192 lines
49 KiB
HTML
192 lines
49 KiB
HTML
<!DOCTYPE html>
|
||
<html lang="" xml:lang="" xmlns="http://www.w3.org/1999/xhtml"><head>
|
||
<meta charset="utf-8"/>
|
||
<meta content="pandoc" name="generator"/>
|
||
<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
|
||
<title>19 July, 2022</title>
|
||
<style type="text/css">
|
||
code{white-space: pre-wrap;}
|
||
span.smallcaps{font-variant: small-caps;}
|
||
span.underline{text-decoration: underline;}
|
||
div.column{display: inline-block; vertical-align: top; width: 50%;}
|
||
</style>
|
||
<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>
|
||
<body>
|
||
<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
|
||
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
|
||
<ul>
|
||
<li><a href="#from-preprints">From Preprints</a></li>
|
||
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
|
||
<li><a href="#from-pubmed">From PubMed</a></li>
|
||
<li><a href="#from-patent-search">From Patent Search</a></li>
|
||
</ul>
|
||
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
|
||
<ul>
|
||
<li><strong>Corpus-based Studies of Metaphor: An Overview</strong> -
|
||
<div>
|
||
The researchers performed this systematic review to offer insights into the trend of the corpus-based approach in studying metaphor in recent years and investigate the potential gaps and under-researched areas in the past literature on the topic. Two research databases, namely Google Scholar and Academics, were explored to collect data. The analysis of metaphor-related research studies published between 2015 and 2020 revealed more than 78 studies dealing with the topic of investigation. After the screening process, 23 studies that met the research criteria were retained for analysis. The selected articles were further analyzed using the two-step analysis involving quantitative and qualitative approaches, i.e., descriptive statistics, and thematic analysis. The findings revealed that metaphor studies employing the corpus approach tend to use existing corpus like the Reference Corpus instead of a specialized corpus. In addition, metaphor studies in this review centered more on written discourse than spoken data. Furthermore, there is also a lack of information on the corpus tool employed in the examined studies. Meanwhile, the thematic analysis unearthed potential gaps and under-researched areas, such as limited studies on COVID-19 metaphor even though the outbreak had started at the end of 2019. Future studies on this research could include more specialized corpora, specifically in the under-researched topics, to fill in the gaps in this area of study.
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/mf47g/" target="_blank">Corpus-based Studies of Metaphor: An Overview</a>
|
||
</div></li>
|
||
<li><strong>The Landscape of Neutralizing antibodies (NAb): Production, Mechanisms of Action (MOA), FDA approved-antibodies, and Functional assay</strong> -
|
||
<div>
|
||
A neutralizing antibody (NAb) is an antibody that is responsible for defending cells from pathogens, which are organisms that cause disease. They are made by B-cells in the bone marrow, and their production is triggered by both infections and vaccinations against infections. Regarding neutralizing antibody activity, Neutralization can be achieved through four main mechanisms, which are summarized in this article. FDA has approved many neutralizing antibodies (NAb), and GeneMedi provides the corresponding antibodies targeting Pathogens including SARS-CoV-2, Human Immunodeficiency Virus (HIV), and Hepatitis B virus (HBV), Rabies virus, Respiratory syncytial virus (RSV), and so on. This article described the Production, Mechanisms of Action (MOA), FDA approved-antibodies, and Functional assay of Neutralizing antibodies (NAb).
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://osf.io/axuc2/" target="_blank">The Landscape of Neutralizing antibodies (NAb): Production, Mechanisms of Action (MOA), FDA approved-antibodies, and Functional assay</a>
|
||
</div></li>
|
||
<li><strong>Identification of a Papain-Like Protease Inhibitor with Potential for Repurposing in Combination with an Mpro Protease Inhibitor for Treatment of SARS-CoV-2</strong> -
|
||
<div>
|
||
SARS-CoV-2 requires two cysteine proteases for viral polypeptide processing to allow maturation and replication: the 3Clike protease also known as the Main protease (Mpro) and the papain-like protease (PLpro). In addition to its critical role in viral replication, PLpro removes post-translational modifications like ubiquitin and interferon-stimulated gene product 15 (ISG15) from host proteins through its deubiquitinase domain, leading to host immunosuppression and increased ability of the virus to evade the host antiviral immune response. Through screening of a custom clinical compound library, we identified eltrombopag (DDL701), a thrombopoietin receptor antagonist, as having PLpro inhibitory activity that is sustained in the presence of the Mpro inhibitor nirmatrelvir. DDL701 also suppressed both the deubiquitinase and ISG15 cleavage activities of PLpro. In addition, DDL701 partially restored interferon-{beta} induction, an element of the host immune response, in an in vitro model system. Further, modeling and docking studies suggest DDL701 interacts with the active site region of the PLpro enzyme and pilot pharmacokinetic studies indicate it is brain permeable. DDL701 is already approved for treatment of thrombocytopenia and has previously been shown to achieve human plasma levels after oral dosing that is above the IC50 needed for it to exert its PLpro inhibitory activity in vivo. In addition, it has also been reported to have antiviral efficacy against SARS-CoV-2. DDL-701 thus represents a drug that can immediately be repurposed and undergo clinical evaluation as a PLpro inhibitor that may be most effectively used in a protease inhibitor cocktail with an Mpro inhibitor such as nirmatrelvir (Paxlovid) for the treatment of COVID19.
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.18.500363v1" target="_blank">Identification of a Papain-Like Protease Inhibitor with Potential for Repurposing in Combination with an Mpro Protease Inhibitor for Treatment of SARS-CoV-2</a>
|
||
</div></li>
|
||
<li><strong>In silico repurposed drugs against monkeypox virus</strong> -
|
||
<div>
|
||
Monkeypox is an emerging epidemic of concern. The disease is caused by the monkeypox virus and an increasing global incidence with a 2022 outbreak that has spread to Europe amid the COVID-19 pandemic. The new outbreak is associated with novel, previously undiscovered mutations and variants. Currently the US Food and Drug Administration (FDA) approved poxvirus treatment involves use of tecovirimat. However, there is limited pharmacopoeia otherwise, and limited research interest in monkeypox. In this study, virtual screening and molecular dynamics were employed to explore the potential repurposing of multiple drugs previously approved by the FDA or other jurisdictions for other applications. Several drugs are predicted to tightly bind to viral proteins which are crucial in viral replication, including molecules which show high potential for binding the monkeypox D13L capsid protein, whose inhibition has previously been demonstrated to suppress viral replication.
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.17.500371v1" target="_blank">In silico repurposed drugs against monkeypox virus</a>
|
||
</div></li>
|
||
<li><strong>Ad26.COV2.S priming provides a solid immunological base for mRNA-based COVID-19 booster vaccination</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
A large proportion of the global population received a single dose of the Ad26.COV2.S coronavirus disease-2019 (COVID-19) vaccine as priming vaccination, which was shown to provide protection against moderate to severe COVID-19. However, the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants that harbor immune-evasive mutations in the spike protein led to the recommendation of booster vaccinations after Ad26.COV2.S priming. Recent studies showed that heterologous booster vaccination with an mRNA-based vaccine following Ad26.COV2.S priming leads to high antibody levels. However, how heterologous booster vaccination affects other functional aspects of the immune response remains unknown. Here, we performed immunological profiling on samples obtained from Ad26.COV2.S-vaccinated individuals before and after a homologous (Ad26.COV2.S) or heterologous (mRNA-1273 or BNT162b2) booster vaccination. Both homologous and heterologous booster vaccination increased antibodies with multiple functionalities towards ancestral SARS-CoV-2, the Delta and Omicron BA.1 variants. Especially, mRNA-based booster vaccination induced high levels of neutralizing antibodies and antibodies with various Fc-mediated effector functions such as antibody-dependent cellular cytotoxicity and phagocytosis. In contrast, T cell responses were similar in magnitude following homologous or heterologous booster vaccination, and retained functionality towards Delta and Omicron BA.1. However, only heterologous booster vaccination with an mRNA-based vaccine led to the expansion of SARS-CoV-2-specific T cell clones, without an increase in the breadth of the T cell repertoire as assessed by T cell receptor sequencing. In conclusion, we show that Ad26.COV2.S priming vaccination provides a solid immunological base for heterologous boosting with an mRNA-based COVID-19 vaccine, increasing humoral and cellular responses targeting newly emerging variants of concern.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.15.22277639v1" target="_blank">Ad26.COV2.S priming provides a solid immunological base for mRNA-based COVID-19 booster vaccination</a>
|
||
</div></li>
|
||
<li><strong>Loss of SARS-CoV-2 Seropositivity among Healthy Young Adults over Seven Months</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
Objective: We conducted a longitudinal study to estimate immunity produced in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among university students over seven months. Methods: All participants were attending a public university and resided in Pitt County, North Carolina. University students enrolled weekly for 10 weeks between August 26, 2020 and October 28, 2020, resulting in 136 young adults completing at least one study visit by November 17, 2020. Enrolled students completed an online survey and nasal swab collection at two week intervals and monthly blood collection between August 26, 2020 and March 31, 2021. Results: Amongst 695 serum samples tested during follow-up, the prevalence of a positive result for anti-nucleocapsid antibodies (N-IgG) was 9.78%. In 22 students with more than one positive N-IgG serum sample, 68.1% of group had decline of N-IgG below positive threshold over 140 days. Anti-spike antibodies were detected in all 11 vaccinated students who were vaccinated during March 2021. Conclusions: In healthy young adults, N-IgG wanes below detectable threshold within five months. S-IgG remained consistently elevated months after infection, and significantly increased after vaccination.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.15.22277688v1" target="_blank">Loss of SARS-CoV-2 Seropositivity among Healthy Young Adults over Seven Months</a>
|
||
</div></li>
|
||
<li><strong>Model training periods impact estimation of COVID-19 incidence from wastewater viral loads</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
<b>Background:</b> Wastewater-based epidemiology (WBE) has been deployed broadly as an early warning tool for emerging COVID-19 outbreaks. WBE can inform targeted interventions and identify communities with high transmission, enabling quick and effective response. As wastewater becomes an increasingly important indicator for COVID-19 transmission, more robust methods and metrics are needed to guide public health decision making. <b>Objectives:</b> The aim of this research was to develop and implement a mathematical framework to infer incident cases of COVID-19 from SARS-CoV-2 levels measured in wastewater. We propose a classification scheme to assess the adequacy of model training periods based on clinical testing and assess the sensitivity of model predictions to training periods. <b>Methods:</b> We present a Bayesian deconvolution method and linear regression to estimate COVID-19 cases from wastewater data. We described an approach to characterize adequacy in testing during specific time periods and provided evidence to highlight the importance of model training periods on the projection of cases. We estimated the effective reproductive number (<i>Re</i>) directly from observed cases and from the reconstructed incidence of cases from wastewater. The proposed modeling framework was applied to three Northern California communities served by distinct wastewater treatment plants. <b>Results:</b> Both deconvolution and linear regression models consistently projected robust estimates of prevalent cases and <i>Re</i> from wastewater influent samples when assuming training periods with adequate testing. Case estimates from models that used poorer-quality training periods consistently underestimated observed cases. <b>Discussion:</b> Wastewater surveillance data requires robust statistical modeling methods to provide actionable insight for public health decision-making. We propose and validate a modeling framework that can provide estimates of prevalent COVID-19 cases and <i>Re</i> from wastewater data that can be used as tool for disease surveillance including quality assessment for potential training data.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.16.22276772v1" target="_blank">Model training periods impact estimation of COVID-19 incidence from wastewater viral loads</a>
|
||
</div></li>
|
||
<li><strong>The association of typical and atypical symptoms on in-hospital mortality of older adults with COVID-19: a multicentre cohort study</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
Atypical disease presentations are common in older adults with COVID-19. The objective of this study was to determine the prevalence of atypical and typical symptoms in older adults with COVID-19 through progressive pandemic waves and the association of these symptoms with in-hospital mortality. This retrospective cohort study included consecutive adults aged over 65 years with confirmed COVID-19 infection who were admitted to seven hospitals in Toronto, Canada from March 1, 2020 to June 30, 2021. The median age for the 1786 patients was 78.0 years and 847 (47.5%) were female. Atypical symptoms (as defined by geriatric syndromes) occurred in 1187 patients (66.5%), but rarely occurred in the absence of other symptoms (n=106, 6.2%). The most common atypical symptoms were anorexia (n=598, 33.5%), weakness (n=519, 23.9%), and delirium (n=449, 25.1%). Dyspnea (adjusted odds ratio [aOR] 2.05, 95% confidence interval [CI] 1.62-2.62), tachycardia (aOR 1.87, 95% CI 1.14-3.04), and delirium (aOR 1.52, 95% CI 1.18-1.96) were independently associated with in-hospital mortality. In a cohort of older adults hospitalized with COVID-19 infection, atypical presentations frequently overlapped with typical symptoms. Further research should be directed at understanding the cause and clinical significance of atypical presentations in older adults.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.16.22277716v1" target="_blank">The association of typical and atypical symptoms on in-hospital mortality of older adults with COVID-19: a multicentre cohort study</a>
|
||
</div></li>
|
||
<li><strong>Slow waning of antibodies following a third dose of BNT162b2 in adults who had previously received two doses of inactivated vaccine</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
Introduction: Third doses of COVID-19 vaccination provide an important boost to immunity, reducing the risk of symptomatic infection and the risk of severe disease. Third doses have been particularly important for improving protection against variants. However, waning of clinical protection particularly against Omicron has been noted after receipt of third doses. Methods: We administered BNT162b2 as a third dose to adults aged ≥30 years who had previously received two doses of inactivated vaccination. We collected blood before the third dose and again after one month and six months, and tested sera using a spike receptor binding domain IgG enzyme-linked immunosorbent assay, a surrogate virus neutralization test, and live virus plaque reduction neutralization assay against ancestral virus and Omicron BA.2. Results: We administered BNT162b2 as a third dose to 314 adults. We found robust antibody responses to the ancestral strain at six months after receipt of BNT162b2. Antibody responses to Omicron BA.2 were weaker after the third dose and had declined to a low level by six months. From a small number of participants we observed that natural infection or a fourth dose of vaccination generated similar antibody levels against ancestral virus, but infection generated higher antibody level against Omicron BA.2 than vaccination, suggesting a potential advantage in the breadth of antibody response from hybrid immunity. Conclusions: While antibody levels against the ancestral strain remained robust at six months after the third dose, antibody levels against Omicron BA.2 had fallen to low levels suggesting the potential benefits of a fourth dose.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.18.22277741v1" target="_blank">Slow waning of antibodies following a third dose of BNT162b2 in adults who had previously received two doses of inactivated vaccine</a>
|
||
</div></li>
|
||
<li><strong>Exploring Impacts to COVID-19 Herd Immunity Thresholds Under Demographic Heterogeneity that Lowers Vaccine Effectiveness</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
The COVID-19 pandemic has caused severe health, economic, and societal impacts across the globe. Although highly efficacious vaccines were developed at an unprecedented rate, the heterogeneity in vaccinated populations has reduced the ability to achieve herd immunity. Specifically, as of Spring 2022, the 0-4 year-old population is still unable to be vaccinated and vaccination rates across 5-11 year olds are low. Additionally, vaccine hesitancy for older populations has further stalled efforts to reach herd immunity thresholds. This heterogeneous vaccine landscape increases the challenge of anticipating disease spread in a population. We developed an age-structured Susceptible-Infectious-Recovered-type mathematical model to investigate the impacts of unvaccinated subpopulations on herd immunity. The model considers two types of undervaccination: age-related and behavior-related, by incorporating four age groups based on available FDA-approved vaccines. The model accounts for two different types of vaccines, mRNA (e.g., Pfizer, Moderna) and vector (e.g., Johnson and Johnson), as well as their effectiveness. Our goal is to analyze different scenarios to quantify which subpopulations and vaccine characteristics (e.g., rate or efficacy) most impact infection levels in the United States, using the state of New Mexico as an example.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.18.22277763v1" target="_blank">Exploring Impacts to COVID-19 Herd Immunity Thresholds Under Demographic Heterogeneity that Lowers Vaccine Effectiveness</a>
|
||
</div></li>
|
||
<li><strong>A pilot surveillance report of SARS-CoV-2 rapid antigen test results among volunteers in Germany, 1st week of July 2022</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
We hypothesized that reported SARS-CoV-2 infection numbers are underestimated and piloted a point prevalence by rapid antigen testing in the VACCELERATE volunteer registry. Between July-1 and July-7, 2022, 7/419 (1.67%) tests were positive. Compared to reports of the German Federal Government, our results suggest a 2.39-fold higher prevalence. Our findings imply that the actual prevalence of SARS-CoV-2 may be higher than detected by current surveillance systems, so that current pandemic surveillance and testing strategies need to be adapted.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.18.22277744v1" target="_blank">A pilot surveillance report of SARS-CoV-2 rapid antigen test results among volunteers in Germany, 1st week of July 2022</a>
|
||
</div></li>
|
||
<li><strong>COVID-19 vaccine effectiveness against progression to in-hospital mortality — Zambia, 2021-2022</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
Background: COVID-19 vaccines are highly effective for reducing severe disease and mortality. However, vaccine effectiveness data is limited from sub-Saharan Africa, where SARS-CoV-2 epidemiology has differed from other regions. We report COVID-19 vaccine effectiveness against progression to in-hospital mortality in Zambia. Methods: We conducted a retrospective cohort study among admitted patients at eight COVID-19 treatment centers across Zambia during April 2021 through March 2022. Patient demographic and clinical information including vaccination status and in-patient disposition (discharged or died) were collected. Multivariable logistic regression was used to assess the odds of in-hospital mortality by vaccination status, adjusted for age, sex, number of comorbid conditions, disease severity, and COVID-19 treatment center. Vaccine effectiveness was calculated from the adjusted odds ratio. Results: Among 1,653 patients with data on their vaccination status and hospitalization outcome, 365 (22.1%) died. For patients who had received ≥1 vaccine dose before hospital admission, 22 (9.3%) died compared with 343 (24.2%) among unvaccinated patients (p <0.01). The median time since receipt of a first vaccine dose was 52.5 days (IQR: 28-107). Vaccine effectiveness for progression to in-hospital mortality among hospitalized patients was 64.8% (95% CI: 42.3-79.4%). Conclusions: Among patients admitted to COVID-19 treatment centers in Zambia, those who were vaccinated had lower odds of in-hospital mortality compared to those who were unvaccinated. These data are consistent with evidence from other countries demonstrating benefit of COVID-19 vaccination. Vaccination is a critical tool for reducing the consequences of COVID-19 in Zambia.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.18.22277749v1" target="_blank">COVID-19 vaccine effectiveness against progression to in-hospital mortality — Zambia, 2021-2022</a>
|
||
</div></li>
|
||
<li><strong>A simple SEIR-V model to estimate COVID-19 prevalence and predict SARS-CoV-2 transmission using wastewater-based surveillance data</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
Wastewater-based surveillance (WBS) has been widely used as a public health tool to monitor SARS-CoV-2 transmission. However, epidemiological inference from WBS data remains understudied and limits its application. In this study, we have established a quantitative framework to estimate COVID-19 prevalence and predict SARS-CoV-2 transmission through integrating WBS data into an SEIR-V model. We conceptually divide the individual-level viral shedding course into exposed, infectious, and recovery phases as an analogy to the compartments in population-level SEIR model. We demonstrated that the temperature effect on viral losses in the sewer can be straightforwardly incorporated in our framework. Using WBS data from the second wave of the pandemic (Oct 02, 2020-Jan 25, 2021) in the Great Boston area, we showed that the SEIR-V model successfully recapitulates the temporal dynamics of viral load in wastewater and predicts the true number of cases peaked earlier and higher than the number of reported cases by 16 days and 8.6 folds (R=0.93), respectively. This work showcases a simple, yet effective method to bridge WBS and quantitative epidemiological modeling to estimate the prevalence and transmission of SARS-CoV-2 in the sewershed, which could facilitate the application of wastewater surveillance of infectious diseases for epidemiological inference and inform public health actions.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.17.22277721v1" target="_blank">A simple SEIR-V model to estimate COVID-19 prevalence and predict SARS-CoV-2 transmission using wastewater-based surveillance data</a>
|
||
</div></li>
|
||
<li><strong>Pandemic modelling for regions implementing an elimination strategy</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
During the COVID-19 pandemic, some countries, such as Australia, China, Iceland, New Zealand, Thailand and Vietnam, successfully implemented an elimination strategy. Until June 2021, Atlantic Canada and Canada9s territories had also experienced prolonged periods with few SARS-CoV-2 community cases. Such regions had a need for epidemiological models that could assess the risk of SARS-CoV-2 outbreaks, but most existing frameworks are applicable to regions where SARS-CoV-2 is spreading in the community, and so it was necessary to adapt existing frameworks to meet this need. We distinguish between infections that are travel-related and those that occur in the community, and find that in Newfoundland and Labrador (NL), Nova Scotia, and Prince Edward Island the mean percentage of daily cases that were travel-related was 80% or greater (July 1, 2020 – May 31, 2021). We show that by December 24, 2021, the daily probability of an Omicron variant community outbreak establishing in NL was near one, and nearly twice as high as the previous high, which occurred in September 2021 when the Delta variant was dominant. We evaluate how vaccination and new variants might affect hypothetical future outbreaks in Mt. Pearl, NL. Our modelling framework can be used to evaluate alternative plans to relax public health restrictions when high levels of vaccination are achieved in regions that have implemented an elimination strategy.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.18.22277695v1" target="_blank">Pandemic modelling for regions implementing an elimination strategy</a>
|
||
</div></li>
|
||
<li><strong>COVID-19 Vaccine Booster Dose Willingness Among Patients with Inflammatory Bowel Disease on Infliximab and Vedolizumab: A Cross-Sectional Study</strong> -
|
||
<div>
|
||
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
||
Background: Vaccination has been effective in preventing COVID-19 infections and related mortality. However, waning immunity after the two-dose vaccination prompted health authorities to recommend a third dose of COVID-19 vaccine to boost immunity. The aim of our study was to assess willingness to receive a third (booster) dose among patients with IBD. Methods: A cross-sectional study was performed at a tertiary care inflammatory bowel disease center. Patients were recruited at the infusion room from January 1st, 2022, until March 31st, 2022. The primary outcome was the prevalence of BNT162b2 third (booster) dose in infliximab or vedolizumab treated patients with IBD. The secondary outcome evaluated whether the prevalence of BNT162b2 third (booster) dose differed based on type of COVID-19 vaccine, gender, age, type of biologic therapy and citizenship. Results: In total, 499 patients with IBD were included in this study. The median age was 34.5 years, and 60% had ulcerative colitis (UC). Among the study participants, 302 (60.5%) patients were vaccinated with BNT162b2, and 197 (39.5%) were vaccinated with ChAdOx1 nCoV-19. Of the total number of participants, 400 (80.2%) were receiving infliximab, and 99 (19.8%) were receiving vedolizumab. Overall, 290 (58.1%) of the included patients were willing to receive the third (booster) dose. Patients vaccinated with BNT162b2 were more likely to receive booster dose compared to patients vaccinated with ChAdOx1 nCoV-19 [201 (66.5%) vs 101 (33.5%), p = 0.014]. Infliximab-treated patients were more likely to receive booster dose compared to patients receiving vedolizumab [310 (77.5%) vs 62 (62.6%), p = 0.002]. There was no statistical difference in willingness to receive booster dose in terms of age, nationality, or gender. Conclusion: The percentage of patients with IBD willing or have received a third (booster) dose of BNT162b2 vaccine was lower compared to general population. In addition, patients who received two doses of BNT162b2 vaccines were more likely to receive a third (booster) dose compared to patients who received ChAdOx1 nCoV-19. Patients treated with infliximab were more likely to receive a third (booster) dose of COVID-19 vaccine.
|
||
</p>
|
||
</div>
|
||
<div class="article-link article-html-link">
|
||
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.18.22277757v1" target="_blank">COVID-19 Vaccine Booster Dose Willingness Among Patients with Inflammatory Bowel Disease on Infliximab and Vedolizumab: A Cross-Sectional Study</a>
|
||
</div></li>
|
||
</ul>
|
||
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
|
||
<ul>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bank of Human Leukocytes From COVID-19 Convalescent Donors With an Anti-SARS-CoV-2 Cellular Immunity</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Generation of a biobank allowing the cryopreservation of leucocytes from COVID19 convalescent donors<br/><b>Sponsor</b>: Central Hospital, Nancy, France<br/><b>Not yet recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Generation of SARS-CoV-2-specific T Lymphocytes From Recovered Donors and Administration to High-risk COVID-19 Patients</strong> - <b>Condition</b>: Severe COVID-19<br/><b>Interventions</b>: Biological: Coronavirus-2-specific T cells; Other: standard of care (SOC)<br/><b>Sponsors</b>: George Papanicolaou Hospital; General Hospital Of Thessaloniki Ippokratio<br/><b>Recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Randomised, Multi-centre, Double-blind, Phase 3 Study to Observe the Effectiveness, Safety and Tolerability of Molnupiravir Compared to Placebo Administered Orally to High-risk Adult Outpatients With Mild COVID-19 Receiving Local Standard of Care in South Africa</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Molnupiravir 200 mg<br/><b>Sponsors</b>: University of Witwatersrand, South Africa; Bill and Melinda Gates Foundation<br/><b>Not yet recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluate the Efficacy and Safety of FB2001 in Hospitalized Patients With Moderate to Severe COVID-19 (BRIGHT Study)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: FB2001; Drug: FB2001 placebo<br/><b>Sponsor</b>: Frontier Biotechnologies Inc.<br/><b>Not yet recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Engaging Staff to Improve COVID-19 Vaccination Response at Long-Term Care Facilities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Full Intervention; Other: Enhanced Usual Care<br/><b>Sponsors</b>: Kaiser Permanente; Patient-Centered Outcomes Research Institute; Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)<br/><b>Recruiting</b></p></li>
|
||
<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 to Evaluate the Efficacy of PanCytoVir™ for the Treatment of Non-Hospitalized Patients With COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: PanCytoVir™ (probenecid); Drug: Placebo<br/><b>Sponsor</b>: TrippBio, Inc.<br/><b>Not yet recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Value of Montelukast as a Potential Treatment of Post COVID-19 Persistent Cough</strong> - <b>Condition</b>: Post COVID-19<br/><b>Intervention</b>: Drug: Montelukast Sodium Tablets<br/><b>Sponsor</b>: Assiut University<br/><b>Completed</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Topical Antibacterial Agents for Prevention of COVID-19</strong> - <b>Conditions</b>: COVID-19; SARS-CoV2 Infection<br/><b>Interventions</b>: Drug: Neosporin; Other: Vaseline<br/><b>Sponsors</b>: Yale University; Bill and Melinda Gates Foundation<br/><b>Not yet recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">**NanoMn®_COVID-19 A Prospective, Multicenter, Randomized, Placebo-controlled, Parallel-group, Double-blind Trial to Evaluate the Clinical Efficacy of NanoManganese® on Top of Standard of Care, in Adult Patients With Moderate to Severe Coronavirus Disease 2019 (COVID-19)** - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Drug: Placebo; Drug: Experimental drug<br/><b>Sponsor</b>: Medesis Pharma SA<br/><b>Recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study</strong> - <b>Condition</b>: Post-COVID19 Condition<br/><b>Interventions</b>: Combination Product: Plasma Exchange Procedure; Other: Sham Plasma Exchange Procedure<br/><b>Sponsors</b>: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; IrsiCaixa; Banc de Sang i Teixits<br/><b>Not yet recruiting</b></p></li>
|
||
<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 Effectiveness of Proprietary Rehabilitation Program in Patients After COVID-19 Infection</strong> - <b>Conditions</b>: COVID-19; Rehabilitation<br/><b>Interventions</b>: Other: Respiratory training with the use of resistance set on respiratory muscle trainer; Other: Respiratory training without resistance set on respiratory muscle trainer<br/><b>Sponsor</b>: Medical University of Bialystok<br/><b>Recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Developing an Integrative, Recovery-Based, Post-Acute COVID-19 Syndrome (PACS) Psychotherapeutic Intervention</strong> - <b>Condition</b>: Post-acute COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: PACS Coping and Recovery (PACS-CR) Intervention<br/><b>Sponsor</b>: VA Office of Research and Development<br/><b>Not yet recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mineralocorticoid Use in COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; ARDS<br/><b>Intervention</b>: Drug: Fludrocortisone Acetate 0.1 MG<br/><b>Sponsor</b>: Ain Shams University<br/><b>Completed</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Dose Escalation Phase 1 Study Evaluating the Safety and Pharmacokinetics of an Inhaled COVID-19 Inhibitor Delcetravir in Healthy Subjects</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Combination Product: Delcetravir dry powder inhaler<br/><b>Sponsor</b>: Esfam Biotech Pty Ltd<br/><b>Not yet recruiting</b></p></li>
|
||
<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 to Evaluate the Safety and Immunogenicity of Ad5-vector Based Vaccine Against Coronavirus Variants in Adults (≥18 Years) Immunized With 2 Doses of mRNA Vaccines Plus One Dose of Booster AZD1222 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Bivalent Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector); Biological: Bivalent Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) for Inhalation; Biological: mRNA-based COVID-19 vaccine<br/><b>Sponsor</b>: CanSino Biologics Inc.<br/><b>Not yet recruiting</b></p></li>
|
||
</ul>
|
||
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
|
||
<ul>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In vitro evolution predicts emerging SARS-CoV-2 mutations with high affinity for ACE2 and cross-species binding</strong> - Emerging SARS-CoV-2 variants are creating major challenges in the ongoing COVID-19 pandemic. Being able to predict mutations that could arise in SARS-CoV-2 leading to increased transmissibility or immune evasion would be extremely valuable in development of broad-acting therapeutics and vaccines, and prioritising viral monitoring and containment. Here we use in vitro evolution to seek mutations in SARS-CoV-2 receptor binding domain (RBD) that would substantially increase binding to ACE2. We find…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Drug repurposing based on a quantum-inspired method versus classical fingerprinting uncovers potential antivirals against SARS-CoV-2</strong> - The COVID-19 pandemic has accelerated the need to identify new antiviral therapeutics at pace, including through drug repurposing. We employed a Quadratic Unbounded Binary Optimization (QUBO) model, to search for compounds similar to Remdesivir, the first antiviral against SARS-CoV-2 approved for human use, using a quantum-inspired device. We modelled Remdesivir and compounds present in the DrugBank database as graphs, established the optimal parameters in our algorithm and resolved the Maximum…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cap-independent translation and a precisely located RNA sequence enable SARS-CoV-2 to control host translation and escape anti-viral response</strong> - Translation of SARS-CoV-2-encoded mRNAs by the host ribosomes is essential for its propagation. Following infection, the early expressed viral protein NSP1 binds the ribosome, represses translation, and induces mRNA degradation, while the host elicits an anti-viral response. The mechanisms enabling viral mRNAs to escape this multifaceted repression remain obscure. Here we show that expression of NSP1 leads to destabilization of multi-exon cellular mRNAs, while intron-less transcripts, such as…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Iron and iron-related proteins in COVID-19</strong> - COVID-19 can cause detrimental effects on health. Vaccines have helped in reducing disease severity and transmission but their long-term effects on health and effectiveness against future viral variants remain unknown. COVID-19 pathogenesis involves alteration in iron homeostasis. Thus, a contextual understanding of iron-related parameters would be very valuable for disease prognosis and therapeutics.Accordingly, we reviewed the status of iron and iron-related proteins in COVID-19….</p></li>
|
||
<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 apigenin-based biflavonoid derivatives as potential therapeutic agents against viral protease (3CLpro) of SARS-CoV-2 via molecular docking, molecular dynamics and quantum mechanics studies</strong> - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic COVID-19 disease that affects human respiratory function. Despite the scientific progression made in the development of the vaccine, there is an urgent need for the discovery of antiviral drugs for better performance at different stages of SARS-CoV-2 reproduction. The main protease (Mpro or 3CLpro) plays a pivotal role in the life cycle of the virus, making it an attractive target for the…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Variations of SARS-CoV-2 in the Iranian population and candidate putative drug-like compounds to inhibit the mutated proteins</strong> - The first cases of the novel coronavirus, SARS-CoV-2, were detected in December 2019 in Wuhan, China. Nucleotide substitutions and mutations in the SARS-CoV-2 sequence can result in the evolution of the virus and its rapid spread across the world. Therefore, understanding genetic variants of SARS-CoV-2 and targeting the conserved elements responsible for viral replication have great benefits for detecting its infection sources and diagnosing and treating COVID-19. In this study, we used the…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Synthesis, spectral characterization, crystal structure and computational investigation of 2-formyl-6-methoxy-3-carbethoxy quinoline as potential SARS-CoV inhibitor</strong> - The recent COVID-19 outbreak caused by the novel coronavirus SARS-CoV-2 has an immense impact on global health and economy. Although vaccines are being used, urgent need of drugs based on natural products with high efficacy and safety is a pressing priority. Quinoline alkaloids are well known for their therapeutic action against malaria; initially, it was tried against Coronaviruses. It is a basic vital scaffold to design drugs with required biological and pharmacological activities. In this…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Anti-Histamine Azelastine, Identified by Computational Drug Repurposing, Inhibits Infection by Major Variants of SARS-CoV-2 in Cell Cultures and Reconstituted Human Nasal Tissue</strong> - Background and purpose: The COVID-19 pandemic continues to pose challenges, especially with the emergence of new SARS-CoV-2 variants that are associated with higher infectivity and/or compromised protection afforded by the current vaccines. There is a high demand for additional preventive and therapeutic strategies effective against this changing virus. Repurposing of approved or clinically tested drugs can provide an immediate solution. Experimental Approach: We applied a novel computational…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Discovery of TCMs and derivatives against the main protease of SARS-CoV-2 via high throughput screening, ADMET analysis, and inhibition assay in vitro</strong> - The rapidly evolving Coronavirus Disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide with thousands of deaths and infected cases. For the identification of effective treatments against this disease, the main protease (M^(pro)) of SARS‑CoV‑2 was found to be an attractive drug target, as it played a central role in viral replication and transcription. Here, we report the results of high-throughput molecular docking with…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Carlina oxide inhibits the interaction of SARS-CoV-2 S glycoprotein with angiotensin-converting enzyme 2</strong> - Carlina acaulis plant is a potential target for the industrial production of phytochemicals that display applicability in pharmacy and medicine. The dry roots of C. acaulis contain up to 2 % of essential oil, the main component (up to 99 %) of which is carlina oxide [2-(3-phenylprop-1-ynyl)furan]. This compound shows multidirectional biological activity, including antibacterial and antifungal properties. Here, we evaluated the capacity of carlina oxide to inhibit the interaction between…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Protein-protein conjugation enhances immunogenicity of SARS-CoV-2 Receptor Binding Domain (RBD) vaccines</strong> - Several effective SARS-CoV-2 vaccines have been developed using different technologies. Although these vaccines target the isolates collected early in the pandemic, many have protected against serious illness from newer variants. Nevertheless, efficacy has diminished against successive variants and the need for effective and affordable vaccines persists especially in the developing world. Here, we adapted our protein-protein conjugate vaccine technology to generate a vaccine based on receptor…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Conserved 3’ UTR of Severe Acute Respiratory Syndrome Coronavirus 2: Potential Therapeutic Targets</strong> - Our previous paper showed that microRNAs (miRNAs) present within human placental or mesenchymal stem cell-derived extracellular vesicles (EVs) directly interacted with the RNA genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), inhibiting viral replication. In this paper, we analyzed whether these miRNAs could exert antiviral activity against other variants of SARS-CoV-2. We downloaded compete SARS-CoV-2 genome data submitted to the National Center for Biotechnology…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Paxlovid: Mechanism of Action, Synthesis, and <em>In Silico</em> Study</strong> - In this work, the discovery and description of PF-07321332, a major bioavailable oral SARS-CoV-2 protease inhibitor with in vitro human coronavirus antiviral activity, and excellent selection of off-target and in vivo immune profiles are reported. Various drugs and novel compound candidates for the treatment of the COVID-19 pandemic have been developed. PF-07321332 (or nirmatrelvir) is a new oral antiviral drug developed by Pfizer. In response to the pandemic, Pfizer has developed the COVID…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The SARS-CoV-2 main protease (M<sup>pro</sup>): Structure, function, and emerging therapies for COVID-19</strong> - The main proteases (M^(pro)), also termed 3-chymotrypsin-like proteases (3CL^(pro)), are a class of highly conserved cysteine hydrolases in β-coronaviruses. Increasing evidence has demonstrated that 3CL^(pro)s play an indispensable role in viral replication and have been recognized as key targets for preventing and treating coronavirus-caused infectious diseases, including COVID-19. This review is focused on the structural features and biological function of the severe acute respiratory syndrome…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Lopinavir-menthol co-crystals for enhanced dissolution rate and intestinal absorption</strong> - Lopinavir is an antiretroviral, antiparasitic agent and recently utilized in treatment of COVID-19. Unfortunately, lopinavir exhibited poor oral bioavailability due to poor dissolution, extensive pre-systemic metabolism, and significant P-glycoprotein intestinal efflux. Accordingly, the aim was to enhance dissolution rate and intestinal absorption of lopinavir. This employed co-processing with menthol which is believed to modify crystalline structures and inhibit intestinal efflux. Lopinavir was…</p></li>
|
||
</ul>
|
||
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
|
||
|
||
|
||
<script>AOS.init();</script></body></html> |