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186 lines
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>02 February, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Metaproteomic analysis of nasopharyngeal swab samples to identify microbial peptides and potential co-infection status in COVID-19 patients</strong> -
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<div>
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Respiratory infections disrupt the microbiota in the upper respiratory tract (URT), putting patients at a risk for subsequent infections. During the pandemic, cases of COVID-19 were aggravated by secondary infections because of impaired immunity and medical interventions, which was clearly evident in the second wave of COVID-19 in India. The potential dangers and clinical difficulties of bacterial and fungal secondary infections in COVID-19 patients necessitate microbial exploration of the URT. In this regard, mass spectrometry (MS)-based proteome data of nasopharyngeal swab samples from COVID-19 patients was used to investigate the metaproteome. The MS datasets were searched against a comprehensive protein sequence database of common URT pathogens using multiple search platforms (MaxQuant, MSFragger, and Search GUI/PeptideShaker). The detected microbial peptides were verified using PepQuery, which analyses peptide-spectrum pairs to give statistical output for determining confident microbial peptides. Finally, a protein sequence database was generated using the list of verified microbial peptides for identification and quantitation of microbial peptides and proteins, respectively. The taxonomic analysis of the detected peptides revealed several opportunistic pathogens like Streptococcus pneumoniae, Rhizopus microsporus, Clavispora lusitaniae, and Syncephalastrum racemosum among others. Using parallel reaction monitoring (PRM), we validated a few identified microbial peptides in clinical samples. The analysis also revealed proteins belonging to species like Pseudomonas fluorescens, Enterobacter, and Clostridium to be up-regulated in severe COVID-19 samples. Thus, MS can serve as a powerful tool for untargeted detection of a wide range of microorganisms. Metaproteomic analysis in COVID-19 patients for early identification and characterisation of co-infecting microorganisms can significantly impact the diagnosis and treatment of patients.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.31.525328v1" target="_blank">Metaproteomic analysis of nasopharyngeal swab samples to identify microbial peptides and potential co-infection status in COVID-19 patients</a>
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</div></li>
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<li><strong>Neuron- and microglia-specific immunoexpression in steroid-independent male sexual behaviour in castrated B6D2F1 male mice</strong> -
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Sexual behaviour is necessary for procreation for several species and is traditionally viewed to be regulated by sex steroid hormones. However, several species exhibit steroid-independent sexual behaviour, and its molecular understanding is only beginning to be uncovered. The main goal of our experiment was to provide new insight into cell-specific roles that both neuronal and non-neuronal cells may play in steroid-independent male sexual behaviour. Forty B6D2F1 hybrid male mice underwent orchidectomy and were tested for reinstatement of steroid-independent male sexual behaviour after an extended period of social isolation caused by the COVID-19-mandated laboratory shutdown. After 62 weeks post-orchidectomy, 20.59% demonstrated reinstatement of steroid-independent male sexual behaviour (identified as ‘steroid-independent persistent maters’), while 23.53% of the males did not display steroid-independent male sexual behaviour (identified as ‘steroid-independent non-maters’). Using flow cytometry, we compared the preoptic area immunoexpression in NeuN+ neurons and Iba1+ microglia between steroid-independent persistent maters and steroid-independent non-maters (n = 5-6 per group). We found neuronal immunoexpression up-regulated for amyloid precursor protein and androgen receptor, as well as down-regulated for glucocorticoid receptor in steroid-independent persistent maters compared to steroid-independent non-maters. In conjunction, microglial immunoexpression of amyloid precursor protein was up-regulated in steroid-independent persistent maters compared to steroid-independent non-maters. These data suggest there are cell-specific immunoexpression differences, including the role of non-neuronal cells in steroid-independent male sexual behaviour.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.08.519640v2" target="_blank">Neuron- and microglia-specific immunoexpression in steroid-independent male sexual behaviour in castrated B6D2F1 male mice</a>
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</div></li>
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<li><strong>Increasingly divergent responses to infection in mice suggest B cell evolution is not constrained by germline-encoded specificities</strong> -
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Antibodies result from the competition of B cell lineages evolving under selection for improved antigen recognition, a process known as affinity maturation. High-affinity antibodies to pathogens such as HIV, influenza, and SARS-CoV-2 are frequently reported to arise from B cells whose receptors, the precursors to antibodies, are encoded by particular immunoglobulin alleles. This raises the possibility that the presence of particular germline alleles in the B cell repertoire is a major determinant of the quality of the antibody response. Alternatively, initial differences in germline alleles’ propensities to form high-affinity receptors might be overcome by chance events during affinity maturation. We first show how this can happen in simulations: even when fitness differences between germline alleles lead to similar allele usage across individuals early on, allele usage becomes increasingly dissimilar over time. We next find that mice experimentally infected with influenza virus demonstrate the same pattern of divergence in the weeks following infection. We investigated whether affinity maturation might nonetheless strongly select for particular amino acid motifs across diverse genetic backgrounds, but we found no evidence of convergence to similar CDR3 sequences or amino acid substitutions. These results suggest germline-encoded specificities might enable fast recognition of specific antigens early in the response, but diverse evolutionary routes to high affinity limit the genetic predictability of responses to infection and vaccination in the long term.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.16.508315v2" target="_blank">Increasingly divergent responses to infection in mice suggest B cell evolution is not constrained by germline-encoded specificities</a>
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<li><strong>Cryo-EM structures and binding of mouse and human ACE2 to SARS-CoV-2 variants of concern indicate that mutations enabling immune escape could expand host range</strong> -
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Investigation of potential hosts of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is crucial to understanding future risks of spillover and spillback. SARS-CoV-2 has been reported to be transmitted from humans to various animals after requiring relatively few mutations. There is significant interest in describing how the virus interacts with mice as they are well adapted to human environments, are used widely as infection models and can be infected. Structural and binding data of the mouse ACE2 receptor with the Spike protein of newly identified SARS-CoV-2 variants are needed to better understand the impact of immune system evading mutations present in variants of concern (VOC). Previous studies have developed mouse-adapted variants and identified residues critical for binding to heterologous ACE2 receptors. Here we report the cryo-EM structures of mouse ACE2 bound to trimeric Spike ectodomains of four different VOC: Beta, Omicron BA.1, Omicron BA.2.12.1 and Omicron BA.4/5. These variants represent the oldest to the newest variants known to bind the mouse ACE2 receptor. Our high-resolution structural data complemented with bio-layer interferometry (BLI) binding assays reveal a requirement for a combination of mutations in the Spike protein that enable binding to the mouse ACE2 receptor.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.19.504450v2" target="_blank">Cryo-EM structures and binding of mouse and human ACE2 to SARS-CoV-2 variants of concern indicate that mutations enabling immune escape could expand host range</a>
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<li><strong>Mucociliary Clearance Augmenting Drugs Block SARS-Cov-2 Replication in Human Airway Epithelial Cells</strong> -
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The coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2 coronavirus, is devastatingly impacting human health. A prominent component of COVID-19 is the infection and destruction of the ciliated respiratory cells, which perpetuates dissemination and disrupts protective mucociliary transport (MCT) function, an innate defense of the respiratory tract. Thus, drugs that augment MCT could improve barrier function of the airway epithelium, reduce viral replication and, ultimately, COVID-19 outcomes. We tested five agents known to increase MCT through distinct mechanisms for activity against SARS-CoV-2 infection using a model of human respiratory epithelial cells terminally differentiated in an air/liquid interphase. Three of the five mucoactive compounds tested showed significant inhibitory activity against SARS-CoV-2 replication. An archetype mucoactive agent, ARINA-1, blocked viral replication and therefore epithelial cell injury, thus, it was further studied using biochemical, genetic and biophysical methods to ascertain mechanism of action via improvement of MCT. ARINA-1 antiviral activity was dependent on enhancing the MCT cellular response, since terminal differentiation, intact ciliary expression and motion was required for ARINA-1-mediated anti-SARS-CoV2 protection. Ultimately, we showed that improvement of cilia movement was caused by ARINA-1-mediated regulation of the redox state of the intracellular environment, which benefited MCT. Our study indicates that Intact MCT reduces SARS-CoV-2 infection, and its pharmacologic activation may be effective as an anti-COVID-19 treatment.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.30.526308v1" target="_blank">Mucociliary Clearance Augmenting Drugs Block SARS-Cov-2 Replication in Human Airway Epithelial Cells</a>
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<li><strong>Structural prediction of chimeric immunogens to elicit targeted antibodies against betacoronaviruses</strong> -
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Betacoronaviruses pose an ongoing pandemic threat. Antigenic evolution of the SARS-CoV-2 virus has shown that much of the spontaneous antibody response is narrowly focused rather than broadly neutralizing against even SARS-CoV-2 variants, let alone future threats. One way to overcome this is by focusing the antibody response against better-conserved regions of the viral spike protein. Here, we present a design approach to predict stable chimeras between SARS-CoV-2 and other coronaviruses, creating synthetic spike proteins that display a desired conserved region and vary other regions. We leverage AlphaFold to predict chimeric structures and create a new metric for scoring chimera stability based on AlphaFold outputs. We evaluated 114 candidate spike chimeras using this approach. Top chimeras were further evaluated using molecular dynamics simulation as an intermediate validation technique, showing good stability compared to low-scoring controls. This demonstrates the feasibility of the underlying approach, which can be used to design custom immunogens to focus the immune response against a desired viral glycoprotein epitope.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.31.526494v1" target="_blank">Structural prediction of chimeric immunogens to elicit targeted antibodies against betacoronaviruses</a>
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<li><strong>Estimating measures to reduce the transmission of SARS-CoV-2 in Australia to guide a ‘National Plan’ to reopening</strong> -
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Background In mid-2021, widespread availability of COVID-19 vaccines with demonstrated impacts on transmission promised relief from the strict public health and social measures (PHSMs) imposed in many countries to limit spread and burden. We were asked to define vaccine coverage thresholds for transition through the stages of Australia9s 9National Plan9 to easing restrictions and reopening international borders. Methods Using available evidence of vaccine effectiveness against the then-circulating Delta variant, we used a mathematical model to determine vaccine coverage targets. The absence of any COVID-19 infections in many sub-national jurisdictions in Australia posed particular methodological challenges for modelling in this setting. We used a novel metric called Transmission Potential (TP) as a proxy measure of the population-level effective reproduction number. We estimated TP of the Delta variant under a range of PHSMs, test-trace-isolate-quarantine (TTIQ) efficiencies, vaccination coverage thresholds, and age-based vaccine allocation strategies. Findings We found that high coverage of vaccination across all age groups (≥ 70) combined with ongoing TTIQ and minimal PHSMs was sufficient to avoid strict lockdowns. At lesser coverage (≤ 60%) rapid case escalation risked overwhelming of the health sector and would prompt a need to reimpose strict restrictions, with substantive economic impacts in order to achieve the goals of the National Plan. Maintaining low case numbers was the most beneficial strategy for health and the economy, and at higher coverage levels (≥ 80%) further easing of restrictions was deemed possible. Interpretation These results reinforced recommendations from other modelling groups that some level of PHSMs should be continued to minimise the burden of the Delta variant following achievement of high population vaccine coverage. They directly informed easing of COVID-19 restrictions in Australia. Funding This study was supported by the Australian Government Department of Health and Ageing, and the National Health and Medical Research Council9s Centre of Research Excellence scheme (GNT1170960).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.15.22282869v3" target="_blank">Estimating measures to reduce the transmission of SARS-CoV-2 in Australia to guide a ‘National Plan’ to reopening</a>
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<li><strong>Fast and Accurate Maximum-Likelihood Estimation of Multi-Type Birth-Death Epidemiological Models from Phylogenetic Trees</strong> -
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Multi-type birth-death (MTBD) models are phylodynamic analogies of compartmental models in classical epidemiology. They serve to infer such epidemiological parameters as the average number of secondary infections R_e and the infectious time from a phylogenetic tree (a genealogy of pathogen sequences). The representatives of this model family focus on various aspects of pathogen epidemics. For instance, the birth-death exposed-infectious (BDEI) model describes the transmission of pathogens featuring an incubation period (when there is a delay between the moment of infection and becoming infectious, as for Ebola and SARS-CoV-2), and permits its estimation along with other parameters. With constantly growing sequencing data, MTBD models should be extremely useful for unravelling information on pathogen epidemics. However, existing implementations of these models in a phylodynamic framework have not yet caught up with the sequencing speed. Computing time and numerical instability issues limit their applicability to medium data sets (⩽ 500 samples), while the accuracy of estimations should increase with more data. We propose a new highly parallelizable formulation of ordinary differential equations for MTBD models. We also extend them to forests to represent situations when a (sub-)epidemic started from several cases (e.g. multiple introductions to a country). We implemented it for the BDEI model in a maximum likelihood framework using a combination of numerical analysis methods for efficient equation resolution. Our implementation estimates epidemiological parameter values and their confidence intervals in four minutes on a phylogenetic tree of 10 000 samples. Comparison to the existing implementations on simulated data shows that it is not only 30 000 times faster, but also more accurate. An application of our tool to the 2014 Ebola epidemic in Sierra-Leone is also convincing, with very fast calculation and precise estimates.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.02.22278328v3" target="_blank">Fast and Accurate Maximum-Likelihood Estimation of Multi-Type Birth-Death Epidemiological Models from Phylogenetic Trees</a>
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<li><strong>The Dark Side of Nurse Superhuman Narrative: Perspective from a Developing Country</strong> -
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Throughout human history, many people believed that there is a power beyond the normal realm that falls into either physical or super strength, spiritual and mental powers. Since then, people have always been captivated by the idea of having someone different from the normal one, which is indicated by their skills and abilities. A superhuman abilities perspective is characterized by having superior cognitive and perceptual capacities that are above normal humans, especially useful during times of crises and situations wherein life and death are the core subject of the occurrence. Angels and heroes are the common figures associated with having special superpowers that are beyond the usual, ordinary, and typical attributes of a person. Nurses are often associated with these superhuman traits and this narrative was magnified during the height of Covid-19 pandemic. This paper argues that this narrative is detrimental to both the discipline and profession of nursing.
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🖺 Full Text HTML: <a href="https://osf.io/3vew2/" target="_blank">The Dark Side of Nurse Superhuman Narrative: Perspective from a Developing Country</a>
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<li><strong>Caring-Based Curriculum Design in Helping & Healing Profession and Discipline: Theoretical Integration and Pedagogical Innovation in an Undergraduate Nursing Curriculum</strong> -
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The pandemic experience has brought up issues and concerns about the competencies of healthcare workers, especially those working in hospitals, especially nurses. The importance of caring, creating caring moments, and being a caring healthcare provider has been essential to all persons during the pandemic, whether Covid-19 afflicts them or not. Post-pandemic, the central question of, “are we educating nurses to be caring professionals or to be mere technicians?” needs more reflection as the realities of another pandemic emerging is well within the horizon. If caring is considered by many nurses as the essence of nursing and is fundamental to the nursing discipline and profession, how is it reflected in the current curriculum for an undergraduate degree in nursing? If it is not fully articulated as one of the basic requirements for the undergraduate curriculum in nursing, how do we functionally integrate it into our respective curriculum? These fundamental questions guide the flow and discussion of this paper as educating the next generation of nursing to explicitly express caring attributes in their professional practice rest upon the institution’s curricular development and innovations. As Smith & McCarthy (2010) greatly emphasized, the preparation of the next generations of nurses in the knowledge of the discipline of nursing will determine the potential for advancing the health of society through nursing’s unique contributions at a time of national healthcare crisis when they are most needed. This paper is composed of three distinct parts; first, the discourse of the philosophical and theoretical assumptions that serve as the grounding for curriculum innovation. Second is the exploration of the current context of caring in nursing education, emphasizing the need for the infusion of caring in the undergraduate nursing curriculum. Lastly, the presentation of the process by which caring is functionally integrated and fully articulated in the current BSN curriculum of San Beda University College of Nursing.
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🖺 Full Text HTML: <a href="https://osf.io/543wr/" target="_blank">Caring-Based Curriculum Design in Helping & Healing Profession and Discipline: Theoretical Integration and Pedagogical Innovation in an Undergraduate Nursing Curriculum</a>
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<li><strong>Evaluation of a Commercially Available Rapid RT-PCR Assay’s Detection of SARS-CoV-2 Novel Variants</strong> -
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Rapid molecular diagnostic tests have been critical in the response to the COVID-19 pandemic. It is important to evaluate the ability of these assays to identify variants of concern, particularly across varying collection and storage conditions. Nasal swabs positive for Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.167.2), Gamma (P.1), or Omicron (B.1.1.529) variants of concern (VOCs) were stored in TE buffer and viral transport media (VTM). We evaluated the sensitivity of the Cepheid Xpert® Xpress SARS-CoV-2 assay in detecting VOC samples and validated TE buffer for use with the assay. Testing of known VOC positives revealed no substantial reduction of PCR sensitivity. Comparison of TE and VTM samples also revealed no reduction in performance when using TE buffer, validating the use of TE buffer to store SARS-CoV-2 samples. SARS-CoV-2 VOCs collected and stored across various conditions can be detected by the Cepheid Xpert® Xpress SARS-CoV-2 assay.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.30.23285171v1" target="_blank">Evaluation of a Commercially Available Rapid RT-PCR Assay’s Detection of SARS-CoV-2 Novel Variants</a>
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<li><strong>Older age, lack of vaccination and infection with variants other than Omicron associated with severity of COVID-19 and in-hospital mortality in Pakistan</strong> -
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Objectives: We investigated factors associated with COVID-19 disease severity and in-hospital mortality in a low-middle income setting. Methods: Records of 197 adult COVID-19 patients admitted to the Aga Khan University Hospital, Karachi between April 2021 and February 2022 were reviewed. Clinical data including, that of SARS-CoV-2 variants was collected. Results: The median age of the patients was 55 years and 51.8% were males. 48.2 % of patients had non-severe disease, while 52.8% had severe/critical disease. Hypertension (48%) and diabetes mellitus (41.3%) were most common comorbid conditions. Omicron (55.3%), Beta (14.7%), Alpha (13.7%), Delta (12.7%) and Gamma (3.6%) were identified in patients. The risk of severe disease was higher in those aged above 50 years (OR 5.73; 95%CI [2.45-13.7]) and in diabetics (OR 4.24; 95% CI[1.82-9.85]). Full vaccination (OR 0.25; 95%CI [0.11-0.58]) or infection with Omicron variants (OR 0.42; 95% CI[0.23-0.74]) reduced disease severity. Age > 50 (OR 5.07; 95%CI [1.92-13.42]) and presence of myocardial infarction (OR 5.11; 95% CI[1.45-17.93]) was associated with increased mortality, but infection with Omicron (OR 0.22 95% CI 0.10-0.53]) reduced risk. Conclusions: Vaccination was found to protect against severe COVID-19 regardless of the infecting variant and is recommended especially, in those aged over 50 years and with co-morbid conditions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.30.23285170v1" target="_blank">Older age, lack of vaccination and infection with variants other than Omicron associated with severity of COVID-19 and in-hospital mortality in Pakistan</a>
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<li><strong>Sociodemographic and socioeconomic disparities in COVID-19 vaccine uptake - A nationwide record linkage study</strong> -
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Background: Recent studies have identified important social inequalities in SARS-CoV-2 infection and related COVID-19 outcomes in the Belgian population. The aim of our study was to investigate the sociodemographic and socioeconomic characteristics associated with the uptake of COVID-19 vaccine in Belgium. Methods: We conducted a cross-sectional analysis of the uptake of a first COVID-19 vaccine dose among 5,342,110 adults (≥18 years) in Belgium from December 28th 2020 (official starting date of the vaccination campaign) until August 31st 2021. We integrated data from four national data sources: the Belgian vaccine register (vaccination status), COVID-19 Healthdata (laboratory test results), DEMOBEL (sociodemographic/socioeconomic data), and the Common Base Registry for HealthCare Actors (individuals licensed to practice a healthcare profession in Belgium). We used multivariable logistic regression analysis for identifying characteristics associated with not having obtained a first COVID-19 vaccine dose in Belgium and for each of its three regions (Flanders, Brussels, and Wallonia). Results: During the study period, 10% (536,716/5,342,110) of the Belgian adult population included in our study sample was not vaccinated with a first COVID-19 vaccine dose. A lower COVID-19 vaccine uptake was found among young individuals, men, migrants, single parents, one-person households, and disadvantaged socioeconomic groups (with lower levels of income and education, unemployed). Overall, the sociodemographic and socioeconomic disparities were comparable for all regions. Conclusions: The identification of sociodemographic and socioeconomic disparities in COVID-19 vaccination uptake is critical to develop strategies guaranteeing a more equitable vaccination coverage of the Belgian adult population.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.31.23285233v1" target="_blank">Sociodemographic and socioeconomic disparities in COVID-19 vaccine uptake - A nationwide record linkage study</a>
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<li><strong>COVID-19 diagnostic testing underestimated cases amongst females in Pakistan</strong> -
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Objectives Understanding the impact of COVID-19 largely depended on information from PCR based diagnostic testing of SARS-CoV-2. It was recognized early in the pandemic that testing rates varied greatly between high and low income countries. Whilst total numbers of tests conducted are noted, little attention has been made to differences that may be due to gender and we examined this in the context of Pakistan. Methods We conducted a retrospective cross-sectional analysis of respiratory specimens received for SARS-CoV-2 by PCR at Aga Khan University Hospital, Karachi, Pakistan between February 2020 and February 2022. Data was analysed in six monthly intervals; P-I, February to July 2020; P-II, August 2020 to January 2021; P-III, February to July 2021 and August 2021 until February 2022. Results A total of 470,047 PCR tests were conducted. The proportion of tests conducted for females was, 35% in P-I; 40% in P-II; 44% in P-III and 46% in P-III. 21% of specimens were positive for SARS-CoV-2, only 9% of these specimens were from females. The greatest numbers of tests were conducted in males aged 31 to 45 years followed by those aged 16-30 years. The fewest tests were conducted in children aged under 15 years. The highest percentage of PCR positive tests was found in those ages 60 years and above. Compared for gender SARS-CoV-2 positivity rates were comparable across the study period. Conclusions COVID-19 data from Pakistan indicates that there are larger numbers of males as compared with females who were affected by this disease. Our results show that this may be due to a gender bias in the demographics of testing. This was especially true in the early pandemic period, leading to under- surveillance and -reporting of COVID-19 cases in females especially, in those of younger and older age groups.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.30.23285225v1" target="_blank">COVID-19 diagnostic testing underestimated cases amongst females in Pakistan</a>
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<li><strong>Road networks to explore COVID-19 infection</strong> -
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COVID-19 pandemic triggered an unprecedented level of restrictive measures globally. Most countries resorted to lockdowns at some point to buy the much-needed time for flattening the curve and scaling up vaccination and treatment capacity. Although lockdowns, social distancing and business closures generally slowed down the case growth, there is a growing concern about the social, economic and psychological impact of these restrictions, especially on the disadvantaged and poorer part of society. While we are all in this together, these segments are often taking the heavier toll of the pandemic and facing harsher restrictions or getting blamed for community transmission. This study tries to explore this perspective using quantitative analysis and network theory. The research is set in the context of the latest delta and omicron outbreaks in the Greater Sydney area, Australia, during late 2021. We first try to model how the local road networks between the neighbouring suburbs (i.e., neighbourhood measure) and current infection count affect the case growth and how they differ between delta and omicron variants. We use a geographic information system, population and infection data to measure road connections, mobility and transmission probability across the suburbs. We then looked at three socio-demographic variables: age, education and income and explored how they moderate independent and dependent variables (infection rates and neighbourhood measures). The result shows strong model performance to predict infection rate based on neighbourhood road connection. However, apart from age in the delta variant context, the other two variables (income and education level) do not seem to moderate the relation between infection rate and neighbourhood measure. The results indicate that suburbs with a more socio-economically disadvantaged population do not necessarily contribute to more community transmission. The study findings could be potentially helpful for stakeholders in tailoring any health decision for future pandemics.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.31.23285228v1" target="_blank">Road networks to explore COVID-19 infection</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase Ⅰ Clinical Trial of a Candidate COVID-19 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant COVID-19 Vaccine (chimpanzee adenovirus vector) for Inhalation<br/><b>Sponsors</b>: Wuhan BravoVax Co., Ltd.; National University Hospital, Singapore; Shanghai BravoBio Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Plitidepsin Versus Control in Immunocompromised Adult Participants With Symptomatic COVID-19 Requiring Hospital Care</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Plitidepsin<br/><b>Sponsor</b>: PharmaMar<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of Corfluvec Vaccine for the Prevention of COVID-19 in Healthy Volunteers</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Corfluvec component 1 low dose; Biological: Corfluvec component 2 low dose; Biological: Corfluvec component 1 high dose; Biological: Corfluvec component 2 high dose; Biological: Corfluvec low dose; Biological: Corfluvec high dose; Biological: Placebo<br/><b>Sponsors</b>: Tatyana Zubkova; MDP-CRO, LLC; St. Petersburg State Pavlov Medical University<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Self-testing Study</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: SMARTest mobile app for COVID-19 self-testing<br/><b>Sponsor</b>: Columbia University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of Efficacy and Safety of Azvudine vs. Nirmatrelvir-Ritonavir in the Treatment of COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Azvudine; Drug: Nirmatrelvir-Ritonavir<br/><b>Sponsors</b>: Shandong Provincial Hospital; Central hospital Affiliated to Shandong First Medical University; The Second Affiliated Hospital of Shandong First Medical University; The Affiliated Hospital Of Southwest Medical University; Gansu Provincial Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Low-Dose Radiation Therapy for Severe COVID-19 Pneumonia</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Radiation: Low-Dose Radiation Therapy<br/><b>Sponsors</b>: Jiangsu Cancer Institute & Hospital; Nanjing Chest Hospital; The Affiliated BenQ Hospital of Nanjing Medical University; Central South University; Zhongda Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Tetrandrine Tablets Used in Hospitalized Adults With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Tetrandrine<br/><b>Sponsor</b>: Peking University Third Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>INFLUENCE OF HIGH FREQUENCY CHEST WALL OSCILLATION IN HOSPITALIZED PATIENTS WITH COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: HIGH FREQUENCY CHEST WALL OSCILLATION<br/><b>Sponsor</b>: Cairo University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 2 Study to Evaluate the Efficacy and Safety of QLS1128 Orally in Symptomatic Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: QLS1128; Drug: Placebo<br/><b>Sponsor</b>: Qilu Pharmaceutical Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of Megadose Vitamin C in Severe and Critical Ill COVID-19 Patients.</strong> - <b>Conditions</b>: Vitamin C; COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: Vitamin C; Drug: Placebo<br/><b>Sponsor</b>: Zhujiang Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Difference Between Non-invasive High-frequency Oscillatory Ventilation and Non-invasive Continuous Airway Pressure Ventilation in COVID-19 With Acute Hypoxemia</strong> - <b>Conditions</b>: COVID-19 Pneumonia; Non-invasive Ventilation<br/><b>Interventions</b>: Device: Non-invasive high-frequency oscillatory ventilation; Device: Non-invasive continuous positive airway pressure ventilation<br/><b>Sponsor</b>: Guangzhou Institute of Respiratory Disease<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Molecular OTC At Home Test</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Diagnostic Test: Diagnostic Test: IN Vitro<br/><b>Sponsor</b>: 3EO Health<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Efficacy of the Therapy With BREINMAX® for the Treatment of Patients With Asthenia After COVID-19</strong> - <b>Conditions</b>: Asthenia; COVID-19<br/><b>Interventions</b>: Drug: Ethyl methyl hydroxypyridine succinate + Meldonium; Drug: Placebo<br/><b>Sponsor</b>: Promomed, LLC<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Aerosolized Versus Intravenous Colistin-based Antimicrobial Regimens in Hospitalized COVID-19 Patients With Bacterial Coinfection: A Randomized Controlled Trial</strong> - <b>Condition</b>: Secondary Bacterial Infection in COVID-19 Patients<br/><b>Intervention</b>: Drug: Colistin<br/><b>Sponsor</b>: Beni-Suef University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Acupuncture as an Adjunctive Therapy for Covid-19 Omicron Randomised Controlled Trial in Patients With Moderate/Severe Pneumonia</strong> - <b>Conditions</b>: Acupuncture; Covid-19 Omicron; Pulmonary Function<br/><b>Intervention</b>: Other: Acupuncture<br/><b>Sponsor</b>: The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron <em>in vivo</em></strong> - The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors</strong> - The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^(pro)) and papain like protease (PL^(pro)), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^(pro) inhibitors and 205 PL^(pro) inhibitors with low nmol/l activity of the best hits….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Kaempferol has potential anti-coronavirus disease 2019 (COVID-19) targets based on bioinformatics analyses and pharmacological effects on endotoxin-induced cytokine storm</strong> - COVID-19 has infected 272 million patients and caused 5.33 million deaths around the world, and it remains the main global threat. Previous studies revealed that Chinese traditional medicine is an effective treatment for COVID-19 infection. This study aims to reveal the pharmacological effects of kaempferol, which is the active component of Radix Bupleuri and Tripterygii Radix, and potential mechanisms for the treatment of COVID-19. Here, we employed the bioinformatics methods to filter the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Use of Iontophoresis Technology for Transdermal Delivery of a Minimal mRNA Vaccine as a Potential Melanoma Therapeutic</strong> - mRNA vaccines have attracted considerable attention as a result of the 2019 coronavirus pandemic; however, challenges remain regarding use of mRNA vaccines, including insufficient delivery owing to the high molecular weights and high negative charges associated with mRNA. These characteristics of mRNA vaccines impair intracellular uptake and subsequent protein translation. In the current study, we prepared a minimal mRNA vaccine encoding a tumor associated antigen human gp100(25-33) peptide…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Development of indolealkylamine derivatives as potential multi-target agents for COVID-19 treatment</strong> - COVID-19 is a complex disease with short-term and long-term respiratory, inflammatory and neurological symptoms that are triggered by the infection with SARS-CoV-2. As many drugs targeting single targets showed only limited effectiveness against COVID-19, here, we aimed to explore a multi-target strategy. We synthesized a focused compound library based on C2-substituted indolealkylamines (tryptamines and 5-hydroxytryptamines) with activity for three potential COVID-19-related proteins, namely…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>O</em>-GalNAc glycosylation affects the immunogenicity of the receptor-binding domain (RBD) of SARS-CoV-2 spike protein</strong> - The spike protein of SARS-CoV-2 has been widely used as an effective vaccine immunogen, although some limitations still remain. Herein, O-GalNAc glycosylated RBD (Tn-RBD) was synthesized as an antigen via in vitro glycosylation reactions. The inhibition ability against hACE2 binding of antibodies induced with Tn-RBD was 30-40% increased compared to that induced with RBD. This result implies that Tn-glycosylation might play important roles in the immunogenicity of the RBD protein, which should be…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of SARS-CoV-2 M<sup>pro</sup> with Vitamin C, L-Arginine and a Vitamin C/L-Arginine Combination</strong> - CONCLUSIONS: The findings of the current study are important because they help to identify COVID-19 treatments that are efficient, inexpensive, and have a favorable safety profile. The results of this study also suggest a possible adjuvant nutritional strategy for COVID-19 that could be used in conjunction with pharmacological agents.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Potential of Vouacapanes from <em>Pterodon emarginatus</em> Vogel Against COVID-19 Cytokine Storm</strong> - Purpose: The emergence of the COVID-19 pandemic has led to the search for potential therapeutic responses for various aspects of this disease. Fruits of Pterodon emarginatus Vogel (Fabaceae), sucupira, have been used in Brazilian traditional medicine because of their anti-inflammatory properties, which have been proven in vivo, in vitro, and in silico. Therefore, the aim of this work is to evaluate P. emarginatus oleoresin and isolated diterpenes by in vitro anti-inflammatory models. Methods: In…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bafilomycin A1 inhibits SARS-CoV-2 infection in a human lung xenograft mouse model</strong> - Coronavirus disease 2019 is a global pandemic caused by SARS-CoV-2. The emergence of its variant strains has posed a considerable challenge to clinical treatment. Therefore, drugs capable of inhibiting SARS-CoV-2 infection, regardless of virus variations, are in urgently need. Our results showed that the endosomal acidification inhibitor, Bafilomycin A1 (Baf-A1), had an inhibitory effect on the viral RNA synthesis of SARS-CoV-2, and its Beta and Delta variants at the concentration of 500 nM….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The impact of neutrophil extracellular traps in coronavirus disease - 2019 pathophysiology</strong> - Coronavirus disease 2019 (COVID-19), which is caused by novel coronavirus-2019 (nCoV-2019), is a highly contagious disease with high mortality and morbidity risk. Infected people may suffer from respiratory infections, which may be more progressive in patients with a defective immune system and underlying medical problems. In this regard, the cells involved in the innate immune system, play a decisive role in disease progression and complication development. Pathogen entrapment is the critical…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Traditional herbal compounds as candidates to inhibit the SARS-CoV-2 main protease: an <em>in silico</em> study</strong> - COVID-19, a disease caused by the SARS-CoV-2 virus, is responsible for a pandemic since March 2020 and it has no cure. Therefore, herein, different theoretical methods were used to obtain potential candidates from herbal compounds to inhibit the SARS-CoV-2 main protease (M^(pro)). Initially, the 16 best-scored compounds were selected from a library containing 4066 ligands using virtual screening by molecular docking. Among them, six molecules (physalin B 5,6-epoxide (PHY), methyl amentoflavone…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Minimalist Nanocomplex with Dual Regulation of Endothelial Function and Inflammation for Targeted Therapy of Inflammatory Vascular Diseases</strong> - Vascular disorders, characterized by vascular endothelial dysfunction combined with inflammation, are correlated with numerous fatal diseases, such as coronavirus disease-19 and atherosclerosis. Achieving vascular normalization is an urgent problem that must be solved when treating inflammatory vascular diseases. Inspired by the vascular regulatory versatility of nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) catalyzing l-arginine (l-Arg), the eNOS-activating effects of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Series of Adenosine Analogs as the First Efficacious Anti-SARS-CoV-2 Drugs against the B.1.1.529.4 Lineage: A Preclinical Repurposing Research Study</strong> - Given the rapid progression of the coronavirus disease 2019 (COVID-19) pandemic, an ultrafast response was urgently required to handle this major public crisis. To contain the pandemic, investments are required to develop diagnostic tests, prophylactic vaccines, and novel therapies. Lately, nucleoside analog (NA) antivirals topped the scene as top options for the treatment of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Meanwhile, the continuous…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The impact of loneliness on compliance with COVID-19 prevention guidelines</strong> - Many individuals have been reluctant to follow the COVID-19 prevention guidelines (e.g., wearing a mask, physical distancing, and vigilant handwashing) set forth by the U.S. Center for Disease Control to reduce the spread of COVID-19. In this research, we use reciprocal altruism theory to investigate the role of loneliness and its impact on compliance with these guidelines. Our findings indicate that lonely individuals are less willing to comply with COVID-19 prevention guidelines than…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>B cell response after SARS-CoV-2 mRNA vaccination in people living with HIV</strong> - CONCLUSIONS: The mRNA vaccination against SARS-CoV-2 elicits humoral and B cell responses quantitatively similar between PLWHIV and HCs, but there are important differences in terms of antibody functionality and phenotypes of memory B cells, reinforcing the notion that tailored vaccination policies should be considered for these patients.</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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