189 lines
54 KiB
HTML
189 lines
54 KiB
HTML
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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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>A suggested method to disrupt SARS-CoV-2 spikes using ketone bodies in analogy to the effect of biocidal agents.</strong> -
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Biocidal agents such as formaldehyde and glutaraldehyde are able to inactivate several coronaviruses including SARS-CoV-2. In this article, an insight into the mechanism of inactivation of these viruses by those two agents is presented, based on analysis of previous observations during electron microscopic examination of several members of the orthocoronavirinae subfamily, including the new virus SARS-CoV-2. This inactivation is proposed to occur through Schiff base reaction-induced conformational changes in the spike glycoprotein leading to its separation from the virion. Also, a new prophylactic and therapeutic measure using acetoacetate is proposed, suggesting that it could similarly break the viral spike through Schiff base reaction with lysines of the spike protein. This measure needs to be confirmed experimentally before consideration. In addition, a new line of research is proposed to help find a broad spectrum antivirus against several members of of this subfamily.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/fv3bq/" target="_blank">A suggested method to disrupt SARS-CoV-2 spikes using ketone bodies in analogy to the effect of biocidal agents.</a>
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<li><strong>Paired heavy and light chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses</strong> -
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Understanding protective mechanisms of antibody recognition can inform vaccine and therapeutic strategies against SARS-CoV-2. We discovered a new antibody, 910-30, that targets the SARS-CoV-2 ACE2 receptor binding site as a member of a public antibody response encoded by IGHV3-53/IGHV3-66 genes. We performed sequence and structural analyses to explore how antibody features correlate with SARS-CoV-2 neutralization. Cryo-EM structures of 910-30 bound to the SARS-CoV-2 spike trimer revealed its binding interactions and ability to disassemble spike. Despite heavy chain sequence similarity, biophysical analyses of IGHV3-53/3-66 antibodies highlighted the importance of native heavy:light pairings for ACE2 binding competition and for SARS-CoV-2 neutralization. We defined paired heavy:light sequence signatures and determined antibody precursor prevalence to be ~1 in 44,000 human B cells, consistent with public antibody identification in several convalescent COVID-19 patients. These data reveal key structural and functional neutralization features in the IGHV3-53/3-66 public antibody class to accelerate antibody-based medical interventions against SARS-CoV-2.
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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/10.1101/2020.12.31.424987v1" target="_blank">Paired heavy and light chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses</a>
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<li><strong>Direct detection of SARS-CoV-2 RNA using high-contrast pH-sensitive dyes</strong> -
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<div>
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The worldwide COVID-19 pandemic has had devastating effects on health, healthcare infrastructure, social structure, and economics. One of the limiting factors in containing the spread of this virus has been the lack of widespread availability of fast, inexpensive, and reliable methods for testing of individuals. Frequent screening for infected and often asymptomatic people is a cornerstone of pandemic management plans. Here, we introduce two pH sensitive ″LAMPshade″ dyes as novel readouts in an isothermal RT-LAMP amplification assay for SARS-CoV-2 RNA. The resulting JaneliaLAMP (jLAMP) assay is robust, simple, inexpensive, has low technical requirements and we describe its use and performance in direct testing of contrived and clinical samples without RNA extraction.
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</p>
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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/10.1101/2020.12.26.20248878v1" target="_blank">Direct detection of SARS-CoV-2 RNA using high-contrast pH-sensitive dyes</a>
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<li><strong>Marine Debris Mitigation – Plastic Neutrality through a Credit System in Southeast Asia</strong> -
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<div>
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Sustainable Development Goals (SDG) 12: Responsible consumption and production and 14: Life Below Water coincide in the targeting of the problem of plastic marine litter, which has been garnering immense media attention in the recent years. In the Bangkok Declaration of 2019, the Association of Southeast Asian Nations (ASEAN) vowed to significantly reduce marine litter. Efforts to reduce unnecessary plastic consumption have been seen in social movements, corporate policies and most noticeably, in regulatory control in the form of bans for specific types of single-use plastic items. A paradox exists as, arguably, civilization cannot sustain its current developmental momentum without the use of plastics, especially with the COVID-19 pandemic demanding higher levels of hygiene. This is the argument that is seen coupled with mass bans of single-use plastics, including packaging material and personal protective equipment. Corporate engagement to manage the plastic value chain in ways that commit to the creation of circular economies is attaining popularity. While reduction and substitution are being considered, the status quo of the scale of the production of plastics is still expected for the next few years as life cycle assessments (LCA), test trials of consumer acceptance towards novel delivery mechanisms and other forms of innovation are emerging. The reduction of plastics in the private-sector is allegedly ongoing but intangible in Southeast Asia. While recovery and collection innovations are underway for application and picking up speed, an unfathomable rate of marine litter entering waterways is still aggravating the bigger-than-ever problem of plastic marine debris in Southeast Asia. Responsible production has long adopted the concept of credits. Carbon credits are the most notable one, while palm oil credits are also prominently purchased by manufacturers to offset any palm oil content that is not yet sourced from certified sustainable suppliers. The concept of credits for plastics has been proposed but remains much less explored than their counterparts for other commodities. “Plastic neutrality” in the form of credit purchasing by manufacturers could likely be the final missing piece of the puzzle picturing a circular economy. In theory, the credit system could serve as an offsetting mechanism to recover from nature an equivalent or higher amount of plastics to be produced by the credit-purchasing responsible manufacturer. This paper explores how plastic neutrality through Plastic Credits, similar to the existing carbon and sustainable palm oil credits, could be applied in Southeast Asia.
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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/jqfbm/" target="_blank">Marine Debris Mitigation – Plastic Neutrality through a Credit System in Southeast Asia</a>
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<li><strong>Decline in Marriage Associated with the COVID-19 Pandemic in the United States</strong> -
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In the social upheaval arising from the COVID-19 pandemic, we do not yet know how union formation, particularly marriage, has been affected. Using administration records - marriage certificates and applications - gathered from settings representing a variety of COVID-19 experiences in the United States, we compare counts of recorded marriages in 2020 against those from the same period in 2019. We find a dramatic decrease in year-to-date cumulative marriages in 2020 compared to 2019 in each case. Similar patterns are observed for the Seattle metropolitan area when we analyze the cumulative number of marriage applications, a leading indicator of marriages in the near future. Year-to-date declines in marriage are unlikely to be solely due to closure of government agencies that administer marriage certification or reporting delays. Together, these findings suggest marriage has declined during the COVID-19 outbreak and may continue to do so, at least in the short term.
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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/x6ph4/" target="_blank">Decline in Marriage Associated with the COVID-19 Pandemic in the United States</a>
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<li><strong>Nonspecific blood tests as proxies for COVID-19 hospitalization: are there plausible associations after excluding noisy predictors?</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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This study applied causal criteria in directed acyclic graphs for handling covariates in associations for prognosis of severe COVID-19 (Corona virus disease 19) cases. To identify nonspecific blood tests and risk factors as predictors of hospitalization due to COVID-19, one has to exclude noisy predictors by comparing the concordance statistics (AUC) for positive and negative cases of SARS-CoV-2 (acute respiratory syndrome coronavirus 2). Predictors with significant AUC at negative stratum should be either controlled for their confounders or eliminated (when confounders are unavailable). Models were classified according to the difference of AUC between strata. The framework was applied to an open database with 5644 patients from Hospital Israelita Albert Einstein in Brazil with SARS-CoV-2 RT-PCR (Reverse Transcription - Polymerase Chain Reaction) exam. C-reactive Protein (CRP) was a noisy predictor: hospitalization could have happen due to causes other than COVID-19 even when SARS-CoV-2 RT-PCR is positive and CRP is reactive, as most cases are asymptomatic to mild. Candidates of characteristic response from moderate to severe inflammation of COVID-19 were: combinations of eosinophils, monocytes and neutrophils, with age as risk factor; and creatinine, as risk factor, sharpens the odds ratio of the model with monocytes, neutrophils, and age.
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</p>
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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.medrxiv.org/content/10.1101/2020.10.12.20211557v2" target="_blank">Nonspecific blood tests as proxies for COVID-19 hospitalization: are there plausible associations after excluding noisy predictors?</a>
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<li><strong>The evaluation of a newly developed antigen test (QuickNavi™-COVID19 Ag) for SARS-CoV-2: A prospective observational study in Japan</strong> -
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<b>Introduction</b> Several antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed worldwide, but their clinical utility has not been well established. In this study, we evaluated the analytical and clinical performance of QuickNavi™-COVID19 Ag, a newly developed antigen test in Japan. <b>Methods</b> This prospective observational study was conducted at a PCR center between October 7 and December 5, 2020. The included patients were referred from a local public health center and 89 primary care facilities. We simultaneously obtained two nasopharyngeal samples with flocked swabs; one was used for the antigen test and the other for real-time reverse transcription PCR (RT-PCR). Using the results of real-time RT-PCR as a reference, the performance of the antigen test was evaluated. <b>Results</b> A total of 1186 patients were included in this study, and the real-time RT-PCR detected SARS-CoV-2 in 105 (8.9%). Of these 105 patients, 33 (31.4%) were asymptomatic. The antigen test provided a 98.8% (95% confident interval [CI]: 98.0%-99.4%) concordance rate with real-time RT-PCR, along with a sensitivity of 86.7% (95% CI: 78.6%-92.5%) and a specificity of 100% (95% CI: 99.7%-100%). False-negatives were observed in 14 patients, 8 of whom were asymptomatic and had a low viral load (cycle threshold (Ct) >30). In symptomatic patients, the sensitivity was 91.7% (95% CI: 82.7%-96.9%). <b>Conclusion</b> QuickNavi™-COVID19 Ag showed high specificity and sufficient sensitivity for the detection of SARS-CoV-2. This test is a promising potential diagnostic modality especially in symptomatic patients.
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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/10.1101/2020.12.27.20248876v2" target="_blank">The evaluation of a newly developed antigen test (QuickNavi™-COVID19 Ag) for SARS-CoV-2: A prospective observational study in Japan</a>
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<li><strong>Face masks, old age, and obesity explain country's COVID-19 death rates</strong> -
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We tested the hypothesis that not wearing face masks, old age, and obesity can largely explain COVID-19 death rates across countries. In the regression analysis, they contributed to 61.5%, 40.5%, and 43.8%, respectively, and a model including all these variables contributed to 70.2% of the variation in the cumulative number of COVID-19 deaths per million on May 13, 2020, in 22 countries. We also proposed the hypothesis that these variables may be confounders of other suspected factors with large differences between Western and non-Western countries, such as the BCG vaccination policy. These results contribute to the elucidation of differences in COVID-19 death rates between countries and support a suspected causal effect of face masks.
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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/10.1101/2020.06.22.20137745v5" target="_blank">Face masks, old age, and obesity explain country's COVID-19 death rates</a>
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<li><strong>Country-level Determinants of the Severity of the First Global Wave of the COVID-19 Pandemic: An Ecological Study</strong> -
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Objective: We aimed to identify the country-level determinants of the severity of the first wave of the COVID-19 pandemic. Design: An ecological study design of publicly available data was employed. Countries reporting >25 COVID-related deaths until 08/06/2020 were included. The outcome was log mean mortality rate from COVID-19, an estimate of the country-level daily increase in reported deaths during the ascending phase of the epidemic curve. Potential determinants assessed were most recently published demographic parameters (population and population density, percentage population living in urban areas, median age, average body mass index, smoking prevalence), Economic parameters (Gross Domestic Product per capita); environmental parameters: pollution levels, mean temperature (January-May)), co- morbidities (prevalence of diabetes, hypertension and cancer), health system parameters (WHO Health Index and hospital beds per 10,000 population); international arrivals, the stringency index, as a measure of country-level response to COVID-19, BCG vaccination coverage, UV radiation exposure and testing capacity. Multivariable linear regression was used to analyse the data. Primary Outcome: Country-level mean mortality rate: the mean slope of the COVID-19 mortality curve during its ascending phase. Participants: Thirty-seven countries were included: Algeria, Argentina, Austria, Belgium, Brazil, Canada, Chile, Colombia, the Dominican Republic, Ecuador, Egypt, Finland, France, Germany, Hungary, India, Indonesia, Ireland, Italy, Japan, Mexico, the Netherlands, Peru, the Philippines, Poland, Portugal, Romania, the Russian Federation, Saudi Arabia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom and the United States. Results: Of all country-level predictors included in the multivariable model, total number of international arrivals (beta 0.033 (95% Confidence Interval 0.012,0.054)) and BCG vaccination coverage (-0.018 (-0.034,-0.002)), were significantly associated with the mean death rate. Conclusions: International travel was directly associated with the mortality slope and thus potentially the spread of COVID-19. Very early restrictions on international travel should be considered to control COVID outbreak and prevent related deaths.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.05.13.20100677v3" target="_blank">Country-level Determinants of the Severity of the First Global Wave of the COVID-19 Pandemic: An Ecological Study</a>
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<li><strong>Assessing concerns for the economic consequence of the COVID-19 response and mental health problems associated with economic vulnerability and negative economic shock in Italy, Spain, and the United Kingdom</strong> -
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Currently, many different countries are under lockdown or extreme social distancing measures to control the spread of COVID-19. The potentially far-reaching side effects of these measures have not yet been fully understood. In this study we analyse the results of a multi-country survey conducted in Italy (N=3,504), Spain (N=3,524) and the United Kingdom (N=3,523), with two separate analyses. In the first analysis, we examine the elicitation of citizens’ concerns over the downplaying of the economic consequences of the lockdown during the COVID-19 pandemic. We control for Social Desirability Bias through a list experiment included in the survey. In the second analysis, we examine the data from the same survey to estimate the consequences of the economic lockdown in terms of mental health, by predicting the level of stress, anxiety and depression associated with being economically vulnerable and having been affected by a negative economic shock. To accomplish this, we have used a prediction algorithm based on machine learning techniques. To quantify the size of this affected population, we compare its magnitude with the number of people affected by COVID-19 using measures of susceptibility, vulnerability and behavioural change collected in the same questionnaire. We find that the concern for the economy and for “the way out” of the lockdown is diffuse and there is evidence of minor underreporting. Additionally, we estimate that around 42.8% of the populations in the three countries are at high risk of stress, anxiety and depression, based on their level of economic vulnerability and their exposure to a negative economic shock. Therefore, it can be concluded that the lockdown and extreme social distancing in the three countries has had an enormous impact on individuals’ mental health and this should be taken into account for future decisions made on regulations concerning the pandemic.
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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/x9m36/" target="_blank">Assessing concerns for the economic consequence of the COVID-19 response and mental health problems associated with economic vulnerability and negative economic shock in Italy, Spain, and the United Kingdom</a>
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<li><strong>Connected Despite COVID-19: The Role of Social Interactions and Social Media for Wellbeing</strong> -
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Physical distancing is crucial for slowing the spread of COVID-19, but the associated reduction of social interaction can be detrimental to psychological wellbeing. Here, we sought to understand whether different ways in which people connect to others might mitigate this negative impact. We examined how amount and type of social interactions and social media use would predict wellbeing during a period of physical distancing in the United Kingdom. In a 30-day diary study conducted in April-June 2020, 108 participants reported their daily social interactions and social media use, as well as their end-of-day wellbeing. Using multilevel regressions, we found that more face-to-face interactions positively predicted wellbeing, while technology-mediated communication had less consistent positive effects on wellbeing. More active and less passive social media use was associated with greater wellbeing. Our results suggest that while technology-mediated communication can improve wellbeing, face-to-face interactions are unique and important for wellbeing during physical distancing.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/x5k8u/" target="_blank">Connected Despite COVID-19: The Role of Social Interactions and Social Media for Wellbeing</a>
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<li><strong>Unusual public pressure on retraction decision during crisis</strong> -
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During the COVID-19 pandemic, the mainstream media and social media may have imposed more pressure on retraction decision of COVID-19 related academic papers.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/h5tbf/" target="_blank">Unusual public pressure on retraction decision during crisis</a>
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<li><strong>Airborne Transmission of Virus-Laden Aerosols inside a Music Classroom: Effects of Portable Purifiers and Aerosol Injection Rates</strong> -
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The ongoing COVID-19 pandemic has shifted attention to the airborne transmission of exhaled droplet nuclei within indoor environments. The spread of aerosols through singing and musical instruments in music performances has necessitated precautionary methods such as masks and portable purifiers. This study investigates the effects of placing portable air purifiers at different locations inside a classroom, as well as the effects of different aerosol injection rates (e.g., with and without masks, different musical instruments and different injection modes). Aerosol deposition, airborne concentration and removal are analyzed in this study. It was found that using purifiers could help in achieving ventilation rates close to the prescribed values by the World Health Organization (WHO), while also achieving aerosol removal times within the Center of Disease Control and Prevention (CDC) recommended guidelines. This could help in deciding break periods between classroom sessions, which was around 25 minutes through this study. Moreover, proper placement of purifiers could offer significant advantages in reducing airborne aerosol numbers (offering orders of magnitude higher aerosol removal when compared to nearly zero removal when having no purifiers), and improper placement of the purifiers could worsen the situation. The study suggests the purifier to be placed close to the injector to yield a benefit, and away from the people to be protected. The injection rate was found to have an almost linear correlation with the average airborne aerosol suspension rate and deposition rate, which could be used to predict the trends for scenarios with other injection rates.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.19.20248374v4" target="_blank">Airborne Transmission of Virus-Laden Aerosols inside a Music Classroom: Effects of Portable Purifiers and Aerosol Injection Rates</a>
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<li><strong>Using Predictive Analytics for Public Policy: The Case for Lost Work due to the COVID-19</strong> -
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In this brief research article, I demonstrate how predictive analytics or machine learning can be used to predict outcomes that are of interest in public policy. I developed a predictive model that determined who were not able to work during the past four weeks because the COVID-19 pandemic led their employer to close or lose business. I used the Current Population Survey (CPS) collected from May to November 2020 (N=352,278). Predictive models considered were logistic regression and ensemble-based methods (bagging of regression trees, random forests, and boosted regression trees). Predictors included (1) individual-, (2) family-, (3) and community or societal- level factors. To validate the models, I used the random training test splits with equal allocation of samples for the training and testing data. The random forest with the full set of predictors and number of splits set to the square root of the number of predictors yielded the lowest testing error rate. Predictive analytics that seek to forecast the inability to work due to the pandemic can be used for automated means-testing to determine who gets aid like unemployment benefits or food stamps.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/e5z73/" target="_blank">Using Predictive Analytics for Public Policy: The Case for Lost Work due to the COVID-19</a>
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<li><strong>Rapid inactivation of SARS-CoV-2 on copper touch surfaces determined using a cell culture infectivity assay</strong> -
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COVID-19, caused by SARS-CoV-2, was first reported in China in 2019 and has transmitted rapidly around the world, currently responsible for 83 million reported cases and over 1.8 million deaths. The mode of transmission is believed principally to be airborne exposure to respiratory droplets from symptomatic and asymptomatic patients but there is also a risk of the droplets contaminating fomites such as touch surfaces including door handles, stair rails etc, leading to hand pick up and transfer to eyes, nose and mouth. We have previously shown that human coronavirus 229E survives for more than 5 days on inanimate surfaces and another laboratory reproduced this for SARS-CoV-2 this year. However, we showed rapid inactivation of Hu-CoV-229E within 10 minutes on different copper surfaces while the other laboratory indicated this took 4 hours for SARS-CoV-2. So why the difference? We have repeated our work with SARS-CoV-2 and can confirm that this coronavirus can be inactivated on copper surfaces in as little as 1 minute. We discuss why the 4 hour result may be technically flawed.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.02.424974v1" target="_blank">Rapid inactivation of SARS-CoV-2 on copper touch surfaces determined using a cell culture infectivity assay</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>Dendritic Cell Vaccine to Prevent COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: AV-COVID-19<br/><b>Sponsors</b>: Indonesia-MoH; Aivita Biomedical, Inc.; PT AIVITA Biomedika Indonesia; National Institute of Health Research and Development, Ministry of Health Republic of Indonesia; RSUP Dr. Kariadi Semarang, indonesia; Faculty of Medicine University of Diponegoro, Indonesia<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>Effect of Dalcetrapib in Patients With Confirmed Mild to Moderate COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Dalcetrapib; Other: Placebo<br/><b>Sponsors</b>: DalCor Pharmaceuticals; The Montreal Health Innovations Coordinating Center (MHICC); Covance<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>suPAR-Guided Anakinra Treatment for Management of Severe Respiratory Failure by COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Anakinra; Drug: Placebo<br/><b>Sponsor</b>: Hellenic Institute for the Study of Sepsis<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>Evaluating the Impact of EnteraGam In People With COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Dietary Supplement: Bovine Plasma-Derived Immunoglobulin Concentrate; Other: Standard of care<br/><b>Sponsors</b>: Entera Health, Inc; Lemus Buhils, SL; Clinical Research Unit, IMIM (Hospital del Mar Medical Research Institute)<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 and Safety of Remdesivir and Tociluzumab for the Management of Severe COVID-19: A Randomized Controlled Trial</strong> - <b>Conditions</b>: Covid19; Covid-19 ARDS<br/><b>Interventions</b>: Drug: Remdesivir; Drug: Tocilizumab<br/><b>Sponsors</b>: M Abdur Rahim Medical College and Hospital; First affiliated Hospital of Xi'an Jiaoting University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhaled Ivermectin and COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Ivermectin Powder<br/><b>Sponsor</b>: Mansoura University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Tenofovir/Emtricitabine in Patients Recently Infected With SARS-COV2 (Covid-19) Discharged Home</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: tenofovir disoproxil and emtricitabine<br/><b>Sponsor</b>: University Hospital, Caen<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>Safety and Immunogenicity of Two Different Strengths of the Inactivated COVID 19 Vaccine ERUCOV-VAC</strong> - <b>Condition</b>: COVID-19 Vaccine<br/><b>Interventions</b>: Biological: ERUCOV-VAC; Other: Placebo Vaccine<br/><b>Sponsors</b>: Health Institutes of Turkey; TC Erciyes University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>AZD1222 Vaccine in Combination With rAd26-S, Recombinant Adenovirus Type 26 Component of Gam-COVID-Vac Vaccine, for the Prevention of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: AZD1222; Biological: rAd26-S<br/><b>Sponsors</b>: AstraZeneca; R-Pharm<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>Anti-COVID19 AKS-452 - ACT Study</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Biological: AKS-452<br/><b>Sponsors</b>: University Medical Center Groningen; Akston Biosciences Corporation<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>Study in Adults to Determine the Safety and Immunogenicity of AZD1222, a Non-replicating ChAdOx1 Vector Vaccine, Given in Combination With rAd26-S, Recombinant Adenovirus Type 26 Component of Gam-COVID-Vac Vaccine, for the Prevention of COVID-19.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: AZD1222; Biological: rAd26-S<br/><b>Sponsors</b>: R-Pharm; AstraZeneca<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>Surgical Face Mask Effects in Patients With COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Other: Sit-To-Stand test<br/><b>Sponsor</b>: Cliniques universitaires Saint-Luc- Université Catholique de Louvain<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>Dendritic Cell Vaccine, AV-COVID-19, to Prevent COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: AV-COVID-19; Other: GM-CSF<br/><b>Sponsors</b>: Aivita Biomedical, Inc.; PT AIVITA Biomedika Indonesia; Indonesia Ministry of Health; National Institute of Health Research and Development, Ministry of Health Republic of Indonesia<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of hzVSF-v13 in Patients With COVID-19 Pneumonia</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: hzVSF-v13; Drug: Placebo (Normal saline solution)<br/><b>Sponsor</b>: ImmuneMed, Inc.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Clinical Study to Assess the Efficacy and Safety of Amizon® Max in the Treatment of Moderate Covid-19</strong> - <b>Condition</b>: Covid-19 Disease<br/><b>Interventions</b>: Drug: Enisamium Iodide; Drug: Placebo<br/><b>Sponsor</b>: Joint Stock Company "Farmak"<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<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>ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels: a Mendelian randomization study</strong> - Angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 have been implicated in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). The expression of ACE2 and TMPRSS2 in the lung epithelium might have implications for the risk of SARS-CoV-2 infection and severity of COVID-19. We use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk...</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>Hydroxychloroquine as a Chemoprophylactic Agent for COVID-19: A Clinico-Pharmacological Review</strong> - Hydroxychloroquine has gained much attention as one of the candidate drugs that can be repurposed as a prophylactic agent against SARS-CoV-2, the agent responsible for the COVID-19 pandemic. Due to high transmissibility and presence of asymptomatic carriers and presymptomatic transmission, there is need for a chemoprophylactic agent to protect the high-risk population. In this review, we dissect the currently available evidence on hydroxychloroquine prophylaxis from a clinical 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>Potential Simultaneous Inhibitors of Angiotensin-Converting Enzyme 2 and Transmembrane Protease, Serine 2</strong> - Outbreak of coronavirus disease 2019 occurred in Wuhan and has rapidly spread to almost all parts of world. GB-1, the herbal formula from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, is used for the prophylaxis of SARS-CoV-2 in Taiwan. In this study, we investigated that the effect of GB-1 and the index compounds of GB-1 on the ACE2 and TMPRSS2 expression through in vitro and in vivo study. In our result, GB-1 can inhibit ACE2 and TMPRSS2 protein expression in HepG2 cells, 293T cells, 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>Excited-state electronic properties, structural studies, noncovalent interactions, and inhibition of the novel severe acute respiratory syndrome coronavirus 2 proteins in Ripretinib by first-principle simulations</strong> - Ripretinib is a recently developed drug for the treatment of adults with advanced gastrointestinal stromal tumors. This paper reports an attempt to study this molecule by electronic modeling and molecular mechanics to determine its composition and other specific chemical features via the density-functional theory (DFT), thereby affording sufficient information on the electronic properties and descriptors that can enable the estimation of its molecular bioactivity. We explored most of the...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Synthesis of novel indolo[3,2-c]isoquinoline derivatives bearing pyrimidine, piperazine rings and their biological evaluation and docking studies against COVID-19 virus main protease</strong> - A series of hybrid indolo[3,2-c]isoquinoline (δ-carboline) analogs incorporating two pyrimidine and piperizine ring frameworks were synthesized. Intending biological activities and SAR we propose replacements of fluorine, methyl and methoxy of synthetic compounds for noteworthy antimicrobial, antioxidant, anticancer and anti-tuberculosis activities. Among these compounds 3a, 4a and 5e were progressively strong against E. coli and K. pneumonia. Whereas, compounds 4a, 5a and 6a with addition of...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Tetracycline plus macrolide: A potential therapeutic regimen for COVID-19?</strong> - The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that struck in late 2019 and early 2020 is a serious threat to human health. Since there are no approved drugs that satisfactorily treat this condition, all efforts at drug design and/or clinical trials are warranted and reasonable. Drug repurposing is a well-known strategy that seeks to deploy existing licensed drugs for newer indications and that provides the quickest possible transition from the bench...</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>Oral nano-curcumin formulation efficacy in management of mild to moderate hospitalized coronavirus disease-19 patients: An open label nonrandomized clinical trial</strong> - Curcumin is proposed as a potential treatment option for coronavirus disease-19 (COVID-19) by inhibiting the virus entrance, encapsulation and replication, and modulating various cellular signaling pathways. In this open-label nonrandomized clinical trial, efficacy of nano-curcumin oral formulation has been evaluated in hospitalized patients with mild-moderate COVID-19. Forty-one patients who fulfilled the inclusion criteria were allocated to nano-curcumin (n = 21) group (Sinacurcumin soft gel,...</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>CoViTris2020 and ChloViD2020: a striking new hope in COVID-19 therapy</strong> - Designing anticoronavirus disease 2019 (anti-COVID-19) agents is the primary concern of medicinal chemists/drug designers nowadays. Repurposing of known active compounds against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new effective and time-saving trend in anti-COVID-19 drug discovery. Thorough inhibition of the coronaviral-2 proteins (i.e., multitarget inhibition) is a possible powerful favorable strategy for developing effectively potent drugs for COVID-19. In...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Remdesivir: From Ebola to COVID-19</strong> - Human coronaviruses (HCoV) were discovered in the 1960s and were originally thought to cause only mild upper respiratory tract diseases in immunocompetent hosts. This view changed since the beginning of this century, with the 2002 SARS (severe acute respiratory syndrome) epidemic and the 2012 MERS (Middle East respiratory syndrome) outbreak, two zoonotic infections that resulted in mortality rates of approximately 10% and 35%, respectively. Despite the importance of these pathogens, no approved...</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>Propedia: a database for protein-peptide identification based on a hybrid clustering algorithm</strong> - CONCLUSIONS: Propedia is a database and tool to support structure-based rational design of peptides for special purposes. Protein-peptide interactions can be useful to predict, classifying and scoring complexes or for designing new molecules as well. Propedia is up-to-date as a ready-to-use webserver with a friendly and resourceful interface and is available at: https://bioinfo.dcc.ufmg.br/propedia.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of a commercially-available surrogate virus neutralization test for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)</strong> - There remains an urgent need for assays to quantify humoral protective immunity to SARS-CoV-2 to understand the immune responses of COVID-19 patients, evaluate efficacy of vaccine candidates in clinical trials, and conduct large-scale epidemiological studies. The plaque-reduction neutralization test (PRNT) is the reference-standard for quantifying antibodies capable of neutralizing SARS-CoV-2. However, the PRNT is logistically demanding, time-consuming, and requires containment level-3...</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>In silico study of the potential interactions of 4'-acetamidechalcones with protein targets in SARS-CoV-2</strong> - The sanitary emergency generated by the pandemic COVID-19, instigates the search for scientific strategies to mitigate the damage caused by the disease to different sectors of society. The disease caused by the coronavirus, SARS-CoV-2, reached 216 countries/territories, where about 20 million people were reported with the infection. Of these, more than 740,000 died. In view of the situation, strategies involving the development of new antiviral molecules are extremely important. The present work...</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>Dexamethasone inhibits SARS-CoV-2 spike pseudotyped virus viropexis by binding to ACE2</strong> - The SARS-CoV-2 outbreak, began in late 2019, has caused a worldwide pandemic and shows no signs of slowing. Glucocorticoids (GCs), including dexamethasone (DEX), have been widely used as effective anti-inflammatory and immunosuppressant drugs. In this study, seven GCs had no obvious effect on cell viability of angiotensin converting enzyme 2 (ACE2) high expressed HEK293T cells when concentrations were under 10 μM. Molecular docking results revealed that DEX occupied with active binding site of...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of the replication of SARS-CoV-2 in human cells by the FDA-approved drug chlorpromazine</strong> - CONCLUSIONS: These preclinical findings support clinical investigation of the repurposing of CPZ, a largely used drug with mild side effects, in COVID-19 treatment.</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>Unraveling the mechanism of arbidol binding and inhibition of SARS-CoV-2: Insights from atomistic simulations</strong> - The COVID-19 pandemic has spread rapidly and posed an unprecedented threat to the global economy and human health. Broad-spectrum antivirals are currently being administered to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). China's prevention and treatment guidelines suggest the use of an antiinfluenza drug, arbidol, for the clinical treatment of COVID-19. Reports indicate that arbidol could neutralize SARS-CoV-2. Monotherapy with arbidol is found to be superior to...</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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<ul>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Covid 19 - Chewing Gum</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313269181">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A traditional Chinese medicine composition for COVID-19 and/or influenza and preparation method thereof</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313300659">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>STOCHASTIC MODEL METHOD TO DETERMINE THE PROBABILITY OF TRANSMISSION OF NOVEL COVID-19</strong> - The present invention is directed to a stochastic model method to assess the risk of spreading the disease and determine the probability of transmission of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN313339294">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313251184">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313251182">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>"AYURVEDIC PROPRIETARY MEDICINE FOR TREATMENT OF SEVERWE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2."</strong> - AbstractAyurvedic Proprietary Medicine for treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)In one of the aspect of the present invention it is provided that Polyherbal combinations called Coufex (syrup) is prepared as Ayurvedic Proprietary Medicine , Aqueous Extracts Mixing with Sugar Syrup form the following herbal aqueous extract coriandrum sativum was used for the formulation of protek.Further another Polyherbal combination protek as syrup is prepared by the combining an aqueous extract of the medicinal herbs including Emblica officinalis, Terminalia chebula, Terminalia belerica, Aegle marmelos, Zingiber officinale, Ocimum sanctum, Adatoda zeylanica, Piper lingum, Andrographis panivulata, Coriandrum sativum, Tinospora cordiofolia, cuminum cyminum,piper nigrum was used for the formulation of Coufex. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN312324209">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>제2형 중증급성호흡기증후군 코로나바이러스 감염 질환의 예방 또는 치료용 조성물</strong> - 본 발명은 화학식 1로 표시되는 화합물, 또는 이의 약학적으로 허용가능한 염; 및 글루카곤 수용체 작용제(glucagon receptor agonist), 위 억제 펩타이드(gastric inhibitory peptide, GIP), 글루카곤-유사 펩타이드 1(glucagon-like peptide 1, GLP-1) 및 글루카곤 수용체/위 억제 펩타이드/글루카곤-유사 펩타이드 1(Glucagon/GIP/GLP-1) 삼중 완전 작용제(glucagon receptors, gastric inhibitory peptide and glucagon-like peptide 1 (Glucagon/GIP/GLP-1) triple full agonist)로 이루어진 군으로부터 선택된 1종 이상;을 포함하는 제2형 중증급성호흡기증후군 코로나바이러스 감염 질환 예방 또는 치료용 약학적 조성물을 제공한다. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=KR313434044">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Haptens, hapten conjugates, compositions thereof and method for their preparation and use</strong> - A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU311608060">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 RBD共轭纳米颗粒疫苗</strong> - 本发明涉及免疫医学领域，具体而言，涉及一种SARS‑CoV‑2 RBD共轭纳米颗粒疫苗。该疫苗包含免疫原性复合物，所述免疫原性复合物包含：a）与SpyCatcher融合表达的载体蛋白自组装得到的纳米颗粒载体；b）与SpyTag融合表达的SARS‑CoV‑2病毒的RBD抗原；所述载体蛋白选自Ferritin、mi3和I53‑50；所述载体蛋白与所述抗原之间通过SpyCatcher‑SpyTag共价连接。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN313355625">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Устройство электронного контроля и дистанционного управления аппарата искусственной вентиляции легких</strong> - Полезная модель относится к медицинской технике, а именно к устройствам для воздействия на дыхательную систему пациента смесью различных газов, в частности, к устройствам для проведения искусственной вентиляции легких (ИВЛ). Технический результат предлагаемой полезной модели заключается в решении технической проблемы, состоящей в необходимости расширения арсенала технических средств, предназначенных для электронного контроля и управления ИВЛ, путем реализации возможности дистанционного управления аппаратами ИВЛ в медицинских учреждениях, не оборудованных кабельными вычислительными сетями. Указанный технический результат достигается благодаря тому, что в известное устройство электронного контроля и дистанционного управления аппарата ИВЛ, содержащее центральный микроконтроллер, а также программно-аппаратные средства управления функциями доставки воздушной смеси пациенту и многоуровневой тревожной сигнализации об отклонениях от нормативных условий и технических неполадках в аппарате ИВЛ, введены связанные друг с другом микроконтроллер связи и дистанционного управления и радиомодем, выполненный с возможностью связи с точками доступа радиканальной сети, при этом центральный микроконтроллер устройства выполнен с дополнительными входом/выходом, которые связаны с управляющими выходом/входом микроконтроллера связи и дистанционного управления, а, в зависимости от типа применяемой в медицинском учреждении радиоканальной сети связи и передачи данных, радиомодем может быть выполнен в виде интерфейсного аудиомодуля Bluetooth 4.0 BLE, приемопередающего модуля Wi-Fi либо устройства "малого радиуса действия", работающего по технологии LoRa на нелицензируемых частотах мегагерцового диапазона, например, в диапазоне 868 МГц. 3 з.п. ф-лы, 1 ил. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=RU313244211">link</a></p></li>
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