicity and Safety of Concomitant Administration of Bivalent COVID-19 Vaccines With Influenza Vaccines - Conditions:   Immune Response;   Safety
  Interventions:   Biological: bivalent BNT162b2 mRNA original/omicron BA.4-5 vaccine;   Biological: quadrivalent influenza vaccine
  Sponsors:   Catholic Kwandong University;   Korea University Guro Hospital
  Active, not recruiting

• Getting INFORMED and Living Well Among Asian Americans in California - Conditions:   COVID-19;   Well-Being, Psychological
  Interventions:   Behavioral: INFORMED-Living Well;   Behavioral: Text Messaging Only
  Sponsors:   University of California, San Francisco;   Chinese Community Health Resource Center;   University of California, Davis;   University of California, Merced;   California Department of Public Health
  Not yet recruiting

From PubMed

• Spike protein mutations and structural insights of pangolin lineage B.1.1.25 with implications for viral pathogenicity and ACE2 binding affinity - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID -19, is constantly evolving, requiring continuous genomic surveillance. In this study, we used whole-genome sequencing to investigate the genetic epidemiology of SARS-CoV-2 in Bangladesh, with particular emphasis on identifying dominant variants and associated mutations. We used high-throughput next-generation sequencing (NGS) to obtain DNA sequences from COVID-19 patient samples and compared these…

• Identification of a drug binding pocket in TMEM16F calcium-activated ion channel and lipid scramblase - The dual functions of TMEM16F as Ca^(2+)-activated ion channel and lipid scramblase raise intriguing questions regarding their molecular basis. Intrigued by the ability of the FDA-approved drug niclosamide to inhibit TMEM16F-dependent syncytia formation induced by SARS-CoV-2, we examined cryo-EM structures of TMEM16F with or without bound niclosamide or 1PBC, a known blocker of TMEM16A Ca^(2+)-activated Cl^(-) channel. Here, we report evidence for a lipid scrambling pathway along a groove…

• CYP19A1 mediates severe SARS-CoV-2 disease outcome in males - Male sex represents one of the major risk factors for severe COVID-19 outcome. However, underlying mechanisms that mediate sex-dependent disease outcome are as yet unknown. Here, we identify the CYP19A1 gene encoding for the testosterone-to-estradiol metabolizing enzyme CYP19A1 (also known as aromatase) as a host factor that contributes to worsened disease outcome in SARS-CoV-2-infected males. We analyzed exome sequencing data obtained from a human COVID-19 cohort (n = 2,866) using a…

• Molnupiravir, a ribonucleoside antiviral prodrug against SARS-CoV-2, alters the voltage-gated sodium current and causes adverse events - Molnupiravir (MOL) is a ribonucleoside prodrug for oral treatment of COVID-19. Common adverse effects of MOL are headache, diarrhea, and nausea, which may be associated with altered sodium channel function. Here, we investigated the effect of MOL on voltage-gated Na^(+) current (I(Na)) in pituitary GH(3) cells. We show that MOL had distinct effects on transient and late I(Na), in combination with decreased time constant in the slow component of I(Na) inactivation. The 50% inhibitory…

• Expression and immunogenicity of recombinant porcine epidemic diarrhea virus Nsp9 - Porcine epidemic diarrhea virus (PEDV) causes acute diarrhea, vomiting, dehydration, and high mortality in newborn piglets, which leads to significant economic losses. Coronavirus nonstructural protein 9 (Nsp9) is an essential RNA binding protein for coronavirus replication, which renders it a promising candidate for developing antiviral drugs and diagnosis targeting PEDV. In this study, PEDV Nsp9 protein fused with MBP protein and His-tag were expressed and purified in Escherichia coli….

• Targeted Application of Functional Foods as Immune Fitness Boosters in the Defense against Viral Infection - In recent times, the emergence of viral infections, including the SARS-CoV-2 virus, the monkeypox virus, and, most recently, the Langya virus, has highlighted the devastating effects of viral infection on human life. There has been significant progress in the development of efficacious vaccines for the prevention and control of viruses; however, the high rates of viral mutation and transmission necessitate the need for novel methods of control, management, and prevention. In recent years, there…

• Phytochemical Profiling and Antiviral Activity of Green Sustainable Nanoparticles Derived from Maesa indica (Roxb.) Sweet against Human Coronavirus 229E - Plant secondary metabolites are key components for new, safe and effective drugs. Ethanolic extract of Maesa indica Roxb. Sweet (ME) aerial parts were used for biosynthesis of sustainable green zinc oxide nanoparticles (ZnO NPs) with an average particle size 6.80 ± 1.47 nm and zeta potential -19.7 mV. Both transmission electron microscopy and X-ray diffraction assay confirmed the hexagonal shape of ZnO NPs. Phenolic ingredients in ME were identified using LC-ESI-MS/MS-MRM revealing the…

• Characterization of Portulaca oleracea Whole Plant: Evaluating Antioxidant, Anticancer, Antibacterial, and Antiviral Activities and Application as Quality Enhancer in Yogurt - Purslane (Portulaca oleracea L.) is rich in phenolic compounds, protein, and iron. This study aims to produce functional yogurt with enhanced antioxidant, anticancer, antiviral, and antimicrobial properties by including safe purslane extract in yogurt formulation; the yogurt was preserved for 30 days at 4 °C, and then biochemical fluctuations were monitored. The purslane extract (PuE) had high phenolic compounds and flavonoids of 250 and 56 mg/mL, respectively. Therefore, PuE had considerable…

• Assessment of Purity, Stability, and Pharmacokinetics of NGP-1, a Novel Prodrug of GS441254 with Potential Anti-SARS-CoV-2 Activity, Using Liquid Chromatography - SARS-CoV-2 is a highly contagious and pathogenic virus that first appeared in late December 2019 and caused a global pandemic in a short period. The virus is a single-stranded RNA virus belonging to the Coronaviridae family. Numerous treatments have been developed and tested in response to the pandemic, particularly antiviral drugs. Among them, GS441524 (GS441), a nucleoside antiviral drug, has demonstrated promising results in inhibiting SARS-CoV-2. Nevertheless, the limited oral…

• A Comprehensive Technology Platform for the Rapid Discovery of Peptide Inhibitors against SARS-CoV-2 Pseudovirus Infection - We developed and validated a technology platform for designing and testing peptides inhibiting the infectivity of SARS-CoV-2 spike protein-based pseudoviruses. This platform integrates target evaluation, in silico inhibitor design, peptide synthesis, and efficacy screening. We generated a cyclic peptide library derived from the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and the angiotensin-converting enzyme 2 (ACE2) receptor. The cell-free validation process by ELISA…

• Mechanism and antibacterial synergies of poly(Dabco-BBAC) nanoparticles against multi-drug resistant Pseudomonas aeruginosa isolates from human burns - Multi-drug resistant bacteria are a major problem in the treatment of infectious diseases, such as pneumonia, meningitis, or even coronavirus disease 2019 (COVID-19). Cationic nanopolymers are a new type of antimicrobial agent with high efficiency. We synthesized and characterized cationic polymer based on 1,4-diazabicyclo [2.2.2] octane (DABCO) and Bis (bromoacetyl)cystamine (BBAC), named poly (DABCO-BBAC) nanoparticles(NPs), and produced 150 nm diameter NPs. The antibacterial activity of poly…

• Targeting RdRp of SARS-CoV-2 with De Novo Molecule Generation - Viruses are known for their extremely high mutation rates, allowing them to evade both the human immune system and many forms of standard medicine. Despite this, the RNA dependent RNA polymerase (RdRp) of the RNA viruses has been largely conserved, and any significant mutation of this protein is unlikely. The recent COVID-19 pandemic presents a need for therapeutics. We have designed a de novo drug design algorithm that generates strong binding ligands from scratch, based on only the structure…

• Regadenoson for the treatment of COVID-19: A five case clinical series and mouse studies - CONCLUSIONS: Infused RA is safe and produces rapid anti-inflammatory effects mediated by A2A adenosine receptors on iNKT cells and possibly in part by A2ARs on other immune cells and platelets. We speculate that iNKT cells are activated by release of injury-induced glycolipid antigens and/or alarmins such as IL-33 derived from virally infected type II epithelial cells which in turn activate iNKT cells and secondarily other immune cells. Adenosine released from hypoxic tissues, or RA infused as…

• Shedding light into the biological activity of aminopterin, via molecular structural, docking, and molecular dynamics analyses - In this study, the structural and anticancer properties of aminopterin, as well as its antiviral characteristics, were elucidated. The preferred conformations of the title molecule were investigated with semiempirical AM1 method, and the obtained the lowest energy conformer was then optimized by using density functional (DFT/B3LYP) method with 6-311++G(d,p) as basis set. The vibrational frequencies of the optimized structure were calculated by the same level of theory and were compared with the…

• Soluble wild-type ACE2 molecules inhibit newer SARS-CoV-2 variants and are a potential antiviral strategy to mitigate disease severity in COVID-19 - SARS-CoV-2, the virus responsible for COVID-19, has caused havoc around the world. While several COVID-19 vaccines and drugs have been authorised for use, these antiviral drugs remain beyond the reach of most low- and middle-income countries. Rapid viral evolution is reducing the efficacy of vaccines and monoclonal antibodies and contributing to deaths of some fully vaccinated persons. Others with normal immunity may have chosen not be vaccinated and remain at risk if they contract the…

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