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178 lines
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<title>16 July, 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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<ul>
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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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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Oral immunization with rVSV bivalent vaccine elicits protective immune responses, including ADCC, against both SARS-CoV-2 and Influenza A viruses</strong> -
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<div>
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COVID-19 and influenza both cause enormous disease burdens, and vaccines are the primary measures for their control. Since these viral diseases are transmitted through the mucosal surface of the respiratory tract, developing an effective and convenient mucosal vaccine should be a high priority. We previously reported a recombinant vesicular stomatitis virus (rVSV)-based bivalent vaccine (v-EM2/SP{Delta}C1Delta) that protects animals from both SARS-CoV-2 and influenza viruses via intramuscular and intranasal immunization. Here, we further investigated the immune response induced by oral immunization with this vaccine and its protective efficacy in mice. The results demonstrated that the oral cavity delivery, like the intranasal route, elicited strong and protective systemic immune responses against SARS-CoV-2 and influenza A virus. This included high levels of neutralizing antibodies (NAbs) against SARS-CoV-2, as well as strong anti-SARS-CoV-2 spike protein (SP) antibody-dependent cellular cytotoxicity (ADCC) and anti-influenza M2 ADCC responses in mice sera. Furthermore, it provided efficient protection against challenge with influenza H1N1 virus in a mouse model, with a 100% survival rate and a significant low lung viral load of influenza virus. All these findings provide substantial evidence for the effectiveness of oral immunization with the rVSV bivalent vaccine.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.14.549076v1" target="_blank">Oral immunization with rVSV bivalent vaccine elicits protective immune responses, including ADCC, against both SARS-CoV-2 and Influenza A viruses</a>
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</div></li>
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<li><strong>Absence of SARS-CoV-2 in Wildlife of Northeastern Minnesota and Isle Royale National Park</strong> -
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<div>
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We investigated the presence of SARS-CoV-2 in free-ranging wildlife populations in Northeastern Minnesota on the Grand Portage Indian Reservation and Isle Royale National Park. 120 nasal samples were collected from white-tailed deer, moose, gray wolves, and black bears monitored for conservation efforts during 2022-2023. Samples were tested for viral RNA by RT-qPCR using the CDC N1/N2 primer set. Our data indicate that no wildlife samples were positive for SARS-CoV-2 RNA. Continued surveillance is therefore crucial to better understand the changing landscape of zoonotic SARS-CoV-2 in the Upper Midwest.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.14.549077v1" target="_blank">Absence of SARS-CoV-2 in Wildlife of Northeastern Minnesota and Isle Royale National Park</a>
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</div></li>
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<li><strong>Cognitive Adaptations in Career Decision-Making Among Chinese Undergraduates During the COVID-19 Pandemic</strong> -
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The authors of this article use the mindsponge theory to understand better the cognitive dynamics underlying the challenges Chinese undergraduates face in making career decisions during the COVID-19 pandemic.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/s68bz/" target="_blank">Cognitive Adaptations in Career Decision-Making Among Chinese Undergraduates During the COVID-19 Pandemic</a>
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</div></li>
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<li><strong>Methods for Improving Participation Rates in National Self-Administered Web/Mail Surveys: Evidence from the United States</strong> -
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In the United States, increasing access to the internet, the increasing costs of large-scale face-to-face data collections, and the general reluctance of the public to participate in intrusive in-person data collections all mean that new approaches to nationally representative surveys are urgently needed. The COVID-19 pandemic accelerated the need for faster, higher-quality alternatives to face-to-face data collection. These trends place a high priority on the evaluation of innovative web-based data collection methods that are convenient for the U.S. public and yield scientific information of high quality. The web mode is particularly appealing because it is relatively inexpensive, it is logistically flexible to implement, and it affords a high level of privacy and confidentiality when correctly implemented. With this study, we aimed to conduct a methodological evaluation of a sequential mixed-mode web/mail data collection protocol, including modular survey design concepts, which was implemented on a national probability sample in the U.S. in 2020-2021. We implemented randomized experiments to test theoretically-informed hypotheses that 1) the use of mail and increased incentives to follow up with households that did not respond to an invitation to complete a household screening questionnaire online would help to recruit different types of households; and 2) the use of modular survey design, which involves splitting a lengthy self-administered survey up into multiple parts that can be completed at a respondent’s convenience, would improve survey completion rates. We find support for the use of mail and increased incentives to follow up with households that have not responded to a web-based screening questionnaire. We did not find support for the use of modular design in this context. Simple descriptive analyses also suggest that attempted telephone reminders may be helpful for the main survey.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/5hxgm/" target="_blank">Methods for Improving Participation Rates in National Self-Administered Web/Mail Surveys: Evidence from the United States</a>
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</div></li>
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<li><strong>Differential laboratory passaging of SARS-CoV-2 viral stocks impacts the in vitro assessment of neutralizing antibodies</strong> -
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<div>
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Viral populations in natural infections can have a high degree of sequence diversity, which can directly impact immune escape. However, antibody potency is often tested in vitro with a relatively clonal viral populations, such as laboratory virus or pseudotyped virus stocks, which may not accurately represent the genetic diversity of circulating viral genotypes. This can affect the validity of viral phenotype assays, such as antibody neutralization assays. To address this issue, we tested whether recombinant virus carrying SARS-CoV-2 spike (VSV-SARS-CoV-2-S) stocks could be made more genetically diverse by passage, and if a stock passaged under selective pressure was more capable of escaping monoclonal antibody (mAb) neutralization than unpassaged stock or than viral stock passaged without selective pressures. We passaged VSV-SARS-CoV-2-S four times concurrently in three cell lines and then six times with or without polyclonal antiserum selection pressure. All three of the monoclonal antibodies tested neutralized the viral population present in the unpassaged stock. The viral inoculum derived from serial passage without antiserum selection pressure was neutralized by two of the three mAbs. However, the viral inoculum derived from serial passage under antiserum selection pressure escaped neutralization by all three mAbs. Deep sequencing revealed the rapid acquisition of multiple mutations associated with antibody escape in the VSV-SARS-CoV-2-S that had been passaged in the presence of antiserum, including key mutations present in currently circulating Omicron subvariants. These data indicate that viral stock that was generated under polyclonal antiserum selection pressure better reflects the natural environment of the circulating virus and may yield more biologically relevant outcomes in phenotypic assays.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.14.549044v1" target="_blank">Differential laboratory passaging of SARS-CoV-2 viral stocks impacts the in vitro assessment of neutralizing antibodies</a>
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</div></li>
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<li><strong>Nanobody repertoire generated against the spike protein of ancestral SARS-CoV-2 remains efficacious against the rapidly evolving virus</strong> -
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<div>
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To date, all major modes of monoclonal antibody therapy targeting SARS-CoV-2 have lost significant efficacy against the latest circulating variants. As SARS-CoV-2 omicron sublineages account for over 90% of COVID-19 infections, evasion of immune responses generated by vaccination or exposure to previous variants poses a significant challenge. A compelling new therapeutic strategy against SARS-CoV-2 is that of single domain antibodies, termed nanobodies, which address certain limitations of monoclonal antibodies. Here we demonstrate that our high-affinity nanobody repertoire, generated against wild-type SARS-CoV-2 spike protein (Mast, Fridy et al. 2021), remains effective against variants of concern, including omicron BA.4/BA.5; a subset is predicted to counter resistance in emerging XBB and BQ.1.1 sublineages. Furthermore, we reveal the synergistic potential of nanobody cocktails in neutralizing emerging variants. Our study highlights the power of nanobody technology as a versatile therapeutic and diagnostic tool to combat rapidly evolving infectious diseases such as SARS-CoV-2.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.14.549041v1" target="_blank">Nanobody repertoire generated against the spike protein of ancestral SARS-CoV-2 remains efficacious against the rapidly evolving virus</a>
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<li><strong>A simulation framework for modeling the within-patient evolutionary dynamics of SARS-CoV-2</strong> -
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<div>
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The global impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to considerable interest in detecting novel beneficial mutations and other genomic changes that may signal the development of variants of concern (VOCs). The ability to accurately detect these changes within individual patient samples is important in enabling early detection of VOCs. Such genomic scans for positive selection are best performed via comparison of empirical data to simulated data wherein evolutionary factors, including mutation and recombination rates, reproductive and infection dynamics, and purifying and background selection, can be carefully accounted for and parameterized. While there has been work to quantify these factors in SARS-CoV-2, they have yet to be integrated into a baseline model describing intra-host evolutionary dynamics. To construct such a baseline model, we develop a simulation framework that enables one to establish expectations for underlying levels and patterns of patient-level variation. By varying eight key parameters, we evaluated 12,096 different model-parameter combinations and compared them to existing empirical data. Of these, 592 models (~5%) were plausible based on the resulting mean expected number of segregating variants. These plausible models shared several commonalities shedding light on intra-host SARS-CoV-2 evolutionary dynamics: severe infection bottlenecks, low levels of reproductive skew, and a distribution of fitness effects skewed towards strongly deleterious mutations. We also describe important areas of model uncertainty and highlight additional sequence data that may help to further refine a baseline model. This study lays the groundwork for the improved analysis of existing and future SARS-CoV-2 within-patient data.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.13.548462v1" target="_blank">A simulation framework for modeling the within-patient evolutionary dynamics of SARS-CoV-2</a>
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</div></li>
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<li><strong>Multivalent Exosome based protein vaccine: a “mix and match” approach to epidemic viruses’ challenges.</strong> -
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Endemic viruses are becoming increasingly the norm, and the development of a rapid and effective vaccine is emergent. Here, we used our StealthX TM exosome platform to express either Influenza H3 (StealthTM X-Hemagglutinin, STX-H3) or SARS-CoV-2 Delta spike (StealthTM X-Spike, STX-S) protein on the surface and facilitate their trafficking to the exosomes. When administered as single product, both STX-H3 and STX-S induced a strong immunization with the production of a potent humoral and cellular immune response in mice. Interestingly, these effects were obtained with administration of nanograms of protein and without adjuvant. Therefore, we tested the possibility of a multivalent vaccine: STX-H3 and STX-S exosomes were formulated together in a "mix and match" approach and the immune response was further evaluated. We showed that our STX-H3+S cocktail vaccine is as effective as the single components administered separately, resulting in a strong antibody and T-cell response. Our data show that our exosome platform has an enormous potential to revolutionize vaccinology by rapidly facilitating antigen presentation, and for therapeutics by enabling cell and tissue specific targeting.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.13.548895v1" target="_blank">Multivalent Exosome based protein vaccine: a “mix and match” approach to epidemic viruses’ challenges.</a>
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<li><strong>Healthcare in England was affected by the COVID-19 pandemic across the pancreatic cancer pathway: a cohort study using OpenSAFELY-TPP</strong> -
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Background Healthcare across all sectors, in the UK and globally, was negatively affected by the COVID-19 pandemic. We analysed healthcare services delivered to people with pancreatic cancer from January 2015 to March 2023 to investigate the effect of the COVID-19 pandemic. Methods With the approval of NHS England, and drawing from a nationally representative OpenSAFELY-TPP dataset of 24 million patients (over 40% of the English population), we undertook a cohort study of people diagnosed with pancreatic cancer. We queried electronic healthcare records for information on the provision of healthcare services across the pancreatic cancer pathway. To estimate the effect of the COVID-19 pandemic, we predicted the rates of healthcare services if the pandemic had not happened. We used generalised linear models (GLM) and the pre-pandemic data from January 2015 to February 2020 to predict rates in March 2020 to March 2023. The 95% confidence intervals of the predicted values were used to estimate the significance of the difference between the predicted and observed rates. Results The rate of pancreatic cancer and diabetes diagnoses in the cohort was not affected by the pandemic. There were 26,840 people diagnosed with pancreatic cancer from January 2015 to March 2023. The mean age at diagnosis was 72 (11 SD), 48% of people were female, 95% were of White ethnicity and 40% were diagnosed with diabetes. We found a reduction in surgical resections by 25% to 28% during the pandemic. In addition, 20%, 10% and 4% fewer people received BMI, HbA1c and liver function tests respectively before they were diagnosed with pancreatic cancer. There was no impact of the pandemic on the number of people making contact with primary care, but the number of contacts increased on average by 1 to 2 per person amongst those who made contact. Reporting of jaundice decreased by 28%, but recovered within twelve months into the pandemic. Emergency department visits, hospital admissions and deaths were not affected. Conclusions The pandemic affected healthcare in England across the pancreatic cancer pathway. Positive lessons could be learnt from the services that were resilient and those that recovered quickly. The reductions in healthcare experienced by people with cancer have the potential to lead to worse outcomes. Current efforts should focus on addressing the unmet needs of people with cancer.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.02.22283026v2" target="_blank">Healthcare in England was affected by the COVID-19 pandemic across the pancreatic cancer pathway: a cohort study using OpenSAFELY-TPP</a>
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<li><strong>Mobilisation towards formal employment in the healthcare system: A qualitative study of community health workers in South Africa</strong> -
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In low and middle-income countries (LMICs), community health workers (CHWs) play a critical role in delivering primary health care (PHC) services to vulnerable populations. In these settings, they often receive low stipends, function with a lack of basic resources and have little bargaining power with which to demand better working conditions. In this article, we examine CHWs’ employment status, their struggle for recognition as health workers, and their activities to establish labour representation in South Africa. Using a case study approach, we studied seven CHW teams located in semi-urban and rural areas of Gauteng and Mpumalanga Provinces, South Africa. We used in-depth interviews, focus group discussions and observations to gather data from CHWs and their representatives, supervisors and PHC facility staff members. The rural and semi-urban sites CHWs were poorly supervised, resourced and received meagre remuneration, their employment outsourced, without employment benefits and protection. The lack of career progression opportunities demotivated the CHWs, particularly those keen to establish a career in health. In the semi-urban sites, CHWs established a task team to represent them that held regular meetings and often used violent and disruptive strategies against clinic, district and provincial management, which often led to tensions and conflicts with facility staff and programme coordinators. After a meeting with the local provincial legislature, the task team joined a labour union (NEHAWU) in order to be able to participate in the local Bargaining Council. Though they were not successful in getting the government to provide permanent employment, the union negotiated an increase in stipend from R2 500 (136 USD) to R3 500 (192 USD). In contrast, in the rural sites, the CHWs were not actively demanding permanent employment due to their employment contracts being partly managed by non-government organisations (NGOs) managements; they were fearful of being recalled from the government programme. After the study ended, during the height of COVID-19 in 2020, when the need for motivated and effective CHWs became much more obvious to decision makers, the semi-urban-based teams received permanent employment with remuneration between R9-11,000 (500-600 USD). The task team and their protests raised awareness of the plight of the CHWs, and joining a formal union enabled them to negotiate a modest salary increase. However, it was the emergency created by the world-wide COVID-19 pandemic that forced decision-makers to acknowledge their reliance on this community-based cadre. Hopefully this recognition, and the associated gains, will not fade as the pandemic recedes.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.11.23292526v1" target="_blank">Mobilisation towards formal employment in the healthcare system: A qualitative study of community health workers in South Africa</a>
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<li><strong>Environmental Surface Monitoring as a Noninvasive Method for SARS-CoV-2 Surveillance in Community Settings: Lessons from a University Campus Study</strong> -
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Environmental testing of high-touch objects is a potential noninvasive approach for monitoring population-level trends of SARS-CoV-2 and other respiratory viruses within a defined setting. We aimed to determine the association between SARS-CoV-2 contamination on high-touch environmental surfaces, community level case incidence, and university student health data. Environmental swabs were collected from January 2022 to November 2022 from high-touch objects and surfaces from five locations on a large university campus in Florida, USA. RT-qPCR was used to detect and quantify viral RNA, and a subset of positive samples was analyzed by viral genome sequencing to identify circulating lineages. During the study period, we detected SARS-CoV-2 viral RNA on 90.7% of 162 tested samples. Levels of environmental viral RNA correlated with trends in community-level activity and case reports from the student health center. A significant positive correlation was observed between the estimated viral gene copy number in environmental samples and the weekly confirmed cases at the university. Viral sequencing data from environmental samples identified lineages contemporaneously circulating in the local community and state based on genomic surveillance data. Further, we detected emerging variants in environmental samples prior to their identification by clinical genomic surveillance. Our results demonstrate the utility of viral monitoring on high-touch environmental surfaces for SARS-CoV-2 surveillance at a community level. In communities with delayed or limited testing facilities, immediate environmental surface testing may considerably inform epidemic dynamics.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.13.23292575v1" target="_blank">Environmental Surface Monitoring as a Noninvasive Method for SARS-CoV-2 Surveillance in Community Settings: Lessons from a University Campus Study</a>
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<li><strong>SWAMPy: Simulating SARS-CoV-2 Wastewater Amplicon Metagenomes with Python</strong> -
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Motivation: Tracking SARS-CoV-2 variants through genomic sequencing has been an important part of the global response to the pandemic. As well as whole-genome sequencing of clinical samples, this surveillance effort has been aided by amplicon sequencing of wastewater samples, which proved effective in real case studies. Because of its relevance to public healthcare decisions, testing and benchmarking wastewater sequencing analysis methods is also crucial, which necessitates a simulator. Although metagenomic simulators exist, none are fit for the purpose of simulating the metagenomes produced through amplicon sequencing of wastewater. Results: Our new simulation tool, SWAMPy (Simulating SARS-CoV-2 Wastewater Amplicon Metagenomes with Python), is intended to provide realistic simulated SARS-CoV-2 wastewater sequencing datasets with which other programs that rely on this type of data can be evaluated and improved. Availability: The code for this project is available at https://github.com/goldman-gp-ebi/SWAMPy. It can be installed on any Unix-based operating system and is available under the GPL-v3 license.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.10.519890v2" target="_blank">SWAMPy: Simulating SARS-CoV-2 Wastewater Amplicon Metagenomes with Python</a>
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<li><strong>The Effect of COVID-19 on Home Advantage in High- and Low-Stake Situations: Evidence from the European National Football Competitions</strong> -
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The Covid-19 pandemic has significantly altered the way sporting events are observed. With the absence or limited presence of spectators in stadiums, the traditional advantage enjoyed by home teams has diminished considerably. This underscores the notion that the support of home fans can often be considered a key factor of the home advantage (HA) phenomenon, wherein teams perform better in front of their own supporters. However, the impact of reduced attendance on games with higher stakes, as opposed to low-stakes friendly matches, remains uncertain. In this study, we investigate the recently concluded European football championship (EURO 20), wherein several teams had the advantage of playing at home in high-stakes games with only one-third of the stadium capacity filled. Firstly, we demonstrate that the Covid-19 restrictions, leading to reduced fan attendance, resulted in a nearly 50% decrease in HA compared to the HA exhibited by the same teams during the qualification stage preceding EURO 20, even after accounting for team strength. Secondly, we show that while low-stakes friendly matches generally exhibit a smaller overall HA compared to high-stakes games, the absence of fans led to a similar reduction in HA during the low-stakes matches. Utilizing the recently developed Home Advantage Mediated (HAM) model (Bilalić et al., 2021, Scientific Reports, 21558), we were able to attribute the reduction in both high- and low-stakes games to poorer team performance, with no significant contribution from referee bias.
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🖺 Full Text HTML: <a href="https://osf.io/d3xat/" target="_blank">The Effect of COVID-19 on Home Advantage in High- and Low-Stake Situations: Evidence from the European National Football Competitions</a>
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<li><strong>Death Seasonality, Google Community Mobility Trends, Seropositivity Rates, Comparisons of SINADEF Data with WHO Summary Data, and other Data Items as Useful in Analysis of Excess Deaths During the COVID-19 Pandemic in Peru, 2020-2021</strong> -
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The government of Peru carried out extensive tracking of data for deaths and other public health parameters that allow analysis of potential efficacy of interventions used during the early years of the COVID-19 pandemic. Data from those sources for death seasonality, mobility trends, household composition and seropositivity rates, as well as Google community mobility trends, are provided here as can facilitate such analysis. Also, excess deaths as calculated from Peru’s National Death Information System (SINADEF) are compared with monthy summary data for excess deaths for the period 2020-2021 as reported by the World Health Organization.
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🖺 Full Text HTML: <a href="https://osf.io/a9ex5/" target="_blank">Death Seasonality, Google Community Mobility Trends, Seropositivity Rates, Comparisons of SINADEF Data with WHO Summary Data, and other Data Items as Useful in Analysis of Excess Deaths During the COVID-19 Pandemic in Peru, 2020-2021</a>
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<li><strong>Performance of amplicon and capture based next-generation sequencing approaches for the epidemiological surveillance of Omicron SARS-CoV-2 and other variants of concern.</strong> -
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To control the SARS-CoV-2 pandemic, healthcare systems have focused on ramping up their capacity for epidemiological surveillance through viral whole genome sequencing. In this paper, we tested the performance of two protocols of SARS-CoV-2 nucleic acid enrichment, an amplicon enrichment using different versions of the ARTIC primer panel and a hybrid-capture method using KAPA RNA Hypercap. We focused on the challenge of the Omicron variant sequencing, the advantages of automated library preparation and the influence of the bioinformatic analysis in the final consensus sequence. All 94 samples were sequenced using Illumina iSeq 100 and analysed with two bioinformatic pipelines: a custom-made pipeline and an Illumina-owned pipeline. We were unsuccessful in sequencing six samples using the capture enrichment due to low reads. On the other hand, amplicon dropout and mispriming caused the loss of mutation G21987A and the erroneous addition of mutation T15521A respectively using amplicon enrichment. Overall, we found high sequence agreement regardless of method of enrichment, bioinformatic pipeline or the use of automation for library preparation in eight different SARS-CoV-2 variants. Automation and the use of a simple app for bioinformatic analysis can simplify the genotyping process, making it available for more diagnostic facilities and increasing global vigilance.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.14.549026v1" target="_blank">Performance of amplicon and capture based next-generation sequencing approaches for the epidemiological surveillance of Omicron SARS-CoV-2 and other variants of concern.</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>Homologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: SARS-CoV-2 Subunit Recombinant Protein Vaccine<br/><b>Sponsor</b>: PT Bio Farma<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>Role of Ivermectin and Colchicine in Treatment of COVID-19: Randomized Controlled Clinical Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Ivermectin Tablets; Drug: Colchicine 0.5 MG; Drug: Standared managment<br/><b>Sponsor</b>: Ain Shams 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>A Study to Evaluate the Immunogenicity and Safety of A Recombinant Protein COVID-19 Vaccine as Booster Vaccines</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: SCTV01E-2; Biological: SCTV01E<br/><b>Sponsor</b>: Sinocelltech 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>COVID-19 Vaccine Hesitancy Counseling Intervention for Pharmacists</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Standard implementation webinar and online training; Behavioral: Virtual facilitation<br/><b>Sponsors</b>: University of North Carolina, Chapel Hill; University of Arkansas; University of South Carolina; National Institute on Minority Health and Health Disparities (NIMHD)<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>Developing an Effective Intervention to Address Post-Corona-Virus-Disease-2019 Balance Disorders, Weakness and Muscle Fatigue in Individuals Aged 65+</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: Resistance Training<br/><b>Sponsor</b>: Józef Piłsudski University of Physical Education<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>Multimodal Long Covid19</strong> - <b>Condition</b>: Long COVID-19 Syndrome<br/><b>Intervention</b>: Other: Multimodal intervention in Long Covid19<br/><b>Sponsors</b>: Universidad de Magallanes; Teaching Assistance and Research Center of the University of Magallanes CADI-UMAG; Clinical Hospital Dr. Lautaro Navarro Avaria<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>Immunogenicity and Safety Study of SCB-2023 Vaccine as a Booster in Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: SCB-2023 vaccine (trivalent), a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19; intramuscular injection; Biological: SCB-2019 (monovalent), a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19; intramuscular injection<br/><b>Sponsor</b>: Clover Biopharmaceuticals AUS Pty 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>The Safety and Immunogenicity Following a Heterologous Booster Dose of Recombinant SARS-CoV-2 Vaccine LYB002</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: LYB002V14; Biological: LYB002V14A; Biological: LYB002CA<br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.; Affiliated Hospital of North Sichuan Medical College<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>Treatment of Long COVID (TLC) Feasibility Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Low-dose Naltrexone (LDN); Drug: Cetirizine; Drug: Famotidine; Drug: LDN Placebo; Drug: Cetirizine Placebo; Drug: Famotidine Placebo<br/><b>Sponsors</b>: Emory University; CURE Drug Repurposing Collaboratory (CDRC)<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>Efficiency and Safety of Paxlovid for COVID-19 Patients With Severe Chronic Kidney Disease</strong> - <b>Conditions</b>: COVID-19; Renal Insufficiency, Chronic<br/><b>Intervention</b>: Drug: Nirmatrelvir/ritonavir<br/><b>Sponsor</b>: Chinese PLA General 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 Immunogenicity and Safety Following a Heterologous Booster Dose of Recombinant SARS-CoV-2 Vaccine LYB001</strong> - <b>Conditions</b>: COVID-19; Vaccine Reaction<br/><b>Interventions</b>: Biological: LYB001; Biological: CoronaVac<br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.; Affiliated Hospital of North Sichuan Medical College<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>Safety and Efficacy of Anakinra Treatment for Patients With Post Acute Covid Syndrome</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Interventions</b>: Drug: Placebo; Drug: Anakinra 149 MG/ML Prefilled Syringe [Kineret]<br/><b>Sponsor</b>: Hellenic Institute for the Study of Sepsis<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>Effects of Music Combined With Sports Games on Alleviating Psychological Stress, Anxiety and Mental Energy Among Adolescents During COVID-19 Pandemic in Lanzhou Gansu Province China</strong> - <b>Conditions</b>: Stress; Anxiety and Fear<br/><b>Interventions</b>: Behavioral: Music intervention only; Behavioral: Sports games intervention only; Behavioral: Music and sports games intervention<br/><b>Sponsor</b>: Wu Jiarun<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>A Study to Evaluate the Efficacy, Safety, Tolerability and PK of SNS812 in Mild to Moderate COVID-19 Patients</strong> - <b>Condition</b>: Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (Disorder)<br/><b>Interventions</b>: Drug: MBS-COV; Drug: Placebo<br/><b>Sponsor</b>: Oneness Biotech 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>Efficacy of the Therapy With BRAINMAX® Using fMRI for the Treatment of Patients With Asthenia After COVID-19</strong> - <b>Conditions</b>: Asthenia; COVID-19; Functional MRI; Cognitive Impairment<br/><b>Interventions</b>: Other: Structural and functional MRI; Drug: Ethyl methyl hydroxypyridine succinate + Meldonium; Drug: Placebo<br/><b>Sponsor</b>: Promomed, LLC<br/><b>Completed</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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<ul>
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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>‘Pterocephalodes hookeri-Onosma hookeri’ decoction protects against LPS-induced pulmonary inflammation via inhibiting TLR4/ NF-κB signaling pathway</strong> - CONCLUSION: In summary, the combination therapy of ‘P-O’ exhibited good antioxidant activity and anti-inflammatory activity in vitro, as well as a therapeutic effect against pulmonary inflammation in vivo. These findings provide evidence for the clinical application of ‘P-O’ and offer new approaches for treating pneumonia.</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>Intranasal insulin - effects on the sense of smell</strong> - Intranasal insulin (IN) administration is a promising way to deliver the peptide to the central nervous system (CNS), bypassing the blood-brain-barrier and gastrointestinal absorption inhibition. IN receptors are localized in the olfactory mucosa and the brain, mainly in the olfactory bulb, hypothalamus, hippocampus, amygdala, cerebral cortex, and cerebellum. The pleiotropic mechanism of insulin action is characterized by its anti-inflammatory properties, antithrombotic, vasodilatory, and…</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>SARS-CoV-2 spike protein induces lung endothelial cell dysfunction and thrombo-inflammation depending on the C3a/C3a receptor signalling</strong> - The spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can interact with endothelial cells. However, no studies demonstrated the direct effect of the spike protein subunit 1 (S1) in inducing lung vascular damage and the potential mechanisms contributing to lung injury. Here, we found that S1 injection in mice transgenic for human angiotensin converting enzyme 2 (ACE2) induced early loss of lung endothelial thromboresistance at 3 days, as revealed by thrombomodulin loss…</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>SARS-CoV-2 spike protein receptor-binding domain perturbates intracellular calcium homeostasis and impairs pulmonary vascular endothelial cells</strong> - Exposure to the spike protein or receptor-binding domain (S-RBD) of SARS-CoV-2 significantly influences endothelial cells and induces pulmonary vascular endotheliopathy. In this study, angiotensin-converting enzyme 2 humanized inbred (hACE2 Tg) mice and cultured pulmonary vascular endothelial cells were used to investigate how spike protein/S-RBD impacts pulmonary vascular endothelium. Results show that S-RBD leads to acute-to-prolonged induction of the intracellular free calcium concentration…</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>Immunothrombosis and its underlying biological mechanisms</strong> - The evolutionary conserved link between coagulation and innate immunity is a biological process characterized by the thrombosis formation stimulus of immune cells and specific thrombosis-related molecules. In physiological settings, the relationship between the immune system and thrombosis facilitates the recognition of pathogens and damaged cells and inhibits pathogen proliferation. However, when deregulated, the interplay between hemostasis and innate immunity becomes a pathological process…</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>CHO-produced RBD-Fc subunit vaccines with alternative adjuvants generate immune responses against SARS-CoV-2</strong> - Subunit vaccines feature critical advantages over other vaccine platforms such as stability, price, and minimal adverse effects. To maximize immunological protection of subunit vaccines, adjuvants are considered as main components that are formulated within the subunit vaccine. They can modulate adverse effects and enhance immune outcomes. However, the most suitable formulation providing the best immunological outcomes and safety are still under investigation. In this report, we combined…</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>Determining the clinical and cost-effectiveness of nasal sprays and a physical activity and stress management intervention to reduce respiratory tract infections in primary care: A protocol for the ‘Immune Defence’ randomised controlled trial</strong> - BACKGROUND: Most adults in the UK experience at least one viral respiratory tract infection (RTI) per year. Individuals with comorbidities and those with recurrent RTIs are at higher risk of infections. This can lead to more severe illness, worse quality of life and more days off work. There is promising evidence that using common nasal sprays or improving immune function through increasing physical activity and managing stress, may reduce the incidence and severity of RTIs.</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>In</em><em>silico</em> generation of novel ligands for the inhibition of SARS-CoV-2 main protease (3CL<sup>pro</sup>) using deep learning</strong> - The recent emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease (COVID-19) has become a global public health crisis, and a crucial need exists for rapid identification and development of novel therapeutic interventions. In this study, a recurrent neural network (RNN) is trained and optimized to produce novel ligands that could serve as potential inhibitors to the SARS-CoV-2 viral protease: 3 chymotrypsin-like protease (3CL^(pro))….</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>Synergistic Effect of Zinc-Chitosan Nanoparticles and Hydroxychloroquine to Inhibit Buffalo Coronavirus</strong> - Zinc ions can hinder the synthesis of proteins required for accomplishing several stages of the viral life cycle. The intracellular zinc concentration can be increased by using zinc ionophores which transport zinc ions into the cells and hinder viral replication. (Hydroxy)chloroquine is an example of a zinc ionophore, but both zinc and (hydroxy)chloroquine can be toxic to the host organism. The nanocarriers may serve as camouflage to evade the adverse effects of drugs, chemicals, and…</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>Auraptene Has Antiviral Activity against Human Coronavirus OC43 in MRC-5 Cells</strong> - Auraptene (7-geranyloxycoumarin) is the abundant prenyloxycoumarin found in the fruits of Citrus spp. Auraptene has a variety of pharmacological and therapeutic functions, such as anticancer, antioxidant, immunomodulatory, and anti-inflammation activities, with excellent safety profiles. In this study, we evaluated the anticoronaviral activity of auraptene in HCoV-OC43-infected human lung fibroblast MRC-5 cells. We found that auraptene effectively inhibited HCoV-OC43-induced cytopathic effects…</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>Potency of Xanthone Derivatives from <em>Garcinia mangostana</em> L. for COVID-19 Treatment through Angiotensin-Converting Enzyme 2 and Main Protease Blockade: A Computational Study</strong> - ACE2 and Mpro in the pathology of SARS-CoV-2 show great potential in developing COVID-19 drugs as therapeutic targets, due to their roles as the “gate” of viral entry and viral reproduction. Of the many potential compounds for ACE2 and Mpro inhibition, α-mangostin is a promising candidate. Unfortunately, the potential of α-mangostin as a secondary metabolite with the anti-SARS-CoV-2 activity is hindered due to its low solubility in water. Other xanthone isolates, which also possess the xanthone…</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>Pharmacological Activity of Cepharanthine</strong> - Cepharanthine, a natural bisbenzylisoquinoline (BBIQ) alkaloid isolated from the plant Stephania Cephalantha Hayata, is the only bisbenzylisoquinoline alkaloid approved for human use and has been used in the clinic for more than 70 years. Cepharanthine has a variety of medicinal properties, including signaling pathway inhibitory activities, immunomodulatory activities, and antiviral activities. Recently, cepharanthine has been confirmed to greatly inhibit SARS-CoV-2 infection. Therefore, we…</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>Aprotinin-Drug against Respiratory Diseases</strong> - Aprotinin (APR) was discovered in 1930. APR is an effective pan-protease inhibitor, a typical “magic shotgun”. Until 2007, APR was widely used as an antithrombotic and anti-inflammatory drug in cardiac and noncardiac surgeries for reduction of bleeding and thus limiting the need for blood transfusion. The ability of APR to inhibit proteolytic activation of some viruses leads to its use as an antiviral drug for the prevention and treatment of acute respiratory virus infections. However, due to…</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>Transcriptome Changes of Hematopoietic Stem and Progenitor Cells in the Peripheral Blood of COVID-19 Patients by scRNA-seq</strong> - Coronavirus disease 2019 (COVID-19) threatens public health all over the world. It is well-accepted that the immune cells in peripheral blood are widely involved in the pathological process of COVID-19. However, hematopoietic stem and progenitor cells (HSPCs), as the main source of peripheral immune cells, have not been well studied during COVID-19 infection. We comprehensively revealed the transcriptome changes of peripheral blood HSPCs after COVID-19 infection and vaccination by single-cell…</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 Multivariant Surrogate Neutralization Assay Identifies Variant-Specific Neutralizing Antibody Profiles in Primary SARS-CoV-2 Omicron Infection</strong> - Primary infection with the Omicron variant of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) can be serologically identified with distinct profiles of neutralizing antibodies (nAbs), as indicated by high titers against the Omicron variant and low titers against the ancestral wild-type (WT). Here, we evaluated whether a novel surrogate virus neutralization assay (sVNT) that simultaneously quantifies the binding inhibition of angiotensin-converting enzyme 2 (ACE2) to the proteins of…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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