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190 lines
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<title>28 April, 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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Stent For Life Initiative in Portugal: progress through years and Covid-19 Impact</strong> -
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<div>
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Background: During Stent for Life Initiative in Portugal lifetime, positive changes in ST elevation myocardial infarction treatment were observed, by the increase of Primary Angioplasty numbers and improvements in patients’ behaviour towards myocardial infarction, with an increase in those who called 112 and the lower proportion attending non primary percutaneous coronary intervention centres. Despite public awareness campaigns and system educational programmes, patient and system delay did not change significantly over this period. The aim of this study was to address the public awareness campaign effectiveness on peoples’ behaviour facing STEMI, and how Covid-19 has affected STEMI treatment. Methods: Data from 1381 STEMI patients were collected during a one-month period each year, from 2011 to 2016, and during one and a half month, matching first lockdown in Portugal 2020. Four groups were constituted: Group A (2011); Group B (2012 & 2013); Group C (2015 & 2016) and group D (2020). Results: The proportion of patients who called 112, increased significantly (35.2% Group A; 38.7% Group B; 44.0% Group C and 49.6% Group D, p=0.005); significant reduction was observed in the proportion of patients who attended healthcare centres without PPCI (54.5% group A; 47.6% Group B; 43.2% Group C and 40.9% Group D, p=0.016), but there were no differences on groups comparison. Total ischemic time, measured from symptoms onset to reperfusion increased progressively from group A [250.0 (178.0-430.0)] to D [296.0 (201.0 – 457.5.8)] p=0.012, with statistically significant difference between group C and D (p=0.034). Conclusions: During the term of SFL initiative in Portugal, patients resorted less to primary health centres and called more to 112. These results can be attributed the public awareness campaign. Nevertheless, patient and system delays did not significantly change over this period, mainly in late years of SFL, probably for low efficacy of campaigns and in 2020 due to 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://www.medrxiv.org/content/10.1101/2023.04.25.23288494v1" target="_blank">Stent For Life Initiative in Portugal: progress through years and Covid-19 Impact</a>
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</div></li>
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<li><strong>Leveraging Machine Learning for Effective Public Health Policies: Lessons from the COVID-19 Pandemic and Future Directions in Global Health</strong> -
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<div>
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The COVID-19 pandemic has exposed the vulnerabilities of global health systems and highlighted the need for rapid, data-driven decision-making in public health. Machine learning (ML) has the potential to provide valuable insights and contribute to improved health outcomes. In this paper, we aim to explore the role of ML in global health, identify its limitations, and discuss strategies to overcome these challenges while maximizing its benefits. We conduct a comprehensive literature review and analyze case studies from the COVID-19 pandemic. Our findings indicate that ML has played a significant role in the COVID-19 response, particularly in areas such as disease modeling, drug discovery, and resource allocation. However, several limitations, including data quality and accessibility, hinder the full potential of ML in global health. We propose strategies to overcome these limitations, such as promoting data-sharing collaborations, ensuring data privacy, and fostering interdisciplinary research. This paper contributes to the ongoing conversation on the applications and limitations of ML in global health, providing insights and recommendations for researchers, practitioners, and policymakers to effectively leverage ML for improved public health outcomes.
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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/f64cn/" target="_blank">Leveraging Machine Learning for Effective Public Health Policies: Lessons from the COVID-19 Pandemic and Future Directions in Global Health</a>
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</div></li>
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<li><strong>The impact of long-term conditions and comorbidity patterns on COVID-19 infection and hospitalisation: a cohort study</strong> -
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Introduction Older adults are usually more vulnerable to COVID-19 infections; however, little is known about which comorbidity patterns are related to a higher probability of COVID-19 infection. This study investigated the role of long-term conditions or comorbidity patterns on COVID-19 infection and related hospitalisations. Methods This study included 4,428 individuals from Waves 8 (2016−2017) and 9 (2018−2019) of the English Longitudinal Study of Ageing (ELSA), who also participated in the ELSA COVID-19 Substudy in 2020. Comorbidity patterns of chronic conditions were identified using an agglomerative hierarchical clustering method. The relationships between comorbidity patterns or long-term conditions and COVID-19 related outcomes were examined using multivariable logistic regression. Results Among a representative sample of community-dwelling older adults in England, those with cardiovascular disease (CVD) and complex comorbidities had an almost double risk of COVID-19 infection (OR=1.87, 95% CI=1.42−2.46) but not of COVID-19 related hospitalisation. A similar pattern was observed for the heterogeneous comorbidities cluster (OR=1.56, 95% CI=1.24−1.96). The individual investigations of long-term conditions with COVID-19 infection highlighted primary associations with CVD (OR=1.46, 95% CI=1.23−1.74), lung diseases (OR=1.40, 95% CI=1.17−1.69), psychiatric conditions (OR=1.40, 95% CI=1.16−1.68), retinopathy/eye diseases (OR=1.39, 95% CI=1.18−1.64), and arthritis (OR=1.27, 95% CI=1.09−1.48). In contrast, metabolic disorders and diagnosed diabetes were not associated with any COVID-19 outcomes. Discussion/Conclusion This study provides novel insights into the comorbidity patterns that are more vulnerable to COVID-19 infections and highlights the importance of CVD and complex comorbidities. These findings facilitate crucial new evidence for appropriate screening measures and tailored interventions for older adults in the ongoing global outbreak.
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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/10.1101/2023.04.25.23289035v1" target="_blank">The impact of long-term conditions and comorbidity patterns on COVID-19 infection and hospitalisation: a cohort study</a>
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</div></li>
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<li><strong>Potential biomarkers for fatal outcome prognosis in a cohort of hospitalized COVID-19 patients with pre-existing co-morbidities</strong> -
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Background: The difficulty to predict fatal outcomes in COVID-19 patients, impacts in the general morbidity and mortality due to SARSCoV2 infection, as it wears out the hospital services that care for these patients. Unfortunately, in several of the candidates for prognostic biomarkers proposed, the predictive power is compromised when patients have pre-existing co-morbidities. Methods. A cohort of one hundred and forty-seven patients hospitalized for severe COVID19 was included in a descriptive, observational, single-center, and prospective study. Patients were recruited during the first COVID-19 pandemic wave (April-Nov, 2020). Data were collected from the clinical history while immunophenotyping by multiparameter flow cytometry analysis allowed us to assess the expression of surface markers on peripheral leukocytes. Patients were grouped according to the outcome in survivor or decease. The prognostic value of leukocytes, cytokines or HLA-DR, CD39, and CD73 was calculated. Results: Hypertension and chronic renal failure but not obesity and diabetes were conditions more frequent among the decease group. Mixed hypercitokinemia, including inflammatory(IL-6) and anti-inflammatory(IL-10) cytokines, was more evident in deceased patients. In the decease group, lymphopenia with a higher NLR value was present. HLA-DR expression and the percentage of CD39+ cells were higher than non COVID-19 patients, but remain similar despite outcome. ROC analysis and cut-off value of NLR (69.6%, 9.4), pNLR (71.1%, 13.6), IL-6 (79.7%, 135.2 pg/mL). Conclusion: The expression of HLA-DR, CD39, and CD73, as many serum cytokines (other than IL-6) and chemokines levels do not show prognostic potential compared to NLR and pNLR values.
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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/10.1101/2023.04.25.23288937v1" target="_blank">Potential biomarkers for fatal outcome prognosis in a cohort of hospitalized COVID-19 patients with pre-existing co-morbidities</a>
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</div></li>
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<li><strong>Broadly neutralizing antibodies targeting a conserved silent face of spike RBD resist extreme SARS-CoV-2 antigenic drift</strong> -
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<div>
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Developing broad coronavirus vaccines requires identifying and understanding the molecular basis of broadly neutralizing antibody (bnAb) spike sites. In our previous work, we identified sarbecovirus spike RBD group 1 and 2 bnAbs. We have now shown that many of these bnAbs can still neutralize highly mutated SARS-CoV-2 variants, including the XBB.1.5. Structural studies revealed that group 1 bnAbs use recurrent germline-encoded CDRH3 features to interact with a conserved RBD region that overlaps with class 4 bnAb site. Group 2 bnAbs recognize a less well-characterized “site V” on the RBD and destabilize spike trimer. The site V has remained largely unchanged in SARS-CoV-2 variants and is highly conserved across diverse sarbecoviruses, making it a promising target for broad coronavirus vaccine development. Our findings suggest that targeted vaccine strategies may be needed to induce effective B cell responses to escape resistant subdominant spike RBD bnAb sites.
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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/10.1101/2023.04.26.538488v1" target="_blank">Broadly neutralizing antibodies targeting a conserved silent face of spike RBD resist extreme SARS-CoV-2 antigenic drift</a>
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</div></li>
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<li><strong>Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market</strong> -
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<div>
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The role of the Huanan Seafood Market in the early SARS-CoV-2 outbreak remains unclear. Recently the Chinese CDC released data from deep sequencing of environmental samples collected from the market after it was closed on January-1-2020 (Liu et al, 2023). Prior to this release, Crits-Christoph et al (2023) analyzed data from a subset of the samples. Both studies concurred that the samples contained genetic material from a variety of species, including some like raccoon dogs that are susceptible to SARS-CoV-2. However, neither study systematically analyzed the relationship between the amount of genetic material from SARS-CoV-2 and different animal species. Here I implement a fully reproducible computational pipeline that jointly analyzes the number of reads mapping to SARS-CoV-2 and the mitochondrial genomes of chordate species across the full set of samples. I validate the presence of genetic material from numerous species, and calculate mammalian mitochondrial compositions similar to those reported by Crits-Christoph et al (2023). However, the number of SARS-CoV-2 reads is not consistently correlated with reads mapping to any non-human susceptible species. For instance, 14 samples have >20% of their chordate mitochondrial material from raccoon dogs, but only one of these samples contains any SARS-CoV-2 reads, and that sample only has 1 of ~200,000,000 reads mapping to SARS-CoV-2. Instead, SARS-CoV-2 reads are most correlated with reads mapping to various fish, such as catfish and largemouth bass. These results suggest that while metagenomic analysis of the environmental samples is useful for identifying animals or animal products sold at the market, co-mingling of animal and viral genetic material is unlikely to reliably indicate whether any animals were infected by 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/10.1101/2023.04.25.538336v1" target="_blank">Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market</a>
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</div></li>
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<li><strong>A systematic review of the prevalence of persistent gastrointestinal symptoms and incidence of new gastrointestinal illness after acute SARS-CoV-2 infection</strong> -
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It is known that SARS-CoV-2 infection can result in gastrointestinal symptoms. For some, these symptoms may persist beyond acute infection, in what is known as post-COVID syndrome. We conducted a systematic review to examine the prevalence of persistent gastrointestinal symptoms and the incidence of new gastrointestinal illness following acute SARS-CoV-2 infection. We searched scientific literature using MedLine, SCOPUS, Embase, Europe PubMed Central, medRxiv and Google Scholar from December 2019 to October 2022. Two reviewers independently identified 28 eligible articles which followed participants for various gastrointestinal outcomes after acute SARS-CoV-2 infection. Study quality was assessed using the Joanna Briggs Institute Critical Appraisal Tools. The weighted pooled prevalence for persistent gastrointestinal symptom of any nature and duration was 10.7%, compared to 4.9% in healthy controls. For six studies at a low risk of methodological bias, the symptom prevalence ranged from 0.2% to 24.1% with a median follow-up time of 13 weeks. We also identified the presence of functional gastrointestinal disorders in historically SARS-CoV-2 exposed individuals. Our review has shown that, from a limited pool of mostly low-quality studies, previous SARS-CoV-2 exposure may be associated with ongoing gastrointestinal symptoms and the development of functional gastrointestinal illness. Furthermore, we show the need for high-quality research to better understand the SARS-CoV-2 association with gastrointestinal symptoms, particularly as population exposure to enteric infections returns to pre-COVID-19-restriction levels.
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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/10.1101/2023.04.26.23289142v1" target="_blank">A systematic review of the prevalence of persistent gastrointestinal symptoms and incidence of new gastrointestinal illness after acute SARS-CoV-2 infection</a>
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</div></li>
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<li><strong>Comparative Cohort Study of Post-Acute Covid-19 Infection with a Nested, Randomized Controlled Trial of Ivabradine for Those With Postural Orthostatic Tachycardia Syndrome (The COVIVA Study)</strong> -
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<div>
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Background: Significant clinical similarities have been observed between the recently described Long-Haul COVID-19 (LHC) syndrome, Postural Orthostatic Tachycardia Syndrome (POTS) and Inappropriate Sinus Tachycardia (IST). Shared symptoms include light-headedness, palpitations, tremulousness, generalized weakness, blurred vision, chest pain, dyspnea, brain-fog, and fatigue. Ivabradine is a selective sinoatrial node blocker FDA-approved for management of tachycardia associated with stable angina and heart failure not fully managed by beta blockers. In our study we aim to identify risk factors underlying LHC, as well as the effectiveness of ivabradine in controlling heart rate dysregulations and POTS/IST related symptoms. Methods/Design: A detailed prospective phenotypic evaluation combined with multi-omic analysis of 200 LHC volunteers will be conducted to identify risk factors for autonomic dysfunction. A comparator group of 50 volunteers with documented COVID-19 but without LHC will be enrolled to better understand the risk factors for LHC and autonomic dysfunction. Those in the cohort who meet diagnostic criteria for POTS or IST will be included in a nested prospective, randomized, placebo-controlled trial to assess the impact of ivabradine on symptoms and heart rate, assessed non-invasively based on physiologic response and ambulatory electrocardiogram. Additionally, studies on catecholamine production, mast cell and basophil degranulation, inflammatory biomarkers, and indicators of metabolic dysfunction will be measured to potentially provide molecular classification and mechanistic insights. Discussion: Optimal therapies for dysautonomia, particularly associated with LHC, have yet to be defined. In the present study, ivabradine, one of numerous proposed interventions, will be systematically evaluated for therapeutic potential in LHC-associated POTS and IST. Additionally, this study will further refine the characteristics of the LHC-associated POTS/IST phenotype, genotype and transcriptional profile, including immunologic and multi-omic analysis of persistent immune activation and dysregulation. The study will also explore and identify potential endotheliopathy and abnormalities of the clotting cascade.
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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/10.1101/2023.04.25.23289110v1" target="_blank">Comparative Cohort Study of Post-Acute Covid-19 Infection with a Nested, Randomized Controlled Trial of Ivabradine for Those With Postural Orthostatic Tachycardia Syndrome (The COVIVA Study)</a>
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</div></li>
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<li><strong>Surveillance of Vermont wildlife in 2021-2022 reveals no detected SARS-CoV-2 viral RNA</strong> -
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<div>
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Previous studies have documented natural infections of SARS-CoV-2 in various domestic and wild animals. More recently, studies have been published noting the susceptibility of members of the Cervidae family, and infections in both wild and captive cervid populations. In this study, we investigated the presence of SARS-CoV-2 in mammalian wildlife within the state of Vermont. 739 nasal or throat samples were collected from wildlife throughout the state during the 2021 and 2022 harvest season. Data was collected from red and gray foxes (Vulpes vulples and Urocyon cineroargentus, respectively), fishers (Martes pennati), river otters (Lutra canadensis), coyotes (Canis lantrans), bobcats (Lynx rufus rufus), black bears (Ursus americanus), and white-tailed deer (Odocoileus virginianus). Samples were tested for the presence of SARS-CoV-2 via quantitative RT-qPCR using the CDC N1/N2 primer set and/or the WHO-E gene primer set. Our results indicate that no sampled wildlife were positive for SARS-CoV-2. This finding is surprising, given that most published North America studies have found SARS-CoV-2 within their deer populations. The absence of SARS-CoV-2 RNA in populations sampled here may provide insights in to the various environmental and anthropogenic factors that reduce spillover and spread in North American’s wildlife populations.
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</div>
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.25.538264v1" target="_blank">Surveillance of Vermont wildlife in 2021-2022 reveals no detected SARS-CoV-2 viral RNA</a>
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</div></li>
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<li><strong>Intranasal VLP-RBD vaccine adjuvanted with BECC470 confers immunity against Delta SARS-CoV-2 challenge in K18-hACE2-mice</strong> -
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As the COVID-19 pandemic transitions to endemic, seasonal boosters are a plausible reality across the globe. We hypothesize that intranasal vaccines can provide better protection against asymptomatic infections and more transmissible variants of SARS-CoV-2. To formulate a protective intranasal vaccine, we utilized a VLP-based platform. Hepatitis B surface antigen-based virus like particles (VLP) linked with receptor binding domain (RBD) antigen were paired with the TLR4-based agonist adjuvant, BECC 470. K18-hACE2 mice were primed and boosted at four-week intervals with either VLP-RBD-BECC or mRNA-1273. Both VLP-RBD-BECC and mRNA-1273 vaccination resulted in production of RBD-specific IgA antibodies in serum. RBD-specific IgA was also detected in the nasal wash and lung supernatants and were highest in VLP-RBD-BECC vaccinated mice. Interestingly, VLP-RBD-BECC vaccinated mice showed slightly lower levels of pre-challenge IgG responses, decreased RBD-ACE2 binding inhibition, and lower neutralizing activity in vitro than mRNA-1273 vaccinated mice. Both VLP-RBD-BECC and mRNA-1273 vaccinated mice were protected against challenge with a lethal dose of Delta variant SARS-CoV-2. Both vaccines limited viral replication and viral RNA burden in the lungs of mice. CXCL10 is a biomarker of severe SARS-CoV-2 infection and we observed both vaccines limited expression of serum and lung CXCL10. Strikingly, VLP-RBD-BECC when administered intranasally, limited lung inflammation at early timepoints that mRNA-1273 vaccination did not. VLP-RBD-BECC immunization elicited antibodies that do recognize SARS-CoV-2 Omicron variant. However, VLP-RBD-BECC immunized mice were protected from Omicron challenge with low viral burden. Conversely, mRNA-1273 immunized mice had low to no detectable virus in the lungs at day 2. Together, these data suggest that VLP-based vaccines paired with BECC adjuvant can be used to induce protective mucosal and systemic responses against SARS-CoV-2.
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</div>
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.25.538294v1" target="_blank">Intranasal VLP-RBD vaccine adjuvanted with BECC470 confers immunity against Delta SARS-CoV-2 challenge in K18-hACE2-mice</a>
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</div></li>
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<li><strong>Remote Aerosol SARS-CoV-2 Transmission from Clinical COVID Patients to Rodent Sentinels</strong> -
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We performed studies investigating the feasibility of human to animal (H2A) model system to test whether patient generated respiratory bioaerosols hold infective capacity when traversing long distance airborne transport within the built environment. South African patients, clinically confirmed by facemask sampling to be exhaling SARS-CoV-2 genomic sequence, were recruited and housed for multiple days in a clinical ward with a uniquely designed building ventilation system continuously channeling exhaust airflow to individual microisolator animal caging units located proximal but segregated from clinic space (University of Pretoria AIR facility).
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🖺 Full Text HTML: <a href="https://osf.io/cre2w/" target="_blank">Remote Aerosol SARS-CoV-2 Transmission from Clinical COVID Patients to Rodent Sentinels</a>
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</div></li>
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<li><strong>Conventional and Bayesian workflows for clinical prediction modelling of severe Covid-19 outcomes based on clinical biomarker test results: LabMarCS: Laboratory Markers of COVID-19 Severity - Bristol Cohort</strong> -
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We describe several regression models to predict severe outcomes in COVID-19 and challenges present in complex observational medical data. We demonstrate best practices for data curation, cross-validated statistical modelling, and variable selection emphasizing recent Bayesian methods. The study follows a retrospective observational cohort design using multicentre records across National Health Service (NHS) trusts in southwest England, UK. Participants included hospitalised adult patients positive for SARS-CoV 2 during March to October 2020, totalling 843 patients (mean age 71, 45% female, 32% died or needed ICU stay), split into training (n=590) and validation groups (n=253). Models were fit to predict severe outcomes (ICU admission or death within 28-days of admission to hospital for COVID-19, or a positive PCR result if already admitted) using demographic data and initial results from 30 biomarker tests collected within 3 days of admission or testing positive if already admitted. Cross-validation results showed standard logistic regression had an internal validation median AUC of 0.74 (95% Interval [0.62,0.83]), and external validation AUC of 0.68 [0.61, 0.71]; a Bayesian logistic regression (with horseshoe prior) internal AUC of 0.79 [0.71, 0.87], and external AUC of 0.70 [0.68, 0.71]. Variable selection performed using Bayesian predictive projection determined a four variable model using Age, Urea, Prothrombin time and Neutrophil-Lymphocyte ratio, with a median internal AUC of 0.79 [0.78, 0.80], and external AUC of 0.67 [0.65, 0.69]. We illustrate best-practices protocol for conventional and Bayesian prediction modelling on complex clinical data and reiterate the predictive value of previously identified biomarkers for COVID-19 severity assessment.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.16.22279985v4" target="_blank">Conventional and Bayesian workflows for clinical prediction modelling of severe Covid-19 outcomes based on clinical biomarker test results: LabMarCS: Laboratory Markers of COVID-19 Severity - Bristol Cohort</a>
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<li><strong>Genomic epidemiology reveals the dominance of Hennepin County in transmission of SARS-CoV-2 in Minnesota from 2020-2022</strong> -
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SARS-CoV-2 has had an unprecedented impact on human health and highlights the need for genomic epidemiology studies to increase our understanding of virus evolution and spread, and to inform policy decisions. We sequenced viral genomes from over 22,000 patient samples tested at Mayo Clinic Laboratories between 2020-2022 and use Bayesian phylodynamics to describe county and regional spread in Minnesota. The earliest introduction into Minnesota was to Hennepin County from a domestic source around January 22, 2020; six weeks before the first confirmed case in the state. This led to the virus spreading to Northern Minnesota, and eventually, the rest of the state. International introductions were most abundant in Hennepin (home to the Minneapolis/St. Paul International (MSP) airport) totaling 45 (out of 107) over the two-year period. Southern Minnesota counties were most common for domestic introductions with 19 (out of 64), potentially driven by bordering states such as Iowa and Wisconsin as well as Illinois which is nearby. Hennepin also was, by far, the most dominant source of in-state transmissions to other Minnesota locations (n=772) over the two-year period. We also analyzed the diversity of the location source of SARS-CoV-2 viruses in each county and noted the timing of state-wide policies as well as trends in clinical cases. Neither the number of clinical cases or major policy decisions, such as the end of the lockdown period in 2020 or the end of all restrictions in 2021, appeared to have impact on virus diversity across each individual county.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.24.22277978v3" target="_blank">Genomic epidemiology reveals the dominance of Hennepin County in transmission of SARS-CoV-2 in Minnesota from 2020-2022</a>
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<li><strong>Variability in excess deaths across countries with different vulnerability during 2020-2023</strong> -
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Importance: Excess deaths provide estimates of total impact of major crises, such as the COVID-19 pandemic. Objective: To evaluate excess deaths trajectories during 2020-2023 across countries with accurate death registration and population age structure data; and to assess how excess death patterns and trajectories correlate with economic indicators of vulnerability overall and in different age strata. Methods: Data were used from the Human Mortality Database on 34 countries. Excess deaths were calculated for 2020-2023 (to 2/26/2023) using 2017-2019 as baseline reference, with weekly expected death calculations and adjustment for 5 age strata. Countries were divided into less and more vulnerable; the latter had per capita nominal GDT<$30,000, Gini>0.35 for income inequality and/or at least 2.5% of their population living in poverty. Results: Excess deaths (as proportion of expected deaths, p% ) were strongly inversely correlated with per capita GDP (r=-0.61), strongly correlated with proportion living in poverty (r=0.65) and modestly correlated with income inequality (r=0.42). The 17 less vulnerable countries had 201,471 excess deaths versus 2,005,380 among the 17 more vulnerable countries. The USA would have had 1.50 million fewer deaths if it had the performance of Sweden, 1.13 million fewer deaths if it had the performance of Finland, and 0.93 million fewer deaths if it had the performance of France. Excess deaths started deviating in the two groups after the first wave when correlational patterns with the 3 economic indicators also started to emerge. Between-country heterogeneity diminished over time within each of the two groups. Less vulnerable countries had mean p%=-0.4% and 0.9% in 0-64 and >65 year-old strata while more vulnerable countries had mean p%=8.3% and 9.0%, respectively. Certain countries performed substantially worse (USA, Canada, Chile, UK) or better (France, Poland, Slovenia) in the non-elderly than in the elderly. Usually lower death rates were seen in children 0-14 years old during 2020-2023 versus pre-pandemic years. Conclusion: While the pandemic hit some countries earlier than others, country vulnerability dominated eventually the cumulative impact. Half of the analyzed countries witnessed no substantial excess deaths versus pre-pandemic levels, while the other half suffered major death tolls.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.24.23289066v1" target="_blank">Variability in excess deaths across countries with different vulnerability during 2020-2023</a>
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<li><strong>Estimation of Near-kink Reproduction Numbers During the Emergent Variants of the COVID-19 Pandemic: Log-quadratic and Forward-imputation Approach</strong> -
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Background: Sketching the major portraits of the COVID-19 epidemic when variants of the pathogen emerge is critical to inform the dynamics of disease transmission, reproduction (i.e., the average counts of individuals of secondary infections generated by an index individual infected by the virus) strength of the pathogen, and countermeasure strategies. Multiple approaches, including log-linear, EpiEstim (an R package generally utilized to estimate the evolution traits of epidemics), and near-log-linear techniques, have been exploited to evaluate the principal parameters such as basic and effective reproduction numbers of an epidemic outbreak. Objective: This study focuses on the kink corner (i.e., sharp alternation of direction of the transmission curve) presenting differentiated log-quadratic traits where more infectious variants of viruses emerge at the diminishing transmission phase of an infectious disease. Methods: A novel log-quadratic trending framework was proposed to project potentially unidentified cases (i.e., forward imputing approximately one week ahead) of COVID-19 around the kink, where the transmission of the pandemic initially lowered and accelerated subsequently, and exercised with the updated framework of classic EpiEstim and Log-linear model. I first compared the performance near the kink using the proposed technique versus the two traditional models taking into account a variety of levels of transmissibility, data distribution (Weibull, Gamma, and Lognormal distributions), and reporting rates (0.2, 0.4, 0.6, 0.8 and 1.0 respectively). Thereafter I utilized the revised framework on the outbreak data of four settings including Bulgaria, Japan, Poland, and South Korea from June to August 2022. Results: The proposed framework reduced the estimation bias versus traditional EpiEstim and log-linear methods near the kink. The coverage estimates of 95% confidence intervals improved. The proposed forward-imputation method implied generally a consistent ascending trend of effective reproduction number estimation applying to a precipitous transition from diminishing to diverging scenarios versus the irregular zigzagging outcomes in classic methods when more contagious variants of the virus were present in the absence of effective vaccines. Conclusions: The log-quadratic correction accounting for transmissibility, data distribution, reporting rates, sliding windows, and generation intervals improved the basic and effective reproduction numbers estimation at the kink corner versus the classic EpiEstim and log-linear models by refined amendment of curve fitting. This is of concern when essentially the fundamental transmission traits of a pandemic alter expeditiously and countermeasures are needed at the earlier variant phases of the transiting climax with the advancement of the pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.24.23289029v1" target="_blank">Estimation of Near-kink Reproduction Numbers During the Emergent Variants of the COVID-19 Pandemic: Log-quadratic and Forward-imputation Approach</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</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>Efficacy and Safety of Nirmatrelvir/Ritonavir for Treating Omicron Variant of COVID-19</strong> - <b>Condition</b>: Omicron Variant of COVID-19<br/><b>Intervention</b>: Drug: Nirmatrelvir/Ritonavir<br/><b>Sponsor</b>: Xiangao Jiang<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 of mRNA-1283.222 Injection Compared With mRNA-1273.222 Injection in Participants ≥12 Years of Age to Prevent COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: mRNA-1283.222; Biological: mRNA-1273.222<br/><b>Sponsor</b>: ModernaTX, 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>Evaluation of the RD-X19 Treatment Device in Individuals With Mild COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Device: RD-X19; Device: Sham<br/><b>Sponsor</b>: EmitBio 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>Postoperative Sugammadex After COVID-19</strong> - <b>Conditions</b>: General Anesthesia; COVID-19<br/><b>Interventions</b>: Drug: Sugammadex Sodium; Drug: neostigmine 50µg/kg + glycopyrollate 0.01mg/kg<br/><b>Sponsor</b>: Korea University Ansan Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study to Determine the Safety and Effectiveness of Azeliragon in the Treatment of Patients Hospitalized for Coronavirus Disease 2019 (COVID-19)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Azeliragon; Drug: Placebo<br/><b>Sponsor</b>: Salim S. Hayek<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>To Evaluate the Safety and Efficacy of Meplazumab in Treatment of Post-COVID-19</strong> - <b>Condition</b>: Post-COVID-19<br/><b>Interventions</b>: Biological: Meplazumab for injection; Other: Normal saline<br/><b>Sponsor</b>: Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cognitive-behavioral Therapy for Mental Disorder in COVID-19 Survivors</strong> - <b>Condition</b>: Post Acute COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: mindfulness-based stress reduction (MBSR) and cognitive behavioral therapy (CBT)<br/><b>Sponsor</b>: Azienda Socio Sanitaria Territoriale di Lecco<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of Lactobacillus Paracasei PS23 for Patients With Post-COVID-19 Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Dietary Supplement: PS23 heat-treated<br/><b>Sponsors</b>: Mackay Memorial Hospital; Bened Biomedical Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Coping and Resilience Intervention for Adolescents</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Behavioral: Coping and Resilience Intervention for Adolescents; Other: Printing materials of Coping and Resilience Intervention for Adolescents<br/><b>Sponsor</b>: Taipei Medical University<br/><b>Enrolling by invitation</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>Effectiveness of Modified Diaphragmatic Training for Gastroesophageal Reflux Disease Post Covid-19</strong> - <b>Conditions</b>: GERD; Post COVID-19 Condition; Diaphragm Issues<br/><b>Intervention</b>: Other: Diaphragmatic Training<br/><b>Sponsor</b>: Indonesia 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>Effect of Telerehabilitation Practice in Long COVID-19 Patients</strong> - <b>Conditions</b>: Long COVID-19; Long COVID; Post COVID-19 Condition; Post-COVID-19 Syndrome; Post-COVID Syndrome<br/><b>Interventions</b>: Behavioral: Telerehabilitation; Behavioral: Standard rehabilitation care<br/><b>Sponsor</b>: Indonesia 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>The Safety, Tolerability and Pharmacokinetics Study of RAY1216 in Healthy Adult Participants</strong> - <b>Condition</b>: COVID-19 (Coronavirus Disease 2019)<br/><b>Interventions</b>: Drug: RAY1216 dose 1; Drug: RAY1216 dose 2; Drug: RAY1216 dose 3; Drug: RAY1216 dose 4 &ritonavir Drug: RAY1216 dose 5; Drug: RAY1216 dose 6; Drug: RAY1216 dose 7; Drug: RAY1216 dose 8; Drug: RAY1216 dose 9; Drug: RAY1216 dose 10<br/><b>Sponsor</b>: Guangdong Raynovent Biotech Co., Ltd<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>Computerized Training of Attention and Working Memory in Post COVID-19 Patients With Cognitive Complaints</strong> - <b>Conditions</b>: COVID-19; Cognitive Impairment; Cognition Disorder; Memory Disorders; Attention Deficit; Memory Impairment; Memory Loss; Attention Impaired<br/><b>Intervention</b>: Device: RehaCom<br/><b>Sponsor</b>: Erasmus Medical Center<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>Strategies and Treatments for Respiratory Infections &Amp; Viral Emergencies (STRIVE): Immune Modulation Strategy Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: abatacept infusion; Drug: Placebo group<br/><b>Sponsor</b>: University of Minnesota<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of Silmitasertib (CX-4945) in Healthy Subject</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: CX-4945<br/><b>Sponsor</b>: Senhwa Biosciences, Inc.<br/><b>Active, not 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>Regulatory approval pathway for COVID-19 vaccine in USA, Europe and India</strong> - The coronavirus disease-2019 (COVID-19) outbreak has confused everyone, including healthcare experts, physicians and frontline workers. Monoclonal antibodies, anticoagulants and immunomodulatory therapy were initially used to treat COVID-19. However, they can only inhibit the virus from replicating, which is not enough to provide a lasting cure. As each month passes, a growing number of companies are working on vaccinations that will aid in the development of resistance against the corona virus….</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>Discovery of Highly Potent Small Molecule Pan-Coronavirus Fusion Inhibitors</strong> - The unprecedented pandemic of COVID-19, caused by a novel coronavirus, SARS-CoV-2, and its highly transmissible variants, led to massive human suffering, death, and economic devastation worldwide. Recently, antibody-evasive SARS-CoV-2 subvariants, BQ and XBB, have been reported. Therefore, the continued development of novel drugs with pan-coronavirus inhibition is critical to treat and prevent infection of COVID-19 and any new pandemics that may emerge. We report the discovery of several highly…</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 Flavonoid Cyanidin Shows Immunomodulatory and Broad-Spectrum Antiviral Properties, Including SARS-CoV-2</strong> - New antiviral treatments are needed to deal with the unpredictable emergence of viruses. Furthermore, vaccines and antivirals are only available for just a few viral infections, and antiviral drug resistance is an increasing concern. Cyanidin (a natural product also called A18), a key flavonoid that is present in red berries and other fruits, attenuates the development of several diseases, through its anti-inflammatory effects. Regarding its mechanism of action, A18 was identified as an IL-17A…</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 Plant-Made Human Recombinant ACE2 against COVID-19 in a Golden Syrian Hamster Model</strong> - Coronavirus disease 2019 (COVID-19) is a novel infectious respiratory disease caused by SARS-CoV-2. We evaluated the efficacy of a plant-based human recombinant angiotensin-converting enzyme 2 (hrACE2) and hrACE2-foldon (hrACE2-Fd) protein against COVID-19. In addition, we analyzed the antiviral activity of hrACE2 and hrACE2-Fd against SARS-CoV-2 using real-time reverse-transcription PCR and plaque assays. The therapeutic efficacy was detected using the Golden Syrian hamster model infected with…</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 Rab1B Impairs Trafficking and Maturation of SARS-CoV-2 Spike Protein</strong> - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) utilizes cellular trafficking pathways to process its structural proteins and move them to the site of assembly. Nevertheless, the exact process of assembly and subcellular trafficking of SARS-CoV-2 proteins remains largely unknown. Here, we have identified and characterized Rab1B as an important host factor for the trafficking and maturation of the spike protein (S) after synthesis at the endoplasmic reticulum (ER). Using confocal…</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>Perspectives Associated with Human Papillomavirus Vaccination in Adults: A Qualitative Study</strong> - CONCLUSION: Both intrinsic and extrinsic factors play a role in influencing HPV vaccine uptake, and such considerations can guide efforts to improve the odds of HPV vaccination in working-age adults.</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>An Oral Galectin Inhibitor in COVID-19-A Phase II Randomized Controlled Trial</strong> - CONCLUSION: PL-M is safe and effective for clinical use in reducing viral loads and promoting rapid viral clearance in COVID-19 patients by inhibiting SARS-CoV-2 entry into cells through the inhibition of Gal-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>Electrosprayed Mesenchymal Stromal Cell Extracellular Matrix Nanoparticles Accelerate Cellular Wound Healing and Reduce Gram-Negative Bacterial Growth</strong> - Treatments for acute respiratory distress syndrome are still unavailable, and the prevalence of the disease has only increased due to the COVID-19 pandemic. Mechanical ventilation regimens are still utilized to support declining lung function but also contribute to lung damage and increase the risk for bacterial infection. The anti-inflammatory and pro-regenerative abilities of mesenchymal stromal cells (MSCs) have shown to be a promising therapy for ARDS. We propose to utilize the regenerative…</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>Establishment of an Antiplasmodial Vaccine Based on PfRH5-Encoding RNA Replicons Stabilized by Cationic Liposomes</strong> - CONCLUSION: Intradermal delivery of cationic lipid-encapsulated samRNA constructs is a feasible approach for developing future malaria vaccines.</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>Autochthonous Peruvian Natural Plants as Potential SARS-CoV-2 M<sup>pro</sup> Main Protease Inhibitors</strong> - Over 750 million cases of COVID-19, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), have been reported since the onset of the global outbreak. The need for effective treatments has spurred intensive research for therapeutic agents based on pharmaceutical repositioning or natural products. In light of prior studies asserting the bioactivity of natural compounds of the autochthonous Peruvian flora, the present study focuses on the identification SARS-CoV-2 M^(pro) main…</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>Heparin, Low Molecular Weight Heparin, and Non-Anticoagulant Derivatives for the Treatment of Inflammatory Lung Disease</strong> - Unfractionated heparin has multiple pharmacological activities beyond anticoagulation. These anti-inflammatory, anti-microbial, and mucoactive activities are shared in part by low molecular weight and non-anticoagulant heparin derivatives. Anti-inflammatory activities include inhibition of chemokine activity and cytokine synthesis, inhibitory effects on the mechanisms of adhesion and diapedesis involved in neutrophil recruitment, inhibition of heparanase activity, inhibition of the proteases 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>Recent Advances in Anti-Tuberculosis Drug Discovery Based on Hydrazide-Hydrazone and Thiadiazole Derivatives Targeting InhA</strong> - Tuberculosis is an extremely serious problem of global public health. Its incidence is worsened by the presence of multidrug-resistant (MDR) strains of Mycobacterium tuberculosis. More serious forms of drug resistance have been observed in recent years. Therefore, the discovery and/or synthesis of new potent and less toxic anti-tubercular compounds is very critical, especially having in mind the consequences and the delays in treatment caused by the COVID-19 pandemic. Enoyl-acyl carrier protein…</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>Current Update on Role of Hesperidin in Inflammatory Lung Diseases: Chemistry, Pharmacology, and Drug Delivery Approaches</strong> - Inflammation is a common feature of many respiratory diseases, such as pneumonia, asthma, pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), lung cancer, acute lung injury, and COVID-19. Flavonoids have demonstrated their anti-inflammatory and antioxidant effects by influencing inflammation at different stages and majorly impacting several respiratory diseases’ onset and development. According to current studies, hesperidin, one of the most abundant polyphenols, can inhibit…</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>Azido-Ceramides, a Tool to Analyse SARS-CoV-2 Replication and Inhibition-SARS-CoV-2 Is Inhibited by Ceramides</strong> - Recently, we have shown that C6-ceramides efficiently suppress viral replication by trapping the virus in lysosomes. Here, we use antiviral assays to evaluate a synthetic ceramide derivative α-NH2-ω-N3-C6-ceramide (AKS461) and to confirm the biological activity of C6-ceramides inhibiting SARS-CoV-2. Click-labeling with a fluorophore demonstrated that AKS461 accumulates in lysosomes. Previously, it has been shown that suppression of SARS-CoV-2 replication can be cell-type specific. Thus, AKS461…</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>Mycolactone: A Broad Spectrum Multitarget Antiviral Active in the Picomolar Range for COVID-19 Prevention and Cure</strong> - We have previously shown computationally that Mycolactone (MLN), a toxin produced by Mycobacterium ulcerans, strongly binds to Munc18b and other proteins, presumably blocking degranulation and exocytosis of blood platelets and mast cells. We investigated the effect of MLN on endocytosis using similar approaches, and it bound strongly to the N-terminal of the clathrin protein and a novel SARS-CoV-2 fusion protein. Experimentally, we found 100% inhibition up to 60 nM and 84% average inhibition at…</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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