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<title>02 September, 2021</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 data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The SARS-CoV-2 spike (S) and the orthoreovirus p15 cause neuronal and glial fusion</strong> -
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Numerous enveloped viruses use specialized surface molecules called fusogens to enter host cells. During virus replication, these fusogens decorate the host cells membrane enabling them the ability to fuse with neighboring cells, forming syncytia that the viruses use to propagate while evading the immune system. Many of these viruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infect the brain and may cause serious neurological symptoms through mechanisms which remain poorly understood. Here we show that expression of either the SARS-CoV-2 spike</div></li>
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<li>protein or p15 protein from the baboon orthoreovirus is sufficient to induce fusion between interconnected neurons, as well as between neurons and glial cells. This phenomenon is observed across species, from nematodes to mammals, including human embryonic stem cells-derived neurons and brain organoids. We show that fusion events are progressive, can occur between distant neurites, and lead to the formation of multicellular syncytia. Finally, we reveal that in addition to intracellular molecules, fusion events allow diffusion and movement of large organelles such as mitochondria between fused neurons. Our results provide important mechanistic insights into how SARS-CoV-2 and other viruses could affect the nervous system circuitries causing neurological symptoms.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.09.01.458544v1" target="_blank">The SARS-CoV-2 spike (S) and the orthoreovirus p15 cause neuronal and glial fusion</a>
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<li><strong>Tiled-ClickSeq for targeted sequencing of complete coronavirus genomes with simultaneous capture of RNA recombination and minority variants</strong> -
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High-throughput genomics of SARS-CoV-2 is essential to characterize virus evolution and to identify adaptations that affect pathogenicity or transmission. While single-nucleotide variations (SNVs) are commonly considered as driving virus adaption, RNA recombination events that delete or insert nucleic acid sequences are also critical. Whole genome targeting sequencing of SARS-CoV-2 is typically achieved using pairs of primers to generate cDNA amplicons suitable for Next-Generation Sequencing (NGS). However, paired-primer approaches impose constraints on where primers can be designed, how many amplicons are synthesized and requires multiple PCR reactions with non-overlapping primer pools. This imparts sensitivity to underlying SNVs and fails to resolve RNA recombination junctions that are not flanked by primer pairs. To address these limitations, we have designed an approach called ‘Tiled-ClickSeq’, which uses hundreds of tiled-primers spaced evenly along the virus genome in a single reverse-transcription reaction. The other end of the cDNA amplicon is generated by azido-nucleotides that stochastically terminate cDNA synthesis, removing the need for a paired-primer. A sequencing adaptor containing a Unique Molecular Identifier (UMI) is appended to the cDNA fragment using click-chemistry and a PCR reaction generates a final NGS library. Tiled-ClickSeq provides complete genome coverage, including the 5’UTR, at high depth and specificity to the virus on both Illumina and Nanopore NGS platforms. Here, we analyze multiple SARS-CoV-2 isolates and clinical samples to simultaneously characterize minority variants, sub-genomic mRNAs (sgmRNAs), structural variants (SVs) and D-RNAs. Tiled-ClickSeq therefore provides a convenient and robust platform for SARS-CoV-2 genomics that captures the full range of RNA species in a single, simple assay.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.03.10.434828v2" target="_blank">Tiled-ClickSeq for targeted sequencing of complete coronavirus genomes with simultaneous capture of RNA recombination and minority variants</a>
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</div></li>
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<li><strong>Codon usage pattern reveals SARS-CoV-2 as a monomorphic pathogen of hybrid origin with role of silent mutations in rapid evolutionary success</strong> -
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Viruses are dependent on the host tRNA pool, and an optimum codon usage pattern (CUP) is the driving force in its evolution. Systematic analysis of CUP of the coding sequences (CDS) of representative major pangolin lineages A and B of SARS-CoV-2 indicate a single transmission event of a codon-optimized virus from its source into humans. Here, no direct congruence could be detected in CUP of all CDS of SARS-CoV-2 with the non-human natural SARS viruses further reiterating its novelty. Several CDS show similar CUP with bat or pangolin, while others have distinct CUP pointing towards a possible hybrid nature of the virus. At the same time, phylogenetic diversity suggests the role of even silent mutations in its success by adapting to host tRNA pool. However, genomes of SARS-CoV-2 from primary infections are required to investigate the origins amongst the competing natural or lab leak theories.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.10.12.335521v2" target="_blank">Codon usage pattern reveals SARS-CoV-2 as a monomorphic pathogen of hybrid origin with role of silent mutations in rapid evolutionary success</a>
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</div></li>
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<li><strong>Absence of severe COVID-19 in patients with clonal mast cells activation disorders: effective anti-SARS-CoV-2 immune response.</strong> -
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Mast cells are key actors of innate immunity and Th2 adaptive immune response which counterbalance Th1 response, critical for anti-viral immunity. Clonal Mast Cells Activation Disorders (cMCADs) such as mastocytosis and clonal mast cells activation syndrome are characterized by an abnormal mast cells accumulation and/or activation. No data have been published on the anti-viral immune response of patients with cMCADs. The aims of the study were to collected, in a comprehensive way, outcomes of cMCADs patients who experienced a biologically-proven COVID-19 and to characterize both anti-endemic coronaviruses and specific anti-SARS-CoV-2 immune responses in these patients. Clinical follow-up and outcome data were collected prospectively for one year within the French rare disease network CEREMAST encompassing patients from all over the country. Anti-SARS-CoV-2 and anti-endemic coronaviruses specific T-cells were assessed with an enzyme-linked immunospot assay (EliSpot) and anti-SARS-CoV-2 humoral response with dosage of circulating levels of specific IgG, IgA and neutralizing antibodies. Overall, 32 cMCADs patients were identified. None of them required non- invasive or mechanical ventilation; two patients were hospitalized to receive oxygen and steroid therapy. In 21 patients, a characterization of the SARS-CoV-2-specific immune response has been performed. A majority of patients showed a high proportion of circulating SARS-CoV-2-specific interferon (IFN)-{gamma} producing T-cells and high levels of anti-Spike IgG antibodies with neutralizing activity. In addition, no defects in anti-endemic coronaviruses responses were found in patients with cMCADs compared to non-cMCADs controls. Patients with cMCADs frequently showed a spontaneous IFN-{gamma} T-cell production in absence of any stimulation that correlated with circulating basal tryptase levels, a marker of mast cells burden. These findings underscore that patients with cMCADs might be not at risk of severe COVID-19 and the spontaneous IFN-{gamma} production might explain this observation.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.09.01.458516v1" target="_blank">Absence of severe COVID-19 in patients with clonal mast cells activation disorders: effective anti-SARS- CoV-2 immune response.</a>
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<li><strong>Early post-infection treatment of SARS-CoV-2 infected macaques with human convalescent plasma with high neutralizing activity reduces lung inflammation</strong> -
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Early in the SARS-CoV-2 pandemic, there was a high level of optimism based on observational studies and small controlled trials that treating hospitalized patients with convalescent plasma from COVID-19 survivors (CCP) would be an important immunotherapy. However, as more data from controlled trials became available, the results became disappointing, with at best moderate evidence of efficacy when CCP with high titers of neutralizing antibodies was used early in infection. To better understand the potential therapeutic efficacy of CCP, and to further validate SARS-CoV-2 infection of macaques as a reliable animal model for testing such strategies, we inoculated 12 adult rhesus macaques with SARS-CoV-2 by intratracheal and intranasal routes. One day later, 8 animals were infused with pooled human CCP with a high titer of neutralizing antibodies (RVPN NT50 value of 3,003), while 4 control animals received normal human plasma. Animals were monitored for 7 days. Animals treated with CCP had detectable levels of antiviral antibodies after infusion. In comparison to the control animals, they had similar levels of virus replication in the upper and lower respiratory tract, but had significantly reduced interstitial pneumonia, as measured by comprehensive lung histology. By highlighting strengths and weaknesses, data of this study can help to further optimize nonhuman primate models to provide proof-of-concept of intervention strategies, and guide the future use of convalescent plasma against SARS-CoV-2 and potentially other newly emerging respiratory viruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.09.01.458520v1" target="_blank">Early post-infection treatment of SARS-CoV-2 infected macaques with human convalescent plasma with high neutralizing activity reduces lung inflammation</a>
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<li><strong>Analysis of changes occurring in Codon Positions due to mutations through the cellular automata transition rules</strong> -
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Variation in the nucleotides of a codon may cause variations in the evolutionary patterns of a DNA or amino acid sequence. To address the capability of each position of a codon to have non-synonymous mutations, the concept of degree of mutation has been introduced. The degree of mutation of a particular position of codon defines the number of non- synonymous mutations occurring for the substitution of nucleotides at each position of a codon, when other two positions of that codon remain unaltered.A Cellular Automaton (CA), is used as a tool to model the mutations of any one of the four DNA bases A, C, T and G at a time where the DNA bases correspond to the states of the CA cells. Point mutation (substitution type) of a codon which characterizes changes in the amino acids, have been associated with local transition rules of a CA. Though there can be 443transitions of a4-state CA with3-neighbourhood cells, here it has been possible to represent all possible point mutations of a codon in terms of combinations of 16 local transition functions of the CA. Further these rules are divided into 4classes of equivalence. Also, according to the nature of mutations, the 16 local CA rules of substitutions are classified into 3 sets namely, No Mutation, Transition and Transversion. The experiment has been carried out with three sets of single nucleotide variations (SNVs) of three different viruses but the symptoms of the diseases caused by them are to some extent similar to each other. They are SARS-CoV-1, SARS-CoV-2 and H1N1 Type A viruses. The aim is to understand the impact of nucleotide substitutions at different positions of a codon with respect to a particular disease phenotype.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.08.30.458305v1" target="_blank">Analysis of changes occurring in Codon Positions due to mutations through the cellular automata transition rules</a>
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<li><strong>COVID-eVax, an electroporated plasmid DNA vaccine candidate encoding the SARS-CoV-2 Receptor Binding Domain, elicits protective immune responses in animal models of COVID-19</strong> -
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The COVID-19 pandemic caused by the {beta}-coronavirus SARS-CoV-2 has made the development of safe and effective vaccines a critical global priority. To date, four vaccines have already been approved by European and American authorities for preventing COVID-19 but the development of additional vaccine platforms with improved supply and logistics profiles remains a pressing need. Here we report the preclinical evaluation of a novel COVID-19 vaccine candidate based on the electroporation of engineered, synthetic cDNA encoding a viral antigen in the skeletal muscle, a technology previously utilized for cancer vaccines. We constructed a set of prototype DNA vaccines expressing various forms of the SARS-CoV-2 Spike (S) protein and assessed their immunogenicity in animal models. Among them, COVID-eVax - a DNA plasmid encoding a secreted monomeric form of SARS-CoV-2 S protein RBD - induced the most potent anti-SARS-CoV-2 neutralizing antibody responses (including against the current most common variants of concern) and a robust T cell response. Upon challenge with SARS-CoV-2, immunized K18-hACE2 transgenic mice showed reduced weight loss, improved pulmonary function and significantly lower viral replication in the lungs and brain. COVID-eVax conferred significant protection to ferrets upon SARS-CoV-2 challenge. In summary, this study identifies COVID-eVax as an ideal COVID-19 vaccine candidate suitable for clinical development. Accordingly, a combined phase I-II trial has recently started in Italy.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.06.14.448343v2" target="_blank">COVID-eVax, an electroporated plasmid DNA vaccine candidate encoding the SARS-CoV-2 Receptor Binding Domain, elicits protective immune responses in animal models of COVID-19</a>
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<li><strong>Remdesivir-Ivermectin combination displays synergistic interaction with improved in vitro antiviral activity against SARS-CoV-2</strong> -
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A key element for the prevention and management of COVID-19 is the development of effective therapeutics. Drug combination strategies of repurposed drugs offer several advantages over monotherapies, including the potential to achieve greater efficacy, the potential to increase the therapeutic index of drugs and the potential to reduce the emergence of drug resistance. Here, we report on the in vitro synergistic interaction between two FDA approved drugs, remdesivir and ivermectin resulting in enhanced antiviral activity against SARS-CoV-2. These findings warrant further investigations into the clinical potential of this combination, together with studies to define the underlying mechanism.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.23.424232v2" target="_blank">Remdesivir-Ivermectin combination displays synergistic interaction with improved in vitro antiviral activity against SARS-CoV-2</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pre-existing antibodies targeting a linear epitope on SARS-CoV-2 S2 cross-reacted with commensal gut bacteria and shaped vaccine induced immunity</strong> -
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Pre-existing SARS-CoV-2 cross-reactive antibodies have been detected in both unexposed human and animals. However, the origins of these cross-reactive antibodies and their potential impacts on vaccine efficacy have not been completely clarified. In this study, we demonstrated that the S2 subunit was the predominant target of the pre-existing SARS-CoV-2 spike protein cross-reactive antibodies in both healthy human and naive SPF mice. Through linear epitope mapping, we identified a dominant antibody epitope on the connector domain of S2 (aa1145-aa1162), which could be recognized by antibodies pre-existed in unexposed human and mice. Six monoclonal antibodies against this linear epitope were isolated from naive SPF mice and were proved to cross-react with commensal gut bacteria collected from both human and mouse. Via immunizing mice with a candidate DNA vaccine encoding the full length of SARS-CoV-2 spike protein, we further demonstrated that high levels of pre-existing S2 cross-reactive antibodies did not impair the immunogenicity of the DNA vaccine. On the contrary, mice with high levels of pre-existing antibodies mounted stronger S2 specific binding antibody responses compared to mice with low levels of pre-existing antibodies. In addition, S1 specific T cell and binding antibody responses also tended to be enhanced in mice with high levels of pre-existing antibodies.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.07.13.21260404v4" target="_blank">Pre-existing antibodies targeting a linear epitope on SARS-CoV-2 S2 cross-reacted with commensal gut bacteria and shaped vaccine induced immunity</a>
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<li><strong>Immunological dysfunction persists for 8 months following initial mild-moderate SARS-CoV-2 infection</strong> -
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A proportion of patients surviving acute COVID-infection develop post-COVID syndrome (long COVID) encompassing physical and neuropsychiatric symptoms lasting longer than 12 weeks. Here we studied a prospective cohort of individuals with long COVID compared to age/gender matched subjects without long COVID (from the ADAPT study), unexposed healthy donors and individuals infected with other non-SARS CoV2 human coronaviruses (the ADAPT-C study). We found highly activated innate immune cells and an absence of subsets of un-activated naive T and B cells in peripheral blood of long COVID subjects, that did not reconstitute over time. These activated myeloid cells may contribute to the elevated levels of type I (IFN-b) and III interferon (IFN-L1) that remained persistently high in long COVID subjects at 8 months post- infection. We found positive inter-analyte correlations that consisted of 18 inflammatory cytokines in symptomatic long COVID subjects that was not observed in asymptomatic COVID-19 survivors. A linear classification model was used to exhaustively search through all 20,475 combinations of the 29 analytes measured, that had the strongest association with long COVID and found that the best 4 analytes were: IL-6, IFNg, MCP-1 (CCL2) and VCAM-1. These four inflammatory biomarkers gave an accuracy of 75.9%, and an F1 score of 0.759, and have also previously been associated with acute severe disease. In contrast, plasma ACE2 levels, while elevated in the serum of people previously infected with SARS- CoV-2 were not further elevated in subjects with long COVID symptoms. This work defines immunological parameters associated with long COVID and suggests future opportunities to prevention and treatment.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.06.01.21257759v2" target="_blank">Immunological dysfunction persists for 8 months following initial mild-moderate SARS-CoV-2 infection</a>
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<li><strong>PERCOVID: A Model to Describe COVID Percolation on a Network of Social Relationships</strong> -
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We develop a site-bond percolation model, called PERCOVID, in order to describe the time evolution of COVID epidemics and more generally all epidemics propagating through respiratory tract in human populations. This model is based on a network of social relationships representing interconnected households experiencing governmental non- pharmaceutical interventions. The model successfully accounts for the COVID-19 epidemiological data in metropolitan France from December 2019 up to July 2021. Our model shows the impact of lockdowns and curfews, as well as the influence of the progressive vaccination campaign in order to keep COVID-19 pandemic under the percolation threshold. We illustrate the role played by the social interactions by comparing a typical scenario for the epidemic evolution in France, Germany and Italy during the first wave from January to May 2020. We investigate finally the role played by the alpha and delta variants in the evolution of the epidemic in France till autumn 2021, paying particular attention to the essential role played by the vaccination. Our model predicts that the rise of the epidemic observed in July 2021 will not result in a fourth major epidemic wave in France.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.08.31.21262909v1" target="_blank">PERCOVID: A Model to Describe COVID Percolation on a Network of Social Relationships</a>
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<li><strong>Attitude and Behavior of People Towards Visiting the Hospital During the Pandemic</strong> -
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Introduction: Visiting the hospital is important as a part of check-up in avoiding the major risks of unknown and serious diseases irrespective of any pandemic. Our study aims to understand the attitude and behaviour of common people towards visiting the hospital during COVID-19 pandemic in two major hotspot states of India namely Maharashtra and Karnataka. Methodology: A cross-sectional study was conducted between July-august 2021 among the population of two states. A total of 636 respondents completed the survey and returned electronically. Data were analysed using suitable statistical tools to achieve the objective of the study. Results: 74.8% of the respondents were not ready to visit the hospitals during the COVID-19 pandemic unless the symptoms were serious. On the other hand, 25.2% of the of respondents were willing to go to the hospitals. The top three reasons for the reduction in visits are fear of getting infected in the hospitals by COVID-19 patients (72.6%), fear of stepping out of home (31.1%) and fear of COVID-19 infection by the lab equipment (24.5%). Conclusion: Overall the study revealed that there was a reduction in number of visits to the hospitals for common diseases in people after the pandemic started. But the people were still willing to go to the hospitals if they noticed any major symptoms or symptoms related to COVID-19. Our findings may be useful to develop strategies to address concerns in order to ensure that people do not get any serious illness because of the fear of COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.08.21.21261953v1" target="_blank">Attitude and Behavior of People Towards Visiting the Hospital During the Pandemic</a>
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<li><strong>Health impact and cost of COVID-19 prophylaxis with monoclonal antibodies</strong> -
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Background: The COVID-19 pandemic has led to over 600,000 deaths in the United States and continues to disrupt lives even as effective vaccines are available. We aimed to estimate the impact and health system cost of implementing post-exposure prophylaxis against household exposure to COVID-19 with monoclonal antibodies. Methods: We developed a decision-analytical model analysis of results from a recent randomized controlled trial with complementary data on household demographic structure, vaccine coverage, and COVID-19 confirmed case counts for the representative month of May, 2021. The model population includes individuals of all ages in the United States by sex and race/ethnicity. Results: In a month of similar intensity to May, 2021, in the USA, a monoclonal antibody post-exposure prophylaxis program reaching 50% of exposed unvaccinated household members aged 50+, would avert 1,813 (1,171 - 2,456) symptomatic infections, 526 (343 - 716) hospitalizations, and 83 (56 - 116) deaths. Assuming the unit cost of administering the intervention was US$ 1,264, this program would save the health system US$ 3,055,202 (-14,034,632 - 18,787,692). Conclusions: Currently in the United States, health system and public health actors have an opportunity to improve health and reduce costs through COVID-19 post-exposure prophylaxis with monoclonal antibodies.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.08.31.21262923v1" target="_blank">Health impact and cost of COVID-19 prophylaxis with monoclonal antibodies</a>
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<li><strong>Evaluation of patient experience for a computationally-guided intranasal spray protocol to augment therapeutic penetration</strong> -
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The global respiratory outbreak in the form of COVID-19 has underlined the necessity to devise more effective and reproducible intranasal drug delivery modalities, that would also be user-friendly for adoption compliance. In this study, we have collected evaluation feedback from a cohort of 13 healthy volunteers, who assessed two different nasal spray administration techniques, namely the vertical placement protocol (or, VP), wherein the nozzle is held vertically upright at a shallow insertion depth of 0.5 cm inside the nasal vestibule; and the shallow angle protocol (or, SA), wherein the spray axis is angled at 45 degrees to the vertical, with a vestibular insertion depth of 1.5 cm. The SA protocol is derived from published findings on alternate spray orientations that have been shown to enhance targeted delivery at posterior infection sites, e.g., the ostiomeatal complex and the nasopharynx. All study participants reported that the SA protocol offered a more gentle and soothing delivery experience, with less impact pressure. Additionally, 60% participants opined that the VP technique caused painful irritation. We also tracked the drug transport processes for the two spray techniques in a computed tomography-based nasal reconstruction; the SA protocol marked a distinct improvement in therapeutic penetration when compared to the VP protocol.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.08.31.21262495v1" target="_blank">Evaluation of patient experience for a computationally-guided intranasal spray protocol to augment therapeutic penetration</a>
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<li><strong>COVID-19 personal protective behaviors during mass events: Lessons from observational measures in Wales, UK.</strong> -
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<div>
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Within the context of reopening society in the summer of 2021, as the UK moved away from ’lockdown,’ the Government of Wales piloted the return on organised ‘mass gatherings’ of people at a number of test events. Behavioral observations were made at two of the test events to support this process. The research was particularly interested in four key factors: How (1) context within a venue, (2) environmental design, (3) staffing and social norms, and (4) time across an event, affected personal protective behaviors of social distancing, face covering use, and hand hygiene. Data collection was undertaken by trained observers across the above factors. Findings suggest that adherence of attendees was generally high, but with clear indications that levels were shaped in a systematic way by the environment, situational cues, and the passage of time during the events. Some instances of large-scale non-adherence to personal protective behaviors were documented. Overall, there were three main situations where behavioral adherence broke down, under conditions where: (1) staff were not present; (2) there was a lack of environmental signalling (including physical interventions or communications); and (3) later into the events when circumstances were less constrained and individuals appeared less cognitively vigilant. Behavioral observations at events can add precision and identify critical risk situations where/when extra effort is required. The findings suggest a liberal paternal approach whereby state authorities, health authorities and other key organisations can help nudge individuals towards COVID-safe behaviors. Finally, an individual’s intentions are not always matched by their actions, and so behavioral insights can help identify situations and contexts where people are most likely to require additional support to ensure COVID-19 personal protective behaviors are followed and hence protecting themselves and others.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/8jsr3/" target="_blank">COVID-19 personal protective behaviors during mass events: Lessons from observational measures in Wales, UK.</a>
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</div></li>
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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>High-dose Intravenous Vitamin C (HDIVC) as Adjuvant Therapy in Critical Patients With Positive COVID-19. A Pilot Randomized Controlled Dose-comparison Trial.</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: High doses of intravenous vitamin C; Drug: Dextrose 500 mL<br/><b>Sponsor</b>: Hugo Galindo<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Developing and Testing a COVID-19 Vaccination Acceptance Intervention</strong> - <b>Condition</b>: COVID-19 Vaccination<br/><b>Intervention</b>: Behavioral: Moving to COVID-19 Vaccine Acceptance Intervention<br/><b>Sponsors</b>: VA Office of Research and Development; VA Bedford Healthcare System<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>Andrographis Paniculata vs Boesenbergia Rotunda vs Control in Asymptomatic COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Andrographis Paniculata; Drug: Boesenbergia; Other: Standard supportive treatment<br/><b>Sponsors</b>: Mahidol University; Ministry of Health, Thailand<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>Enhancing COVID Rehabilitation With Technology</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Behavioral: NexJ Connected Wellness; Other: Usual Care<br/><b>Sponsors</b>: University of Ottawa; Canadian Institutes of Health Research (CIHR); Ottawa Hospital Research Institute<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase I/II Clinical Trial of Recombinant COVID-19 Vaccine (Sf9 Cells) in Children and Adolescents</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant COVID-19 vaccine (Sf9 cells); Other: Placebo control<br/><b>Sponsors</b>: WestVac Biopharma Co., Ltd.; West China 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>Treatment of Covid-19 With a Herbal Compound, Xagrotin</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Combination Product: Xagrotin<br/><b>Sponsors</b>: <br/>
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Biomad AS; Directorate of health of Sulaimani, Iraq -KRG<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>Philippine Trial to Determine Efficacy and Safety of Favipiravir for COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Combination Product: Favipiravir + Standard of Care; Procedure: Standard of Care<br/><b>Sponsors</b>: University of the Philippines; Department of Health, Philippines<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 Safety and Immunogenicity of a Novel Vaccine for Prevention of Covid-19 in Adults Previously Immunized</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Biological: A vaccine composed of a recombinant S1 antigen<br/><b>Sponsors</b>: Hospital do Coracao; Farmacore Biotecnologia Ltda<br/><b>Withdrawn</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>Phase 3 Clinical Study Evaluating Nitric Oxide Nasal Spray (NONS) Efficacy To Treat and Prevent the Exacerbation of Infection in Individuals With Documented Asymptomatic or Mild COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: to be given as a treatment<br/><b>Sponsor</b>: <br/>
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Salmaniya Medical Complex<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>Comparison of Detection of SARS-CoV2 (COVID-19) Between Nasopharyngeal Swab Specimens and Those Obtained by Salivary Sputum</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Diagnostic Test: Salivary test for COVID19<br/><b>Sponsor</b>: Centre Hospitalier de Cayenne<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>Menstrual Blood Stem Cells in Severe Covid-19</strong> - <b>Conditions</b>: Covid19; Cytokine Storm<br/><b>Interventions</b>: Biological: Allogeneic human menstrual blood stem cells secretome; Other: Intravenous saline injection<br/><b>Sponsors</b>: Avicenna Research Institute; Tehran University of Medical Sciences<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>Public Health Emergency: SOLIDARITY TRIAL Philippines</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Remdesivir; Drug: Hydroxychloroquine; Drug: Lopinavir / Ritonavir; Drug: Interferon beta-1a; Drug: Acalabrutinib<br/><b>Sponsor</b>: <br/>
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University of the Philippines<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>Tazemetostat for the Treatment of Moderate to Severe COVID-19 Infection</strong> - <b>Conditions</b>: COVID-19 Acute Respiratory Distress Syndrome; Cytokine Release Syndrome<br/><b>Intervention</b>: Drug: Tazemetostat<br/><b>Sponsor</b>: Ciprian Gheorghe<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>Osteopathy and Physiotherapy Compared to Physiotherapy Alone on Fatigue and Functional Status in Long COVID</strong> - <b>Conditions</b>: Covid19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Other: Osteopathic Manipulative Treatment in addition to Physiotherapy; Other: Physiotherapy<br/><b>Sponsors</b>: <br/>
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Centro Universitário Augusto Motta; Instituto Brasileiro de Osteopatia<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>Sexual Functions and Covid-19</strong> - <b>Conditions</b>: Covid19; Sexual Behavior<br/><b>Intervention</b>: Behavioral: Women sexual dysfunctions were screened using Female Sexual Functioning Index (FSFI)<br/><b>Sponsor</b>: <br/>
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Gaziosmanpasa Research and Education Hospital<br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Recent advances in the chromatographic determination of the most commonly used anti-hepatitis C drug Sofosbuvir and its co-administered drugs in human plasma</strong> - Sofosbuvir is a direct-acting antiviral drug that inhibits hepatitis C virus (HCV) NS5B polymerase which in turn reflects on the virus replication inside biological systems. The vital importance of sofosbuvir is not only based on its effect on HCV but also on other lethal viruses such as Zika and SARS-COVID-19. Accordingly, there is a continuous shedding of light on the development and validation of accurate and fast analytical methods for the determination of sofosbuvir in different…</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>Disruption of the biological activity of protease-activated receptors2/4 in adults rather than children in SARS CoV-2 virus-mediated mortality in COVID-19 infection</strong> - One of the most remarkable results in 2019 is the reduced prevalence and death of children from coronavirus infection (COVID-19). In 2019, a worldwide pandemic impacted around 0.1 billion individuals, with over 3.5 million mortality reported in the literature. There is minimal knowledge on SARS-CoV-2 infection immunological responses in kids. Studies have been focused mostly on adults and children since the course of pediatric sickness is often short. In adults, severe COVID-19 is related to an…</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>Active matrix metalloproteinase-8 (aMMP-8) point-of-care test (POCT) in the COVID-19 pandemic</strong> - INTRODUCTION: Active matrix metalloproteinase (aMMP)-8 utilized in point-of-care testing (POCT) is regarded as a potential biomarker for periodontal and peri-implant diseases. Various host and microbial factors eventually influence the expression, degranulation, levels and activation of aMMP-8. The type of oral fluids (saliva, mouthrinse, gingival crevicular and peri-implant sulcular fluids [GCF/PISF], respectively) affect the analysis.</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 IRGM establishes a robust antiviral immune state to restrict pathogenic viruses</strong> - The type I interferon (IFN) response is the major host arsenal against invading viruses. IRGM is a negative regulator of IFN responses under basal conditions. However, the role of human IRGM during viral infection has remained unclear. In this study, we show that IRGM expression is increased upon viral infection. IFN responses induced by viral PAMPs are negatively regulated by IRGM. Conversely, IRGM depletion results in a robust induction of key viral restriction factors including IFITMs,…</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>Thiol-Mediated Uptake</strong> - This Perspective focuses on thiol-mediated uptake, that is, the entry of substrates into cells enabled by oligochalcogenides or mimics, often disulfides, and inhibited by thiol-reactive agents. A short chronology from the initial observations in 1990 until today is followed by a summary of cell-penetrating poly(disulfide)s (CPDs) and cyclic oligochalcogenides (COCs) as privileged scaffolds in thiol-mediated uptake and inhibitors of thiol-mediated uptake as potential antivirals. In the spirit 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>Youth Relationships in the Era of COVID-19: A Mixed-Methods Study Among Adolescent Girls and Young Women in Kenya</strong> - CONCLUSIONS: COVID-19 disrupted adolescent girls’ and young women’s romantic relationships, depriving some of partner emotional support and exposing others to sexual violence, early pregnancy, and economically motivated transactional relationships. Increased social support systems, including access to psychosocial services, are needed in low-income communities in Kilifi, Kisumu, and Nairobi, in particular the informal settlement areas, to mitigate COVID-19’s consequences on girls’ SRH.</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>Proteflazid effectiveness for prevention and treatment of acute viral respiratory infections in the conditions of COVID-19</strong> - CONCLUSIONS: The statistical analysis confirmed the effectiveness of the drug Proteflazid® for the prevention and treatment of COVID-19, as, when compared with official actual data, regarding the main indicators of the incidence of COVID-19: there were no fatalities; the average treatment period decreased (1.8 times); the proportion of recovered increased (at least 1.5 times); the proportion of sick medical workers in the total population of sick medical workers decreased (2.2 times); 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>The highly protective natural medical agents against COVID-19</strong> - CONCLUSION: This study is the first in terms of reducing the harmful effect of COVID-19 by providing effective results in a short time by guiding the experimental studies to reveal the inhibitory effect of COVID-19 (Tab. 3, Fig. 5, Ref. 25). Text in PDF www.elis.sk Keywords: COVID-19, Carvacrol, docking Cucurbitacin-E and I.</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>Structure-based design of antisense oligonucleotides that inhibit SARS-CoV-2 replication</strong> - Antisense oligonucleotides (ASOs) are an emerging class of drugs that target RNAs. Current ASO designs strictly follow the rule of Watson-Crick base pairing along target sequences. However, RNAs often fold into structures that interfere with ASO hybridization. Here we developed a structure-based ASO design method and applied it to target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our method makes sure that ASO binding is compatible with target structures in three-dimensional…</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>Evidence of neutralizing antibodies against SARS-CoV-2 in domestic cats living with owners with a history of COVID-19 in Lima - Peru</strong> - SARS-CoV-2 can infect a variety of wild and domestic animals worldwide. Of these, domestic cats are highly susceptible species and potential viral reservoirs. As such, it is important to investigate disease exposure in domestic cats in areas with active community transmission and high disease prevalence. In this report we demonstrate the presence of serum neutralizing antibodies against the receptor binding-domain (RBD) of the SARS-CoV-2 in cats whose owners had been infected with SARS-CoV-2 in…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 and the Role of Stem Cells</strong> - There is currently an ongoing coronavirus respiratory disease (COVID-19) pandemic that is caused by SARS-CoV-2 virus, which emerged out of Wuhan, China. In severe cases, the disease can progress to respiratory distress, hypoxia, and multi-organ failure, all of which are associated with high mortality. Mesenchymal stem cells (MSCs) possess potent and broad-ranging immunomodulatory activities. MSCs have demonstrated their impressive ability to inhibit lung damage, reduce inflammation, attenuate…</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>Immunological evaluation of an inactivated SARS-CoV-2 vaccine in rhesus macaques</strong> - Because of the relatively limited understanding of COVID-19 pathogenesis, immunological analysis for vaccine development is needed. Mice and macaques were immunized with an inactivated SARS-CoV-2 vaccine prepared by two inactivators. Various immunological indexes were tested, and viral challenges were performed on day 7 or 150 after booster immunization in monkeys. This inactivated SARS-CoV-2 vaccine was produced by sequential inactivation with formaldehyde followed by propiolactone. The various…</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>Epigallocatechin gallate from green tea effectively blocks infection of SARS-CoV-2 and new variants by inhibiting spike binding to ACE2 receptor</strong> - CONCLUSIONS: These data support further clinical evaluation and development of EGCG as a novel, safe, and cost-effective natural product for prevention/treatment of SARS-CoV-2 transmission and infection.</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>Updated pharmacological effects of Lonicerae japonicae flos, with a focus on its potential efficacy on coronavirus disease-2019 (COVID-19)</strong> - Lonicerae japonicae flos (LJF), known as Jin Yin Hua in Chinese, is one of the most commonly used traditional Chinese herbs and nutraceuticals. Nowadays, LJF is broadly applied in an array of afflictions, such as fever, sore throat, flu infection, cough, and arthritis, with the action mechanism to be elucidated. Here, we strove to summarize the main phytochemical components of LJF and review its updated pharmacological effects, including inhibition of inflammation, pyrexia, viruses, and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 spike promotes inflammation and apoptosis through autophagy by ROS-suppressed PI3K/AKT/mTOR signaling</strong> - BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection-induced inflammatory responses are largely responsible for the death of novel coronavirus disease 2019 (COVID-19) patients. However, the mechanism by which SARS-CoV-2 triggers inflammatory responses remains unclear. Here, we aimed to explore the regulatory role of SARS-CoV-2 spike protein in infected cells and attempted to elucidate the molecular mechanism of SARS-CoV-2-induced inflammation.</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<ul>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Anti-Sars-Cov-2 Neutralizing Antibodies</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333857732">link</a></p></li>
|
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Expression Vector for Anti-Sars-Cov-2 Neutralizing Antibodies</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333857737">link</a></p></li>
|
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>DEVELOPMENT OF CNN SCHEME FOR COVID-19 DISEASE DETECTION USING CHEST RADIOGRAPH</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333857177">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-COV-2 BINDING PROTEINS</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333402004">link</a></p></li>
|
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A PROCESS FOR PREPARING MONTELUKAST SODIUM FOR TREATING COVID 19 PATIENTS</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333857132">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IDENTIFICATION OF ANTI-COVID 19 AGENT SOMNIFERINE AS INHIBITOR OF MPRO & ACE2-RBD INTERACTION</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333857079">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Deep Learning Based System For Detection of Covid-19 Disease of Patient At Infection Risk.</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333857030">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>鼠抗新型冠状病毒N蛋白杂交瘤细胞株,单克隆抗体及应用</strong> - 本发明提供两株鼠抗新型冠状病毒N蛋白杂交瘤细胞株,单克隆抗体及应用,通过小鼠杂交瘤单克隆抗体筛选及RT‑PCR法克隆Ig可变区基因,获得稳定分泌抗新型冠状病毒N蛋白抗体的杂交瘤细胞株及其可变区序列,并用ELISA方式对抗体结合特异性进行了鉴定,为抗新型冠状病毒N蛋白基因工程抗体的研发奠定了基础;该鼠源性新型冠状病毒N蛋白单克隆抗体与新型冠状病毒N蛋白反应高效价,且结合特异性强,可用于新型冠状病毒N蛋白的检测,以该抗体为原料开发的检测试剂盒具备很好的临床应用价值。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN334790381">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>자외선살균등</strong> - 본 발명은 사람의 의복이나 사용한 마스크 등에 부착하여 있다 호흡기로 유입되어 감염을 유발할 수 있는 COVID-19와 같은 유해균류를 간편하게 살균하기 위한 휴대용 자와선살균등에 관한 것이다. 반감기가 길고 인체에 유해한 오존을 발생하지 않으면서 탁월한 살균능력이 있는 250~265nm(최적은 253.7nm) 파장의 자외선을 발광하는 자외선램프를 본 발명의 막대형의 자외선살균등 광원으로 사용하고 비광원부를 손으로 잡고 의복이나 사용한 마스크 등 유해균류가 부착되었을 것으로 의심되는 곳에 자외선을 조사하여 간편하게 유해균류를 살균하므로써 감염을 예방하기 위한 휴대용 자외선살균등에 관함 것이다. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=KR332958765">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>图像识别方法、装置、电子设备和计算机可读存储介质</strong> - 本发明实施例公开了一种图像识别方法、装置、电子设备和计算机可读存储介质;本发明实施例在获取人脸图像样本后,对人脸图像样本进行空间特征提取,并基于提取出的图像特征和人脸标签信息对预设人脸识别模型进行训练,得到训练后人脸识别模型,然后,对图像特征进行域特征提取,得到人脸图像样本的类别特征,然后,基于类别特征和类别标签信息确定人脸图像样本的特征分类结果,然后,根据特征分类结果与训练后人脸识别模型进行修正,并采用修正后人脸识别模型对待识别人脸图像进行识别;该方案可以提升图像识别的效率。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN334806131">link</a></p></li>
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