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<title>23 June, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>U.S. state-level COVID-19 transmission insights from a mechanistic mobility-incidence model</strong> -
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Background: Throughout the COVID-19 pandemic, human mobility has played a central role in shaping disease transmission. In this study, we develop a mechanistic model to calculate disease incidence from commercially-available US mobility data over the course of 2020. We use it to study, at the US state level, the lag between infection and case report. We examine the evolution of per-contact transmission probability, and its dependence on mean air temperature. Finally, we evaluate the potential of the model to produce short-term incidence forecasts from mobility data. Methods: We develop a mechanistic model that relates COVID-19 incidence to time series contact index (CCI) data collected by mobility data vendor Cuebiq. From this, we perform maximum-likelihood estimates of the transmission probability per CCI event. Finally, we retrospectively conduct forecasts from multiple dates in 2020 forward. Findings: Across US states, we find a median lag of 19 days between transmission and case report. We find that the median transmission probability from May onward was about 20% lower than it was during March and April. We find a moderate, statistically significant negative correlation between mean state temperature and transmission probability, r = -.57, N = 49, p = 2e-5. We conclude that for short-range forecasting, CCI data would likely have performed best overall during the first few months of the pandemic. Interpredation: Our results are consistent with associations between colder temperatures and stronger COVID-19 burden reported in previous studies, and suggest that changes in the per-contact transmission probability play an important role. Our model displays good potential as a short-range (2 to 3 week) forecasting tool during the early stages of a future pandemic, before non-pharmaceutical interventions (NPIs) that modify per-contact transmission probability, principally face masks, come into widespread use. Hence, future development should also incorporate time series data of NPI use.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.21.22276712v1" target="_blank">U.S. state-level COVID-19 transmission insights from a mechanistic mobility-incidence model</a>
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</div></li>
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<li><strong>Natural course of post COVID-19 condition and implications for trial design and outcome selection: A population-based longitudinal cohort study</strong> -
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<b>Background:</b> Evidence from population-based studies on the longer-term natural course of post COVID-19 condition is limited, but crucial for informing patients and healthcare providers and for effectively designing clinical trials. <b>Objectives:</b> To evaluate longer-term symptoms and health outcomes within a cohort of SARS-CoV-2 infected individuals. <b>Design:</b> Population-based, longitudinal cohort. <b>Setting:</b> General population, Canton of Zurich, Switzerland. <b>Patients:</b> 1543 adults with confirmed SARS-CoV-2 infection and 628 adults without infection. <b>Measurements:</b> Changes in self-reported health status over time, factors associated with persistence of non-recovery, and prevalence and excess risk of symptoms at 6 and 12 months post-infection compared to non-infected individuals. <b>Results:</b> 25% of SARS-CoV-2 infected individuals did not recover by 6 months. Of those, 67% and 58% also did not recover at 12 and 18 months after infection, respectively. Hospitalization for acute COVID-19, pre-existing fatigue and pain or discomfort, and presence of specific systemic, cardiovascular, or musculoskeletal symptoms at 6 months were associated with persistent non-recovery. Symptom prevalence was higher among infected individuals compared to non-infected individuals at 6 months (adjusted risk difference (aRD)=17%) and 12 months (aRD=20%). aRDs for individual symptoms ranged from 2% to 12%, with the highest excess risks observed for altered taste or smell, post-exertional malaise, fatigue, and reduced concentration and memory. <b>Limitations:</b> We relied on self-reported assessments and did not assess the effects of vaccination or infection with emerging variants of concern. <b>Conclusion:</b> These findings emphasize the need for effective interventions to reduce the burden of post COVID-19 condition. They further demonstrate the importance of using multiple outcome measures and of considering the expected rates of natural recovery and heterogenous patient trajectories in the design and interpretation of clinical trials.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.22.22276746v1" target="_blank">Natural course of post COVID-19 condition and implications for trial design and outcome selection: A population-based longitudinal cohort study</a>
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</div></li>
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<li><strong>THE MAJOR ROLE OF JUNCTIONAL DIVERSITY IN THE HORSE ANTIBODY REPERTOIRE</strong> -
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<div>
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The sequencing of the antibody repertoire (Rep-seq) revolutionized the diversity of antigen B cell receptor studies, allowing deep and quantitative analysis to decipher the role of adaptive immunity in health and disease. Particularly, horse (Equus caballus) polyclonal antibodies have been produced and used since the century XIX to treat and prophylaxis of diphtheria, tuberculosis, tetanus, pneumonia, and, more recently, COVID-19. However, our knowledge about the horse B cell receptors repertories is minimal. We present a deep horse antibody heavy chain repertoire (IGH) characterization of non-immunized horses using HTS technology. In this study, we obtained a mean of 248,169 unique IgM clones and 66,141 unique IgG clones from four domestic adult horses. Rarefaction analysis showed sequence coverage was between 52 and 82% in IgM and IgG isotypes. We observed that besides horses antibody can use all of the functional IGHV genes, around 80% of their antibodies use only three IGHV gene segments, and around 55% use only one IGHJ gene segment. This limited VJ diversity seems to be compensated by the junctional diversity of these antibodies. We observed that the junctional diversity in horses antibodies is highly frequent, present in more than 90% of horse antibodies. Besides this, the length of this region seems to be higher in horse antibodies than in other species. N1 and N2 nucleotides addition range from 0 to 111 nucleotides. In addition, around 45% of the antibody clones have more than ten nucleotides in both N1 and N2 junction regions. This diversity mechanism may be one of the most important in providing variability to the equine antibody repertoire. This study provides new insights regarding horse antibody composition, diversity generation, and particularities compared to other species, such as the frequency and length of N nucleotide addition. This study also points out the urgent need to better characterize TdT in horses and in other species to better understand antibody repertoire characteristics.
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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/10.1101/2022.06.20.496904v1" target="_blank">THE MAJOR ROLE OF JUNCTIONAL DIVERSITY IN THE HORSE ANTIBODY REPERTOIRE</a>
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</div></li>
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<li><strong>Increased levels of circulating neurotoxic metabolites in patients with mild Covid19</strong> -
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<div>
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SARS-CoV-2 corona virus causes a multi-faceted and poorly defined clinical and pathological phenotype involving hyperinflammation, cytokine release. And long-term cognitive deficits, with an undefined neuropathological mechanism. Inflammation increases the activity of the kynurenine pathway, which is linked to neurodegenerative and psychiatric disorders. We sought to determine whether the kynurenine pathway is impacted in patients with mild COVID-19, leading to elevated neurotoxic metabolites in blood, and whether such changes are associated with pro-inflammatory cytokines. Serum samples were taken from 150 patients and analyzed by ELISA and ultra-high performance liquid chromatography (UHPLC). The data were analyzed using multiple linear regression models adjusted for age and sex. We found increased levels of kynurenine, quinolinic acid and 3-hydroxykynurenine in serum from patients with mild COVID-19, together with increased levels of IL-6, ICAM-1, VCAM-1 and neopterin. The levels of neurotoxic metabolites were significantly associated with key inflammatory cytokines including IL-6 and TNF. The COVID-19 risk-factor hypertension was associated with the highest levels of neurotoxic metabolites in plasma. These neuroactive metabolites could be part of the pathological mechanisms underlying cognitive impairment during and post-COVID and should be explored as potential biomarkers for long-COVID symptoms.
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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/10.1101/2022.06.22.497189v1" target="_blank">Increased levels of circulating neurotoxic metabolites in patients with mild Covid19</a>
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</div></li>
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<li><strong>Within-host evolutionary dynamics and tissue compartmentalization during acute SARS-CoV-2 infection</strong> -
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<div>
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The global evolution of SARS-CoV-2 depends in part upon the evolutionary dynamics within individual hosts with varying immune histories. To characterize the within-host evolution of acute SARS-CoV-2 infection, we deep sequenced saliva and nasal samples collected daily from immune and unvaccinated individuals early during infection. We show that longitudinal sampling facilitates high-confidence genetic variant detection and reveals evolutionary dynamics missed by less-frequent sampling strategies. Within-host dynamics in both naive and immune individuals appeared largely stochastic; however, we identified clear mutational hotspots within the viral genome, consistent with selection and differing between naive and immune individuals. In rare cases, minor genetic variants emerged to frequencies sufficient for forward transmission. Finally, we detected significant genetic compartmentalization of virus between saliva and nasal swab sample sites in many individuals. Altogether, these data provide a high-resolution profile of within-host SARS-CoV-2 evolutionary dynamics.
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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/10.1101/2022.06.21.497047v1" target="_blank">Within-host evolutionary dynamics and tissue compartmentalization during acute SARS-CoV-2 infection</a>
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</div></li>
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<li><strong>Mutational insights among the structural proteins of SARS-CoV-2: frequencies and evolutionary trends in American countries</strong> -
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<div>
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a role in the mortality of more than 6 million people worldwide. This virus owns the genome, which contains four structural proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N). The occurrence of structural mutations can induce the emergence of new variants. Depending on the mutations, the variants may display different patterns of infectivity, mortality, and sensitivity toward drugs and vaccines. In this study, we analyzed samples of amino-acid sequences (AASs) for structural proteins from the coronavirus 2019 (COVID-19) declaration as a pandemic to April 2022 among American countries. The analysis process included considering mutations’ frequencies, locations, and evolutionary trends utilizing sequence alignment to the reference sequence. In the following, the results were compared with the same analyses among the samples of the entire world. Results displayed that despite samples of North America and international countries that own the region of 508 to 635 with the highest mutation frequency among S AASs, the region with the same characteristic was concluded as 1 to 127 in South America. Besides, the most frequent mutations in S, E, M, and N proteins from North America and worldwide samples were concluded as D614G, T9I, I82T, and R203M. In comparison, R203K was the first frequent mutation in N samples in South America. Widely comparing mutations between North America and South America and between the Americas and the world can help scientists introduce better drug and vaccine development strategies.
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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/10.1101/2022.06.22.497134v1" target="_blank">Mutational insights among the structural proteins of SARS-CoV-2: frequencies and evolutionary trends in American countries</a>
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<li><strong>Fc-modified SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models.</strong> -
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The use of therapeutic neutralizing antibodies against SARS-CoV-2 infection has been highly effective. However, there remain few practical antibodies against viruses that are acquiring mutations. In this study, we created 494 monoclonal antibodies from COVID-19-convalescent patients, and identified antibodies that exhibited comparable neutralizing ability to clinically used antibodies in the neutralization assay using pseudovirus and authentic virus including variants of concerns. These antibodies have different profiles against various mutations, which were confirmed by cell-based assay and cryo-electron microscopy. To prevent antibody-dependent enhancement, N297A modification was introduced, and showed a reduction of lung viral RNAs by therapeutic administration in a hamster model. In addition, an antibody cocktail consisting of three antibodies was also administered therapeutically to a macaque model, which resulted in reduced viral titers of swabs and lungs and reduced lung tissue damage scores. These results showed that our antibodies have sufficient antiviral activity as therapeutic candidates.
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</div>
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.21.496751v1" target="_blank">Fc-modified SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models.</a>
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</div></li>
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<li><strong>Leveraging serology testing to identify children at risk for post-acute sequelae of SARS-CoV-2 infection: An EHR-based cohort study from the RECOVER program</strong> -
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The impact of post-acute sequelae of SARS-CoV-2 infection (PASC) in children is underrecognized. We developed an EHR-based algorithm across eight pediatric institutions to identify children with COVID-19 based on serology testing from 3/2020 through 4/2022 who had not been identified by PCR. Overall, serology tests were used 100-fold less than PCR. Seroprevalence of IgG anti-nucleocapsid antibodies remained stable, while rates of positive IgG anti-spike antibodies increased in teenagers after COVID-19 vaccine approval. Through data harmonization and after excluding 1,410 serology test results that may have been influenced by vaccines, we identified 2,714 children that were COVID-19 positive exclusively by serology. These patients were frequently tested as inpatients (24% vs. 2%), had chronic conditions more frequently (37% vs 24%), and a MIS-C diagnosis (23% vs. <1%) compared with PCR-positive children. Identification of children that could have been paucisymptomatic, not tested, or missed is critical to define the burden of PASC in children.
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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/10.1101/2022.06.20.22276645v1" target="_blank">Leveraging serology testing to identify children at risk for post-acute sequelae of SARS-CoV-2 infection: An EHR-based cohort study from the RECOVER program</a>
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<li><strong>VirPool: Model-Based Estimation of SARS-CoV-2 Variant Proportions in Wastewater Samples</strong> -
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Background: The genomes of SARS-CoV-2 are classified into variants, some of which are monitored as variants of concern (e.g. the delta variant B.1.617.2 or omicron variant B.1.1.529). Proportions of these variants in a population are typically estimated by large-scale sequencing of individual patient samples. Sequencing a mixture of SARS-CoV-2 RNA molecules from wastewater provides a cost-effective alternative, but requires methods for estimating variant proportions in a mixed sample. Results: We propose a new method based on a probabilistic model of sequencing reads, capturing sequence diversity present within individual variants, as well as sequencing errors. The algorithm is implemented in an open source Python program called VirPool. We evaluated the accuracy of VirPool on several simulated and real sequencing data sets from both Illumina and nanopore sequencing platforms, including wastewater samples from Austria and France monitoring the onset of alpha and delta variants. Conclusions: VirPool is a versatile tool for wastewater and other mixed-sample analysis that can handle both short- and long-read sequencing data. Our approach does not require pre-selection of characteristic mutations for variant profiles, it is able to use the entire length of reads instead of just the most informative positions, and can also capture haplotype dependencies within a single read.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.21.22276717v1" target="_blank">VirPool: Model-Based Estimation of SARS-CoV-2 Variant Proportions in Wastewater Samples</a>
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<li><strong>COVID-19 rebound after Paxlovid and Molnupiravir during January-June 2022</strong> -
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Abstract Importance Recent case reports document that some patients who were treated with Paxlovid experienced rebound COVID-19 infections and symptoms 2 to 8 days after completing a 5-day course of Paxlovid. The Centers for Disease Control and Prevention (CDC) has recently issued a Health Alert Network Health Advisory to update the public on the potential for COVID-19 rebound after Paxlovid treatments. However, the rates of COVID-19 rebound in a real-world population or whether rebound is unique to Paxlovid remains unknown. Objectives To examine the rates and relative risks of COVID-19 rebound in patients treated with Paxlovid or with Molnupiravir and to compare characteristics of patients who experienced COVID-19 rebound to those who did not. Design, Setting, and Participants Retrospective cohort study of electronic health records (EHRs) of 92 million patients from a multicenter and nationwide database in the US. The study population comprised 13,644 patients age 18 years or older who contracted COVID-19 between 1/1/2022-6/8/2022 and were treated with Paxlovid (n =11,270) or with Molnupiravir (n =2,374) within 5 days of their COVID-19 infection. Exposures Paxlovid or Molnupiravir. Main Outcomes and Measures Three types of COVID-19 rebound outcomes (COVID-19 infections, COVID-19 related symptoms, and hospitalizations) were examined. Hazard ratios and 95% confidence interval (CI) of 7-day and 30-day risk for COVID-19 rebound between patients treated with Paxlovid and patients treated with Molnupiravir were calculated before and after propensity-score matching. Results The 7-day and 30-day COVID-19 rebound rates after Paxlovid treatment were 3.53% and 5.40% for COVID-19 infection, 2.31% and 5.87% for COVID-19 symptoms, and 0.44% and 0.77% for hospitalizations. The 7-day and 30-day COVID-19 rebound rates after Molnupiravir treatment were 5.86% and 8.59% for COVID-19 infection, 3.75% and 8.21% for COVID-19 symptoms, and 0.84% and 1.39% for hospitalizations. After propensity-score matching, there were no significant differences in COVID-19 rebound risks between Paxlovid and Molnupiravir: infection (HR 0.90, 95% CI: 0.73-1.11), COVID-19 symptoms (HR: 1.03, 95% CI: 0.83-1.27), or hospitalizations (HR: 0.92, 95% CI: 0.56-1.55). Patients with COVID-19 rebound had significantly higher prevalence of underlying medical conditions than those without. Conclusions and Relevance COVID-19 rebound occurred both after Paxlovid and Molnupiravir, especially in patients with underlying medical conditions. This indicates that COVID-19 rebound is not unique to Paxlovid and the risks were similar for Paxlovid and Molnupiravir. For both drugs the rates of COVID-19 rebound increased with time after treatments. Our results call for continuous surveillance of COVID-19 rebound after Paxlovid and Molnupiravir treatments. Studies are necessary to determine the mechanisms underlying COVID-19 rebounds and to test dosing and duration regimes that might prevent such rebounds in vulnerable patients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.21.22276724v1" target="_blank">COVID-19 rebound after Paxlovid and Molnupiravir during January-June 2022</a>
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<li><strong>Multiple cohort study of hospitalized SARS-CoV-2 in-host infection dynamics: parameter estimates, sensitivity and the eclipse phase profile</strong> -
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Within-host SARS-CoV-2 modelling studies have been published throughout the COVID-19 pandemic. These studies contain highly variable numbers of individuals and capture varying timescales of pathogen dynamics; some studies capture the time of disease onset, the peak viral load and subsequent heterogeneity in clearance dynamics across individuals, while others capture late-time post-peak dynamics. In this study, we curate multiple previously published SARS-CoV-2 viral load data sets, fit these data with a consistent modelling approach, and estimate the variability of in-host parameters including the basic reproduction number, R0. We find that fitted dynamics can be highly variable across data sets, and highly variable within data sets, particularly when key components of the dynamic trajectories (e.g. peak viral load) are not represented in the data. Further, we investigated the role of the eclipse phase time distribution in fitting SARS-CoV-2 viral load data. By varying the shape parameter of an Erlang distribution, we demonstrate that models with either no eclipse phase, or with an exponentially-distributed eclipse phase, offer significantly worse fits to these data, whereas models with less dispersion around the mean eclipse time (shape parameter two or more) offered the best fits to the available data.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.20.22276662v1" target="_blank">Multiple cohort study of hospitalized SARS-CoV-2 in-host infection dynamics: parameter estimates, sensitivity and the eclipse phase profile</a>
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<li><strong>Persistence of SARS-CoV-2 omicron variant in children and utility of rapid antigen testing as an indicator of culturable virus</strong> -
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We screened 65 longitudinally-collected nasal swab samples from 31 children aged 0-16 years who were positive for SARS-CoV-2 omicron BA.1. By day 7 after onset of symptoms 48% of children remained positive by rapid antigen test. In a sample subset we found 100% correlation between antigen test results and virus culture.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.21.22276668v1" target="_blank">Persistence of SARS-CoV-2 omicron variant in children and utility of rapid antigen testing as an indicator of culturable virus</a>
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<li><strong>Impact of COVID-19 vaccination on long COVID: a systematic review and meta-analysis</strong> -
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Abstract Background: The impact of COVID-19 vaccination on preventing or treating long COVID is unclear. We aim to assess the impact of COVID vaccinations administered (i) before and (ii) after acute COVID-19, including vaccination after long COVID diagnosis, on the rates or symptoms of long COVID. Methods: We searched PubMed, Embase, Cochrane COVID-19 trials, and Europe PMC for preprints from 1 Jan 2020 to 16 Feb 2022. We included trials, cohort, and case control studies reporting on long COVID cases and symptoms with vaccine administration both before and after COVID-19 diagnosis as well as after long COVID diagnosis. Risk of bias was assessed using ROBINS-I. Results: We screened 356 articles and found no trials, but 6 observational studies from 3 countries (USA, UK, France) that reported on 442,601 patients. The most common long COVID symptoms studied include fatigue, cough, loss of smell, shortness of breath, loss of taste, headache, muscle ache, trouble sleeping, difficulty concentrating, worry or anxiety, and memory loss or confusion. Four studies reported data on vaccination before SARS-CoV-2 infection, of which three showed statistically significant reduction in long COVID: the odds ratio of developing long COVID with one dose of vaccine ranged between OR 0.22 to 1.03; with two doses OR 0.51 to 1; and with any dose OR 0.85 to 1.01. Three studies reported on post-infection vaccination with odds ratios between 0.38 to 0.91. The high heterogeneity between studies precluded any meaningful meta-analysis. Studies failed to adjust for potential confounders such as other protective behaviours, and missing data, thus increasing the risk of bias, and decreasing the certainty of evidence to low. Discussion: Current studies suggest that COVID-19 vaccinations may have protective and therapeutic effects on long COVID. However, more robust comparative observational studies and trials are urgently needed to clearly determine effectiveness of vaccines in prevention and treatment of long COVID.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.20.22276621v1" target="_blank">Impact of COVID-19 vaccination on long COVID: a systematic review and meta-analysis</a>
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<li><strong>Effects of the COVID-19 pandemic on self-reported 12-month pneumococcal vaccination series completion rates in Canada: An interrupted time-series analysis</strong> -
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Background: Routine childhood vaccination improves health and prevents morbidity and mortality from vaccination preventable diseases. There are indications that the COVID19 pandemic has negatively impacted vaccination rates globally, but systematic studies on this are still lacking in Canada. This study aims to add knowledge on the effect of the pandemic on pneumococcal vaccination rates of children using self-reported immunization data entered into the CANImmunize digital vaccination tool. Methodology: An interrupted time series analysis was conducted on aggregated monthly enrollment of children on the platform (2016 to 2021) and their pneumococcal immunization series completion rates (2016 to 2020). Predicted trends before and after the onset of the COVID19 related restriction (March 1, 2020) were compared by means of an Autoregressive Integrated Moving Average (ARIMA). Results: Pandemic restrictions were associated with changes in self reported pneumococcal immunization rates amongst the users of the CANImmunize platform. The monthly enrollment of children on the platform decreased by 1177.52 records (95% CI: -1865.47, -489.57), with a continued decrease of 80.84 records each month. Self-reported pneumococcal immunization series completion rates had an immediate increase of 14.57% (95% CI 4.64, 24.51) followed by a decrease of -3.54% each month. Conclusion: The onset of the COVID19 related restrictions impacted enrollment of children in the CANImmunize digital immunization platform, and an overall decrease in self-reported pneumococcal immunization series completion rates. Our findings support that efforts to increase catch-up immunization campaigns so that children who could not get scheduled immunization during the pandemic are not missed.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.21.22276720v1" target="_blank">Effects of the COVID-19 pandemic on self-reported 12-month pneumococcal vaccination series completion rates in Canada: An interrupted time-series analysis</a>
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<li><strong>The impact of lag time to cancer diagnosis and treatment on clinical outcomes prior to the COVID-19 pandemic: a scoping review of systematic reviews and meta-analyses</strong> -
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Background: The COVID-19 pandemic has disrupted cancer care, raising concerns regarding the impact of wait time, or lag time, on clinical outcomes. We aimed to contextualize pandemic-related lag times by mapping pre-pandemic evidence from systematic reviews and/or meta-analyses on the association between lag time to cancer diagnosis and treatment with mortality- and morbidity-related outcomes. Methods: We systematically searched MEDLINE, EMBASE, Web of Science, and Cochrane Library of Systematic Reviews for reviews published prior to the pandemic (1 January 2010-31 December 2019). We extracted data on methodological characteristics, lag time interval start and endpoints, qualitative findings from systematic reviews, and pooled risk estimates of mortality- (i.e., overall survival) and morbidity- (i.e., local regional control) related outcomes from meta-analyses. We categorized lag times according to milestones across the cancer care continuum and summarized outcomes by cancer site and lag time interval. Results: We identified 9,032 records through database searches, of which 29 were eligible. We classified 33 unique types of lag time intervals across 10 cancer sites, of which breast, colorectal, head and neck, and ovarian cancers were investigated most. Two systematic reviews investigating lag time to diagnosis reported contradictory findings regarding survival outcomes among pediatric patients with Ewing9s sarcomas or central nervous system tumours. Comparable risk estimates of mortality were found for lag time intervals from surgery to adjuvant chemotherapy for breast, colorectal, and ovarian cancers. Risk estimates of pathologic complete response indicated an optimal time window of 7-8 weeks for neoadjuvant chemotherapy completion prior to surgery for rectal cancers. In comparing methods across meta-analyses on the same cancer sites, lag times, and outcomes, we identified critical variations in lag time research design. Conclusions: Our review highlighted measured associations between lag time and cancer-related outcomes and identified the need for a standardized methodological approach in areas such as lag time definitions and accounting for the waiting-time paradox. Prioritization of lag time research is integral for revised cancer care guidelines under pandemic contingency and assessing the pandemic9s long-term effect on patients with cancer.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.21.22276569v1" target="_blank">The impact of lag time to cancer diagnosis and treatment on clinical outcomes prior to the COVID-19 pandemic: a scoping review of systematic reviews and meta-analyses</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>COVID-19 Algorithm Treatment at Home</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Recommended treatment schedule; Drug: Usual care<br/><b>Sponsor</b>: Mario Negri Institute for Pharmacological Research<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>Immunosuppression and COVID-19 Boosters</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: diphtheria and tetanus toxoids (adsorbed) vaccine; Biological: COVID-19 vaccine<br/><b>Sponsors</b>: Kirby Institute; Seqirus Pty Ltd, Australia; Medical Research Future Fund (MRFF)<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>Discussing COVID-19 Vaccines in Private Facebook Groups</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Gist messages on COVID-19 vaccination; Behavioral: COVID-19 vaccine information<br/><b>Sponsor</b>: George Washington 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>Epidemiological Monitoring of COVID-19 Patients Hospitalized on Reunion Island</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: telephone interview 24 months after hospitalization for Covid-19<br/><b>Sponsor</b>: Centre Hospitalier Universitaire de la Réunion<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>Immunogenicity and Safety Study of Booster Vaccine With the COVID-19 Vaccine (Vero Cell), Inactivated, Omicron Strain</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: COVID-19 Vaccine (Vero Cell), Inactivated, Omicron Strain<br/><b>Sponsor</b>: Sinovac Biotech (Hong Kong) Limited<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>Home-Based Exercise Tele-Rehabilitation After COVID-19</strong> - <b>Condition</b>: Post SARS-CoV2 (COVID-19)<br/><b>Intervention</b>: Other: Tele-exercise<br/><b>Sponsors</b>: VA Office of Research and Development; Baltimore Veterans Affairs Medical Center; Salem Veterans Affairs 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>Plerixafor in Acute Respiratory Distress Syndrome Related to COVID-19 (Phase IIb)</strong> - <b>Conditions</b>: COVID-19 Acute Respiratory Distress Syndrome; COVID-19<br/><b>Interventions</b>: Drug: Plerixafor 20 MG/ML [Mozobil]; Other: Placebo<br/><b>Sponsor</b>: 4Living Biotech<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>Calcitriol Supplementation in COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Vitamin D Deficiency<br/><b>Intervention</b>: Drug: Calcitriol<br/><b>Sponsor</b>: RenJi 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>Olfactory Training in COVID-19 Associated Loss of Smell</strong> - <b>Conditions</b>: COVID-19; Hyposmia<br/><b>Intervention</b>: Device: Sniffin’ sticks Duftquartett<br/><b>Sponsor</b>: Medical University Innsbruck<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>Psychological Impact of Medical Evacuations on Families of Patients Admitted to Intensive Care Unit for Severe COVID-19</strong> - <b>Conditions</b>: COVID-19; Stress Disorders, Post-Traumatic<br/><b>Interventions</b>: Other: Revised Impact of Event Scale; Other: Hospital Anxiety and Depression scale; Other: 36-Item Short Form Survey; Other: satisfaction survey; Other: semi-directed interview with trusted person on the general experience of the patient’s medical evacuation; Other: semi-directed interview with trusted person on the general experience of hospitalization in intensive care<br/><b>Sponsor</b>: Centre Hospitalier Metropole Savoie<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 COVID-19 on Platelet Mitochondrial Bioenergetic, Antioxidants and Oxidative Stress in Infertile Men.</strong> - <b>Conditions</b>: Infertility, Male; COVID-19<br/><b>Intervention</b>: Other: diagnostic test and sperm analysis<br/><b>Sponsors</b>: Comenius University; GYN-FIV<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of Telerehabilitative Aerobic and Relaxation Exercises Patients With Type 2 Diabetes With and Without COVID-19</strong> - <b>Conditions</b>: COVID-19; Type 2 Diabetes Mellitus<br/><b>Intervention</b>: Other: Aerobic and Relaxation Exercises<br/><b>Sponsor</b>: Bozyaka Training and Research Hospital<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate Immunogenicity and Safety of MVC-COV1901 Vaccine Compared With AZD1222</strong> - <b>Condition</b>: COVID-19 Vaccine<br/><b>Interventions</b>: Biological: MVC-COV1901; Biological: AZD1222<br/><b>Sponsor</b>: Medigen Vaccine Biologics Corp.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Vaccine Uptake Trial</strong> - <b>Conditions</b>: Vaccination Refusal; COVID-19<br/><b>Interventions</b>: Other: Short Message Service (SMS) + Website Link Strategy; Other: Phone Call with Peer Strategy<br/><b>Sponsor</b>: Washington University School of Medicine<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>Cardiovascular Autonomic and Immune Mechanism of Post COVID-19 Tachycardia Syndrome</strong> - <b>Conditions</b>: Post-acute COVID-19 Syndrome; Postural Tachycardia Syndrome (POTS); Long COVID; SARS CoV 2 Infection<br/><b>Interventions</b>: Diagnostic Test: Determine the inflammatory and immune profile of post-COVID-19 POTS patients; Diagnostic Test: Measurement of PNS activity by HRV (Heart rate Variation); Diagnostic Test: Autonomic Symptoms assessment<br/><b>Sponsors</b>: Vanderbilt University Medical Center; American Heart Association<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification and characterization of the anti-SARS-CoV-2 activity of cationic amphiphilic steroidal compounds</strong> - The ongoing COVID-19 pandemic caused a significant loss of human lives and a worldwide decline in quality of life. Treatment of COVID-19 patients is challenging, and specific treatments to reduce COVID-19 aggravation and mortality are still necessary. Here, we describe the discovery of a novel class of epiandrosterone steroidal compounds with cationic amphiphilic properties that present antiviral activity against SARS-CoV-2 in the low micromolar range. Compounds were identified in screening…</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>Comparative evaluation of authorized drugs for treating Covid-19 patients</strong> - CONCLUSION: All authorized drugs are effective in inhibiting viral replication for most SARS-CoV-2 variants. Therefore, along with vaccines, these drugs might potentially aid in fighting the Covid-19 pandemic.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of SARS-CoV-2 spike protein entry using biologically modified polyacrylonitrile nanofibers: <em>in vitro</em> study towards specific antiviral masks</strong> - With the increase of the contagiousness rates of Coronavirus disease (COVID-19), new strategies are needed to halt virus spread. Blocking virus entry by capturing its spike (S) protein is one of the effective approaches that could help in eliminating or reducing transmission rate of viruses. Herein, we aim to develop a nanofiber-based filter for protective face masks, composed of polyacrylonitrile (PAN) nanofibers (NFs)-loaded with Angiotensin Converting Enzyme-2 (ACE-2) for capturing the spike…</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>Antiviral efficacy of selective estrogen receptor modulators against SARS-CoV-2 infection in vitro and in vivo reveals bazedoxifene acetate as an entry inhibitor</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the seventh member of the coronavirus family that can infect humans. Recently, more contagious and pathogenic variants of SARS-CoV-2 have been continuously emerging. Clinical candidates with high efficacy and ready availability are still in urgent need. To identify potent anti-SARS-CoV-2 repurposing drugs, we evaluated the antiviral efficacy of 18 selective estrogen receptor modulators (SERMs) against SARS-CoV-2 infection. Six SERMs…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 coagulopathy - what should we treat?</strong> - NEW FINDINGS: What is the topic of this review? Overview of the coagulation abnormalities, including elevated D-dimers widely reported with COVID-19, often labelled as COVID coagulopathy. What advances does it highlight? The review highlights the changes in bronchoalveolar haemostasis due to apoptosis of alveolar cells, which contributes to acute lung injury and acute respiratory distress syndrome; the pathophysiological mechanisms, including endothelial dysfunction and damage responsible for…</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>Exploring the potential mechanism of emetine against coronavirus disease 2019 combined with lung adenocarcinoma: bioinformatics and molecular simulation analyses</strong> - CONCLUSIONS: This study found that emetine may inhibit the entry and replication of SARS-CoV-2 and enhance tumor immunity by bounding to DDP4 and Mpro.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 virus NSP14 Impairs NRF2/HMOX1 activation by targeting Sirtuin 1</strong> - Most deaths from the COVID-19 pandemic are due to acute respiratory distress syndrome (ARDS)-related respiratory failure. Cytokine storms and oxidative stress are the major players in ARDS development during respiratory virus infections. However, it is still unknown how oxidative stress is regulated by viral and host factors in response to SARS-CoV-2 infection. Here, we found that activation of NRF2/HMOX1 significantly suppressed SARS-CoV-2 replication in multiple cell types by producing 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>Quercetin and luteolin are single-digit micromolar inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global health pandemic. Among the viral proteins, RNA-dependent RNA polymerase (RdRp) is responsible for viral genome replication and has emerged as one of the most promising targets for pharmacological intervention against SARS-CoV-2. To this end, we experimentally tested luteolin and quercetin for their ability to inhibit the RdRp enzyme. These two compounds are ancestors of flavonoid natural compounds known for…</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>Modulating Fingolimod (FTY720) Anti-SARS-CoV-2 Activity Using a PLGA-Based Drug Delivery System</strong> - COVID-19 has resulted in more than 490 million people being infected worldwide, with over 6 million deaths by April 05th, 2022. Even though the development of safe vaccine options is an important step to reduce viral transmission and disease progression, COVID-19 cases will continue to occur, and for those cases, efficient treatment remains to be developed. Here, a drug repurposing strategy using nanotechnology is explored to develop a therapy for COVID-19 treatment. Nanoparticles (NPs) based on…</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>Bergamottin, a bioactive component of bergamot, inhibits SARS-CoV-2 infection in golden Syrian hamsters</strong> - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused an ongoing pandemic, coronavirus disease-2019 (COVID-19), which has become a major global public health event. Antiviral compounds remain the predominant means of treating COVID-19. Here, we reported that bergamottin, a furanocoumarin originally found in bergamot, exhibited inhibitory activity against SARS-CoV-2 in vitro, ex vivo, and in vivo. Bergamottin interfered with multiple stages of virus life cycles, specifically…</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: The Journey from Parenteral Agent to Nasal Delivery</strong> - Although the worldwide usage of direct oral anticoagulants has continuously increased over the past decade, heparin remains an important weapon in the current arsenal of anticoagulant drugs. Parenteral heparin administration (i.e., either intravenously or subcutaneously) has represented for decades the only possible route for generating a significant anticoagulant effect, although being notoriously associated with some important drawbacks such as discomfort and risk of low compliance, thus…</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 effect of various compounds on the COVID mechanisms, from chemical to molecular aspects</strong> - The novel coronavirus that caused COVID-19 pandemic is SARS-CoV-2. Although various vaccines are currently being used to prevent the disease’s severe consequences, there is still a need for medications for those who become infected. The SARS-CoV-2 has a variety of proteins that have been studied extensively since the virus’s advent. In this review article, we looked at chemical to molecular aspects of the various structures studied that have pharmaceutical activity and attempted to find a link…</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>Computational repurposing approach for targeting the critical spike mutations in B.1.617.2 (delta), AY.1 (delta plus) and C.37 (lambda) SARS-CoV-2 variants using exhaustive structure-based virtual screening, molecular dynamic simulations and MM-PBSA methods</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the contagious coronavirus disease 2019 (COVID-19) which was first identified in Wuhan, China, in December 2019. Around the world, many researchers focused their research on identifying inhibitors against the druggable SARS-CoV-2 targets. The reported genomic mutations have a direct effect on the receptor-binding domain (RBD), which interacts with host angiotensin-converting enzyme 2 (ACE-2) for viral cell…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Nucleocapsid mutations in SARS-CoV-2 augment replication and pathogenesis</strong> - While SARS-CoV-2 continues to adapt for human infection and transmission, genetic variation outside of the spike gene remains largely unexplored. This study investigates a highly variable region at residues 203-205 in the SARS-CoV-2 nucleocapsid protein. Recreating a mutation found in the alpha and omicron variants in an early pandemic (WA-1) background, we find that the R203K+G204R mutation is sufficient to enhance replication, fitness, and pathogenesis of SARS-CoV-2. The R203K+G204R mutant…</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 Bioactivities of Phycocyanobilin from Spirulina</strong> - Phycocyanobilin (PCB) is a linear open-chain tetrapyrrole chromophore that captures and senses light and a variety of biological activities, such as anti-oxidation, anti-cancer, and anti-inflammatory. In this paper, the biological activities of PCB are reviewed, and the related mechanism of PCB and its latest application in disease treatment are introduced. PCB can resist oxidation by scavenging free radicals, inhibiting the activity of nicotinamide adenine dinucleotide phosphate (NADPH)…</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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