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<title>06 July, 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><strong>POLICY OF TIME ECONOMIC RECOVERY COVID-19 PANDEMIC IN INDONESIA YEAR 2020-2021</strong> -
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The COVID-19 pandemic for almost two years has had a very extraordinary and frightening impact, there have been 2.3 million cases of covid-19 with a cure rate of 84% and a death rate of 2.6% in July 2021. The Covid-19 pandemic has not only created a humanitarian disaster but has an impact National economic downturn, such as negative economic growth, declining purchasing power, increasing poverty and uncontrolled unemployment. The government’s policy by carrying out a two-legged policy, the first is to break the chain of the spread of this pandemic with regulations and health protocol policies. The second is economic recovery during the pandemic with social assistance to the community, SMEs and industrialization so that they still have purchasing power to move the real sector. Inaccurate data, limited infrastructure and budget constraints are the biggest obstacles to economic recovery during the pandemic. UKMM is the final foundation and backbone of the national economy in the midst of an economic recession in its second year.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/rvmcu/" target="_blank">POLICY OF TIME ECONOMIC RECOVERY COVID-19 PANDEMIC IN INDONESIA YEAR 2020-2021</a>
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</div></li>
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<li><strong>Collaboration: Exploring the Postgraduate Researcher’s superpower for addressing inequalities within academia</strong> -
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Inequalities within academia are rampant. Sexism, racism, classism and discrimination impose huge barriers to those entering academic work or study. These issues are amplified in times of crisis, such as COVID-19. As postgraduate researchers, we can often feel powerless to address these inequalities. We possess little status in academic power structures, and as such it can be difficult to ‘rock the boat’ or diverge from normalised patterns of discrimination within our fields. In this essay, I argue that while we may lack status, postgraduates can adapt and diversify our collaborations with others to effectively address inequality. I outline how collaboration can be a vital tool for elevating underrepresented voices within and outside academia and examine how students with funding in particular can play an important role in this. In diversifying our citations, networks and methods of collaboration, we can ensure increasing opportunities are available for underrepresented groups throughout the academic pipeline. As the next generation of scholars, postgraduate researchers can change the game for underrepresented groups, and ensuring we collaborate diversely is our superpower for doing so.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/d8et9/" target="_blank">Collaboration: Exploring the Postgraduate Researcher’s superpower for addressing inequalities within academia</a>
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</div></li>
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<li><strong>A Kozak-related non-coding deletion effectively increases B.1.1.7 transmissibility</strong> -
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<div>
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The high transmissibility acquisition of SARS-CoV-2 Variant of Concern (VOC) B.1.1.7 remains unclear and only mutations in coding regions have been examined. We analyzed 875,338 high-quality SARS-CoV-2 genomic sequences and the epidemiology metadata. The occurrence of a non-coding deletion (g.a28271-) in the B.1.1.7 background immediately causes the rapid spread of B.1.1.7. The number of B.1.1.7-like strains lacking the deletion is significantly less than that of B.1.1.7 strains (n= 259 vs 92,688, P-value<4.9e-324). The same highly significant statistics is observed in different countries, gender and age groups. However, the deletion alone does not cause such high viral transmissibility. The deletion and another mutation (g.gat28280cta) co-affect translational efficiency of the genes N and ORF9b by changing the core Kozak sites. The deletion interacts synergistically with S:p.P681H and S:p.T716I to increase viral transmissibility. Therefore, the Kozak-related non-coding deletion, also carried by the Delta VOC, is crucial for the high viral transmissibility of SARS-CoV-2.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.04.30.442029v2" target="_blank">A Kozak-related non-coding deletion effectively increases B.1.1.7 transmissibility</a>
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<li><strong>‘Distancers’ and ‘non-distancers’? The potential social-psychological impact of moralising COVID-19 mitigating practices on sustained behaviour change</strong> -
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COVID-19 mitigating practices such as “hand-washing”, “social distancing” or “social isolating” are constructed as ‘moral imperatives’, required to avert harm to oneself and others. Adherence to COVID-19 mitigating practices is presently high among the general public, and stringent lockdown measures supported by legal and policy intervention has facilitated this. In the coming months, however, as rules are being relaxed and individuals become less strict, and thus the ambiguity in policy increases, the maintenance of recommended social distancing norms will rely on more informal social-interactional processes. We argue that the moralisation of these practices, twinned with relaxations of policy, may likely cause interactional tension between those individuals who do vs. those who do not uphold social distancing in the coming months: i.e., derogation of those who adhere strictly to COVID-19 mitigating practices and group polarisation between ‘distancers’ and ‘non-distancers’. In this paper we explore how and why these processes might come to pass, their impact on an overall societal response to COVID-19, and the need to factor such processes into decisions regarding how to lift restrictions.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/dbkj6/" target="_blank">‘Distancers’ and ‘non-distancers’? The potential social-psychological impact of moralising COVID-19 mitigating practices on sustained behaviour change</a>
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</div></li>
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<li><strong>Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques</strong> -
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To prepare for future coronavirus (CoV) pandemics, it is desirable to generate vaccines capable of eliciting neutralizing antibody responses against multiple CoVs. Because of the phylogenetic similarity to humans, rhesus macaques are an animal model of choice for many virus-challenge and vaccine-evaluation studies, including SARS-CoV-2. Here, we show that immunization of macaques with SARS-CoV-2 spike (S) protein generates potent receptor binding domain cross-neutralizing antibody (nAb) responses to both SARS-CoV-2 and SARS-CoV-1, in contrast to human infection or vaccination where responses are typically SARS-CoV-2-specific. Furthermore, the macaque nAbs are equally effective against SARS-CoV-2 variants of concern. Structural studies show that different immunodominant sites are targeted by the two primate species. Human antibodies generally target epitopes strongly overlapping the ACE2 receptor binding site (RBS), whereas the macaque antibodies recognize a relatively conserved region proximal to the RBS that represents another potential pan-SARS-related virus site rarely targeted by human antibodies. B cell repertoire differences between the two primates appear to significantly influence the vaccine response and suggest care in the use of rhesus macaques in evaluation of vaccines to SARS-related viruses intended for human use.
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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/10.1101/2021.07.05.451222v1" target="_blank">Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques</a>
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<li><strong>Increased frequency of recurrent in-frame deletions in new expanding lineages of SARS CoV-2 reflects immune selective pressure</strong> -
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Most of the attention in the surveillance of evolution of SARS-CoV-2 has been centered on single nucleotide substitutions in the spike glycoprotein. We show that in-frame deletions (IFDs) also play a significant role in the evolution of viral genome. The percentage of genomes and lineages with IFDs is growing rapidly and they co-occur independently in multiple lineages, including emerging variants of concerns. IFDs distribution is correlated with spike mutations associated with immune escape and concentrated in proteins involved in interactions with the host immune system. Structural analysis suggests that IFDs remodel viral proteins surfaces at common epitopes and interaction interfaces, affecting the virus interactions with the immune system. We hypothesize that the increased frequency of IFDs is an adaptive response to elevated global population immunity.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.07.04.451027v1" target="_blank">Increased frequency of recurrent in-frame deletions in new expanding lineages of SARS CoV-2 reflects immune selective pressure</a>
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<li><strong>SARS-CoV-2 environmental contamination from hospitalised COVID-19 patients receiving aerosol generating procedures</strong> -
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ABSTRACT Background. Continuous positive airways pressure (CPAP) and high-flow nasal oxygen (HFNO) are considered “aerosol-generating procedures” (AGPs) in the treatment of COVID-19. We aimed to measure air and surface environmental contamination of SARS-CoV-2 virus when CPAP and HFNO were used, compared with supplemental oxygen, to investigate the potential risks of viral transmission to healthcare workers and patients. Methods. 30 hospitalised patients with COVID-19 requiring supplemental oxygen, with a fraction of inspired oxygen ≥0.4 to maintain oxygen saturations ≥94%, were prospectively enrolled into an observational environmental sampling study. Participants received either supplemental oxygen, CPAP or HFNO (n=10 in each group). A nasopharyngeal swab, three air and three surface samples were collected from each participant and the clinical environment. RT qPCR analyses were performed for viral and human RNA, and positive/suspected-positive samples were cultured for the presence of biologically viable virus. Results. Overall 21/30 (70%) of participants tested positive for SARS-CoV-2 RNA in the nasopharynx. In contrast, only 4/90 (4%) and 6/90 (7%) of all air and surface samples tested positive (positive for E and ORF1a) for viral RNA respectively, although there were an additional 10 suspected-positive samples in both air and surfaces samples (positive for E or ORF1a). CPAP/HFNO use or coughing was not associated with significantly more environmental contamination. Only one nasopharyngeal sample was culture positive. Conclusions. The use of CPAP and HFNO to treat moderate/severe COVID-19 was not associated with significantly higher levels of air or surface viral contamination in the immediate care environment.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.07.04.21259945v1" target="_blank">SARS-CoV-2 environmental contamination from hospitalised COVID-19 patients receiving aerosol generating procedures</a>
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<li><strong>Angiotensin II receptor I auto-antibodies following SARS-CoV-2 infection</strong> -
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BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with endothelial activation and coagulopathy, which may be related to pre-existing or infection-induced pro-thrombotic autoantibodies such as those targeting angiotensin II type I receptor (AT1R-Ab). METHODS: We compared prevalence and levels of AT1R-Ab in COVID-19 cases with mild or severe disease to age and sex matched negative controls. RESULTS: There were no significant differences between cases and controls. However, there were trends toward a higher proportion with AT1R-Ab positivity among severe cases versus controls (32% vs. 11%, p=0.1) and higher levels in those with mild COVID-19 compared to controls (median 9.5U/mL vs. 5.9U/mL, p=0.06). CONCLUSIONS: These findings suggest that AT1R-Ab are not consistently associated with COVID-19 but do not exclude a contribution to endothelial pathology in a subset of people.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.06.30.21259796v1" target="_blank">Angiotensin II receptor I auto-antibodies following SARS-CoV-2 infection</a>
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<li><strong>Hydrogel-based slow release of a receptor-binding domain subunit vaccine elicits neutralizing antibody responses against SARS-CoV-2</strong> -
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The development of effective vaccines that can be rapidly manufactured and distributed worldwide is necessary to mitigate the devastating health and economic impacts of pandemics like COVID-19. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, which mediates host cell entry of the virus, is an appealing antigen for subunit vaccines because it is efficient to manufacture, highly stable, and a target for neutralizing antibodies. Unfortunately, RBD is poorly immunogenic. While most subunit vaccines are commonly formulated with adjuvants to enhance their immunogenicity, we found that clinically-relevant adjuvants Alum, AddaVax, and CpG/Alum were unable to elicit neutralizing responses following a prime-boost immunization. Here we show that sustained delivery of an RBD/CpG/Alum subunit vaccine in an injectable polymer-nanoparticle (PNP) hydrogel depot increased total anti-RBD antibody titers and elicited potent anti-spike titers, providing broader protection against SARS-CoV-2 variants of concern compared to bolus administration of the same vaccine and vaccines comprising other clinically-relevant adjuvant systems. Notably, a SARS-CoV-2 spike-pseudotyped lentivirus neutralization assay revealed that hydrogel-based vaccines elicited potent neutralizing responses when bolus vaccines did not. Together, these results suggest that slow delivery of RBD subunit vaccines with PNP hydrogels can significantly enhance the immunogenicity of RBD and induce neutralizing humoral immunity.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.03.31.437792v2" target="_blank">Hydrogel-based slow release of a receptor-binding domain subunit vaccine elicits neutralizing antibody responses against SARS-CoV-2</a>
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<li><strong>An Immune Cell Atlas Reveals Dynamic COVID-19 Specific Neutrophil Programming Amenable to Dexamethasone Therapy</strong> -
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SARS-CoV-2 is a novel coronavirus that causes acute respiratory distress syndrome (ARDS), death and long-term sequelae. Innate immune cells are critical for host defense but are also the primary drivers of ARDS. The relationships between innate cellular responses in ARDS resulting from COVID-19 compared to other causes of ARDS, such as bacterial sepsis is unclear. Moreover, the beneficial effects of dexamethasone therapy during severe COVID-19 remain speculative, but understanding the mechanistic effects could improve evidence-based therapeutic interventions. To interrogate these relationships, we developed an scRNA-Seq and plasma proteomics atlas (biernaskielab.ca/COVID_neutrophil). We discovered that compared to bacterial ARDS, COVID-19 was associated with distinct neutrophil polarization characterized by either interferon (IFN) or prostaglandin (PG) active states. Neutrophils from bacterial ARDS had higher expression of antibacterial molecules such as PLAC8 and CD83. Dexamethasone therapy in COVID patients rapidly altered the IFNactive state, downregulated interferon responsive genes, and activated IL1R2+ve neutrophils. Dexamethasone also induced the emergence of immature neutrophils expressing immunosuppressive molecules ARG1 and ANXA1, which were not present in healthy controls. Moreover, dexamethasone remodeled global cellular interactions by changing neutrophils from information receivers into information providers. Importantly, male patients had higher proportions of IFNactive neutrophils, a greater degree of steroid-induced immature neutrophil expansion, and increased mortality benefit compared to females in the dexamethasone era. Indeed, the highest proportion of IFNactive neutrophils was associated with mortality. These results define neutrophil states unique to COVID-19 when contextualized to other life-threatening infections, thereby enhancing the relevance of our findings at the bedside. Furthermore, the molecular benefits of dexamethasone therapy are also defined, and the identified pathways and plasma proteins can now be targeted to develop improved therapeutics.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.04.18.440366v2" target="_blank">An Immune Cell Atlas Reveals Dynamic COVID-19 Specific Neutrophil Programming Amenable to Dexamethasone Therapy</a>
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<li><strong>To knot or not to knot: Multiple conformations of the SARS-CoV-2 frameshifting RNA element</strong> -
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The SARS-CoV-2 frameshifting RNA element (FSE) is an excellent target for therapeutic intervention against Covid-19. This small gene element employs a shifting mechanism to pause and backtrack the ribosome during translation between Open Reading Frames 1a and 1b, which code for viral polyproteins. Any interference with this process has profound effect on viral replication and propagation. Pinpointing the structures adapted by the FSE and associated structural transformations involved in frameshifting has been a challenge. Using our graph-theory-based modeling tools for representing RNA secondary structures, “RAG” (RNA-As-Graphs), and chemical structure probing experiments, we show that the 3-stem H-type pseudoknot (3_6 dual graph), long assumed to be the dominant structure has a viable alternative, an HL-type 3-stem pseudoknot (3_3) for longer constructs. In addition, an unknotted 3-way junction RNA (3_5) emerges as a minor conformation. These three conformations share Stems 1 and 3, while the different Stem 2 may be involved in a conformational switch and possibly associations with the ribosome during translation. For full-length genomes, a stem-loop motif (2_2) may compete with these forms. These structural and mechanistic insights advance our understanding of the SARS-CoV-2 frameshifting process and concomitant virus life cycle, and point to three avenues of therapeutic intervention.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.03.31.437955v2" target="_blank">To knot or not to knot: Multiple conformations of the SARS-CoV-2 frameshifting RNA element</a>
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<li><strong>Low dose mRNA-1273 COVID-19 vaccine generates durable T cell memory and antibodies enhanced by pre-existing crossreactive T cell memory</strong> -
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Understanding human immune responses to SARS-CoV-2 RNA vaccines is of interest for a panoply of reasons. Here we examined vaccine-specific CD4+ T cell, CD8+ T cell, binding antibody, and neutralizing antibody responses to the 25 ug Moderna mRNA-1273 vaccine over 7 months post-immunization, including multiple age groups, with a particular interest in assessing whether pre-existing crossreactive T cell memory impacts vaccine-generated immunity. Low dose (25 ug) mRNA-1273 elicited durable Spike binding antibodies comparable to that of convalescent COVID-19 cases. Vaccine-generated Spike memory CD4+ T cells 6 months post-boost were comparable in quantity and quality to COVID-19 cases, including the presence of TFH cells and IFNg-expressing cells. Spike CD8+ T cells were generated in 88% of subjects, with equivalent percentages of CD8+ T cell memory responders at 6 months post-boost compared to COVID-19 cases. Lastly, subjects with pre-existing crossreactive CD4+ T cell memory had increased CD4+ T cell and antibody responses to the vaccine, demonstrating a biological relevance of SARS-CoV-2 crossreactive CD4+ T cells.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.06.30.21259787v1" target="_blank">Low dose mRNA-1273 COVID-19 vaccine generates durable T cell memory and antibodies enhanced by pre-existing crossreactive T cell memory</a>
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<li><strong>Will Vaccine-derived Protective Immunity Curtail COVID-19 Variants in the US?</strong> -
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Multiple effective vaccines are currently being deployed to combat the COVID-19 pandemic (caused by SARS-COV-2), and are viewed as the major factor in marked reductions in disease burden in regions around the world with moderate to high coverage of these vaccines. The effectiveness of COVID-19 vaccination programs is, however, significantly threatened by the emergence of new SARS-COV-2 variants that, in addition to being more transmissible and potentially more virulent than the wild (resident) strain, may at least partially evade existing vaccines. A new two-strain (one resident, the other wild) and two-group (vaccinated or otherwise) mechanistic mathematical model is designed and used to assess the impact of the vaccine-induced cross-protective efficacy on the spread the COVID-19 pandemic in the United States. Analysis of the model, which is fitted using COVID-19 mortality data for the US, shows that vaccine-induced herd immunity can be achieved if 61% of the American population is fully vaccinated with the Pfizer or Moderna vaccines. Parameter sensitivity analysis suggests three main factors that significantly affect the COVID-19 burden in the US, namely (a) daily vaccination rate, (b) the level of cross-protection the vaccines offer against the variant, and (c) the relative infectiousness of the dominant variant relative to the wild strain. This study further suggests that a new variant can cause a significant disease surge in the US if (i) the vaccine coverage against the wild strain is low (roughly < 50%), (ii) the variant is much more transmissible (e.g., twice more transmissible) than the wild-type strain, or (iii) the level of cross-protection offered by the vaccine is relatively low (e.g., less than 70%). A new variant will not cause such surge in the US if it is only moderately more transmissible (e.g., 1:56 more transmissible) than the wild strain, at least 66% of the population of the US is fully vaccinated, and the three vaccines being deployed in the US (Pfizer, Moderna, and Johnson & Johnson) offer a moderate level of cross-protection against the variant.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.06.30.21259782v1" target="_blank">Will Vaccine-derived Protective Immunity Curtail COVID-19 Variants in the US?</a>
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<li><strong>Impact of regional heterogeneity on the severity of COVID-19</strong> -
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Background: We aimed to assess the impact of regional heterogeneity on the severity of COVID-19 in Japan. Methods: We included 27,865 cases registered between January 2020 and February 2021 in the COVID-19 Registry of Japan to examine the relationship between the National Early Warning Score (NEWS) of COVID-19 patients on the day of admission and the prefecture where the patients live. A hierarchical Bayesian model was used to examine the random effect of each prefecture in addition to the patients9 backgrounds. In addition, we compared the results of two models; one model included the number of beds secured for COVID-19 patients in each prefecture as one of the fixed effects, and the other model did not. Results: The results indicated that the prefecture had a substantial impact on the severity of COVID-19 on admission. Even when considering the effect of the number of beds separately, the heterogeneity caused by the random effect of each prefecture affected the severity of the case on admission. Conclusions: Our analysis revealed a possible association between regional heterogeneity and increased/decreased risk of severe COVID-19 infection on admission. This heterogeneity was derived not only from the number of beds secured in each prefecture but also from other factors.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.06.30.21259758v1" target="_blank">Impact of regional heterogeneity on the severity of COVID-19</a>
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<li><strong>Disinfection of SARS-CoV-2 using UVC reveals wavelength sensitivity contributes towards rapid virucidal activity</strong> -
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SARS-CoV-2 is a pathogen that can be disinfected using UVC. For effective inactivation strategies, design and implementation of UVC disinfection, knowledge of wavelength sensitivity, and disinfection rate of the relevant pathogen are required. This study aimed to determine the inactivation profile of SARS-CoV-2 using UVC irradiation with different wavelengths, in addition to validating surrogate models for SARS-CoV-2. Specifically, the study determined dosage, inactivation levels, and wavelength sensitivity of SARS-CoV-2. Assessment of SARS-CoV-2 (Strain USA/WA1-2020) inactivation at peak wavelength of 259, 268, 270, 275 and 280 nm was performed using plaque assay method. The UVC dose of 3.1 mJ/cm2 using 259 and 268 nm arrays yielded LRV2.32 and LRV2.44 respectively. With a dose of 5mJ/cm2, arrays of peak wavelengths at 259 and 268 nm obtained similar inactivation (LRV2.97 and LRV 2.80 respectively). The remaining arrays of longer wavelength, 270, 275 and 280 nm, demonstrated lower performances (LRV2.0 or less) with 5mJ/cm2. Additional study with the 268 nm array revealed that a dose of 6.25 mJ/cm2 (with 5 seconds or irradiation) is enough to obtain LRV3. These results determine that 259 and 268 nm are the most efficient wavelengths compared to longer UVC wavelengths, allowing the calculation of disinfection systems efficacy, and providing a benchmark for surrogates.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.06.30.21259769v1" target="_blank">Disinfection of SARS-CoV-2 using UVC reveals wavelength sensitivity contributes towards rapid virucidal activity</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>Cognitive and Psychological Disorders After Severe COVID-19 Infection</strong> - <b>Condition</b>: COVID 19<br/><b>Interventions</b>: Diagnostic Test: Cognitive assessment; Diagnostic Test: Imaging; Diagnostic Test: Routine care; Other: Psychiatric evaluation<br/><b>Sponsors</b>: Central Hospital, Nancy, France; Centre Hospitalier Universitaire de Besancon; University Hospital, Strasbourg, France; Centre Hospitalier Régional Metz-Thionville; Centre hospitalier Epinal; Hopitaux Civils de Colmar<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 1 Study to Assess Safety, Tolerability, PD, PK, Immunogenicity of IV NTR-441 Solution in Healthy Volunteers and COVID-19 Patients</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: NTR-441; Drug: Placebo<br/><b>Sponsor</b>: Neutrolis<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>COVID-19 Vaccinations With a Sweepstakes</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Behavioral: Philly Vax Sweepstakes<br/><b>Sponsors</b>: University of Pennsylvania; Philadelphia Department of Public Health<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>Covid-19 Virtual Recovery Study</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Behavioral: Strength RMT; Behavioral: Strength RMT and nasal breathing; Behavioral: Endurance RMT; Behavioral: Endurance RMT and nasal breathing; Behavioral: Low dose RMT<br/><b>Sponsor</b>: Mayo Clinic<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>Safety and Immunogenicity of LNP-nCOV saRNA-02 Vaccine Against SARS-CoV-2, the Causative Agent of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: LNP-nCOV saRNA-02 Vaccine<br/><b>Sponsor</b>: MRC/UVRI and LSHTM Uganda Research Unit<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate MVC-COV1901 Vaccine Against COVID-19 in Adolescents</strong> - <b>Condition</b>: Covid19 Vaccine<br/><b>Interventions</b>: Biological: MVC-COV1901(S protein with adjuvant); Biological: MVC-COV1901(Saline)<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>Efficacy of Inhaled Therapies in the Treatment of Acute Symptoms Associated With COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: inhaled beclametasone; Drug: Inahaled beclomethasone / formoterol / glycopyrronium<br/><b>Sponsors</b>: UPECLIN HC FM Botucatu Unesp; Chiesi Farmaceutici S.p.A.<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>Dapsone Coronavirus SARS-CoV-2 Trial (DAP-CORONA) COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Dapsone 85 mg PO BID; Drug: Placebo 85 mg PO BID<br/><b>Sponsors</b>: McGill University Health Centre/Research Institute of the McGill University Health Centre; Pulmonem Inc.<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 Patients Management During Home Isolation</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Procedure: Oxygen therapy and physical therapy; Device: Oxygen therapy<br/><b>Sponsor</b>: Cairo University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ivermectin Versus Standard Treatment in Mild COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: Ivermectin Tablets<br/><b>Sponsor</b>: Assiut University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SCALE-UP Utah: Community-Academic Partnership to Address COVID-19 Testing Among Utah Community Health Centers</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Behavioral: Text-Messaging (TM); Behavioral: Patient Navigation (PN)<br/><b>Sponsors</b>: University of Utah; Association for Utah Community Health; Utah Department of Health; National Institutes of Health (NIH)<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>SCALE-UP Utah: Community-Academic Partnership to Address COVID-19 Vaccination Rates Among Utah Community Health Centers</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Behavioral: Text-Messaging (TM); Behavioral: Patient Navigation (PN)<br/><b>Sponsors</b>: University of Utah; Association for Utah Community Health; Utah Department of Health; National Institutes of Health (NIH)<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>Chinese Herbal Formula for COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: mQFPD; Drug: organic brown rice<br/><b>Sponsor</b>: University of California, San Diego<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>Remdesivir- Ivermectin Combination Therapy in Severe Covid-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: Ivermectin<br/><b>Sponsor</b>: Assiut University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IRAK 4 Inhibitor (PF-06650833) in Hospitalized Patients With COVID-19 Pneumonia and Exuberant Inflammation.</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: PF-06650833; Drug: Matching Placebo<br/><b>Sponsors</b>: Giovanni Franchin, M.D, Ph.D; Pfizer<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>Laser-facilitated epicutaneous immunization of mice with SARS-CoV-2 spike protein induces antibodies inhibiting spike/ACE2 binding</strong> - The skin represents an attractive target tissue for vaccination against respiratory viruses such as SARS-CoV-2. Laser-facilitated epicutaneous immunization (EPI) has been established as a novel technology to overcome the skin barrier, which combines efficient delivery via micropores with an inherent adjuvant effect due to the release of danger-associated molecular patterns. Here we delivered the S1 subunit of the Spike protein of SARS-CoV-2 to the skin of BALB/c mice via laser-generated…</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>Phytotherapic Drugs For Covid19 Treatment: A Scoping Review</strong> - CONCLUSION: Altogether, the review presents the action mechanism of plant extracts rich in bioactive compounds and depicted potential antiviral activity against SARS-CoV-2. These plant bioactive compounds can serve as lead molecules to develop phytomedicine, ensuring all safety regulations in the clinical trials to treat or prevent COVID19 viral infections.</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>Mechanistic Aspects of Medicinal Plants and Secondary Metabolites against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)</strong> - CONCLUSION: Medicinal plants and/or their bioactive compounds with inhibitory effects against SARS-CoV-2 support the human immune system and help in fighting against COVID-19 and rejuvenating the immune system.</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>Triangle of cytokine storm, central nervous system involvement, and viral infection in COVID-19: the role of sFasL and neuropilin-1</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is identified as the cause of coronavirus disease 2019 (COVID-19), and is often linked to extreme inflammatory responses by over activation of neutrophil extracellular traps (NETs), cytokine storm, and sepsis. These are robust causes for multi-organ damage. In particular, potential routes of SARS-CoV2 entry, such as angiotensin-converting enzyme 2 (ACE2), have been linked to central nervous system (CNS) involvement. CNS has been…</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>Protein S: function, regulation, and clinical perspectives</strong> - PURPOSE OF REVIEW: Protein S (PS) is an essential natural anticoagulant. PS deficiency is a major contributor to acquired hypercoagulability. Acquired hypercoagulability causes myocardial infarction, stroke, and deep vein thrombosis in millions of individuals. Yet, despite its importance in hemostasis, PS is the least understood anticoagulant. Even after 40 years since PS was first described, we are still uncovering information about how PS functions. The purpose of this review is to highlight…</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>Boswellic acids/Boswellia serrata extract as a potential COVID-19 therapeutic agent in the elderly</strong> - The most severe cases of COVID-19, and the highest rates of death, are among the elderly. There is an urgent need to search for an agent to treat the disease and control its progression. Boswellia serrata is traditionally used to treat chronic inflammatory diseases of the lung. This review aims to highlight currently published research that has shown evidence of potential therapeutic effects of boswellic acids (BA) and B. serrata extract against COVID-19 and associated conditions. We reviewed…</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>Corilagin and 1,3,6-Tri-O-galloy-beta-D-glucose: potential inhibitors of SARS-CoV-2 variants</strong> - The COVID-19 disease caused by the virus SARS-CoV-2, first detected in December 2019, is still emerging through virus mutations. Although almost under control in some countries due to effective vaccines that are mitigating the worldwide pandemic, the urgency to develop additional vaccines and therapeutic treatments is imperative. In this work, the natural polyphenols corilagin and 1,3,6-tri-O-galloy-β-d-glucose (TGG) are investigated to determine the structural basis of inhibitor interactions as…</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>Roles of existing drug and drug targets for COVID-19 management</strong> - In December 2019, a highly transmissible, pneumonia epidemic caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), erupted in China and other countries, resulting in devastation and health crisis worldwide currently. The search and using existing drugs support to curb the current highly contagious viral infection is spirally increasing since the pandemic began. This is based on these drugs had against other related RNA-viruses such as MERS-Cov, 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>A new high-content screening assay of the entire hepatitis B virus life cycle identifies novel antivirals</strong> - CONCLUSIONS: The newly developed high-content assay is suitable to screen large-scale drug libraries, enables monitoring of the entire HBV life cycle, and discriminates between inhibition of early and late viral life cycle events.</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>Graphene Nanoplatelet and Graphene Oxide Functionalization of Face Mask Materials Inhibits Infectivity of Trapped SARS-CoV-2</strong> - Recent advancements in bidimensional nanoparticles production such as Graphene (G) and Graphene oxide (GO) have the potential to meet the need for highly functional personal protective equipment (PPE) against SARS-CoV-2 infection. The ability of G and GO to interact with microorganisms provides an opportunity to develop engineered textiles for use in PPE and limit the spread of COVID-19. PPE in current use in high-risk settings for COVID transmission provide only a physical barrier that…</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>Axonal Regeneration by Glycosaminoglycan</strong> - Like other biomolecules including nucleic acid and protein, glycan plays pivotal roles in various cellular processes. For instance, it modulates protein folding and stability, organizes extracellular matrix and tissue elasticity, and regulates membrane trafficking. In addition, cell-surface glycans are often utilized as entry receptors for viruses, including SARS-CoV-2. Nevertheless, its roles as ligands to specific surface receptors have not been well understood with a few exceptions such as…</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>Sphingolipids as Modulators of SARS-CoV-2 Infection</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic with severe consequences for afflicted individuals and the society as a whole. The biology and infectivity of the virus has been intensively studied in order to gain a better understanding of the molecular basis of virus-host cell interactions during infection. It is known that SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) via its spike protein. Priming of the virus by specific…</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 with a DPP-4 inhibitor at time of hospital admission for COVID-19 is not associated with improved clinical outcomes: data from the COVID-PREDICT cohort study in The Netherlands</strong> - CONCLUSIONS: We conclude that outpatient use of a DPP-4 inhibitor does not affect the clinical outcomes of patients with type 2 diabetes who are hospitalized because of COVID-19 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>SARS-CoV-2: Origin, Evolution, and Targeting Inhibition</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused an outbreak in Wuhan city, China and quickly spread worldwide. Currently, there are no specific drugs or antibodies that claim to cure severe acute respiratory diseases. For SARS-CoV-2, the spike (S) protein recognizes and binds to the angiotensin converting enzyme 2 (ACE2) receptor, allowing viral RNA to enter the host cell. The main protease (Mpro) is involved in the proteolytic process for mature non-structural proteins, 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>Depinar, a drug that potentially inhibits the binding and entry of COVID-19 into host cells based on computer-aided studies</strong> - CONCLUSION AND IMPLICATION: The results of this study were approved by in silico studies and due to the lack of time; we did not test the efficiency of these compounds through in vitro and in vivo studies. However, the selected compounds are all FDA approved and some are supplements like vitamin B12 and don’t cause any side effects for patients.</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>Differential detection kit for common SARS-CoV-2 variants in COVID-19 patients</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU328840861">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 anti-viral therapeutic</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU327160071">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>新型冠状病毒B.1.351南非突变株RBD的基因及其应用</strong> - 本发明属于生物技术领域,具体涉及新型冠状病毒B.1.351南非突变株RBD的基因及其应用。本发明的新型冠状病毒B.1.351南非突变株RBD的基因,其核苷酸序列如SEQIDNO.1或SEQIDNO.6所示。本发明通过优化野生型新型冠状病毒南非B.1.351南非突变株RBD的基因序列,并结合筛选确定了相对最佳序列,优化后序列产生的克隆表达效率比野生型新型冠状病毒B.1.351南非突变株RBD序列表达效率大幅提高,从而,本发明的新型冠状病毒B.1.351南非突变株RBD的基因可以用于制备新型冠状病毒疫苗。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN328990628">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A POLYHERBAL ALCOHOL FREE FORMULATION FOR ORAL CAVITY</strong> - The present invention generally relates to a herbal composition. Specifically, the present invention relates to a polyherbal alcohol free composition comprising of Glycyrrhiza glabra root extract, Ocimum sanctum leaf extract, Elettaria cardamomum fruit extract, Mentha spicata (Spearmint) oil and Tween 80 and method of preparation thereof. The polyherbal alcohol free composition of the present invention possesses excellent antimicrobial properties and useful for oral cavity. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN325690740">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种检测SARS-CoV-2的引物组合物及其应用</strong> - 本发明涉及一种检测SARS‑CoV‑2的引物组合物及其应用。所述引物组合物包括SEQ ID NO:1~SEQ ID NO:12所示的核酸序列。本发明利用所述引物组合物进行逆转录巢式PCR,并结合Sanger测序,能够快速、准确地获取SARS‑CoV‑2基因信息,从而能够实现快速检测SARS‑CoV‑2以及判断SARS‑CoV‑2突变株,且具备良好的准确性、灵敏度、特异性以及重复性。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN328990422">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>检测新型冠状病毒中和抗体的试剂盒及其应用</strong> - 本发明涉及生物技术领域,具体而言,提供了一种检测新型冠状病毒中和抗体的试剂盒及其应用。本发明提供的检测新型冠状病毒中和抗体试剂盒,具体包括(a)或(b)两种方案:(a)示踪物标记的RBD三聚体抗原,包被在固体支持物上的ACE2,以及,含有0.2‑10mg/mL十二烷基二甲基甜菜碱的工作液;(b)示踪物标记的ACE2,包被在固体支持物上的RBD三聚体抗原,以及,含有0.2‑10mg/mL十二烷基二甲基甜菜碱的工作液;其中,RBD三聚体抗原利用二硫键将刺突蛋白的RBD与S2亚基完全交联得到。十二烷基二甲基甜菜碱会显著提高RBD三聚体抗原与新冠中和性抗体结合速度,提升阳性样本平均发光强度,缩短检测时间。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN328990376">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种新冠病毒肺炎重症化预测系统及方法</strong> - 本发明涉及疾病预测技术领域,公开了一种新冠病毒肺炎重症化预测系统及方法,包括以下步骤:步骤一,采集患者血常规信息和用户信息;步骤二,将患者血常规信息按照用户信息进行等级分类;步骤三,将已经等级分类的患者血常规信息与对应等级的标准信息进行比较;步骤四,当患者血常规信息在标准信息范围内则判定患者为轻症患者,当患者血常规信息在标准信息范围外则判定患者为重症患者。本发明能够准确快速地区分轻症和重症。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN328308318">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MEDIDOR DE SATURACION</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=ES325874099">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>폐마스크 밀봉 회수기</strong> - 본 발명은 마스크 착용 후 버려지는 일회용 폐마스크를 비닐봉지에 넣은 후 밀봉하여 배출함으로써, 2차 감염을 예방하고 일반 생활폐기물과 선별 분리 배출하여 환경오염을 방지하는 데 그 목적이 있다. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=KR325788342">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>백신 냉각 및 해동 기능을 갖는 백신 보관장치</strong> - 본 발명은 백신 냉각 및 해동 기능을 갖는 백신 보관장치에 관한 것으로, 상, 하부하우징의 제1상, 하부누출방지공간에 냉각물질이 충입된 냉각파이프를 설치하되, 제2상, 하부누출방지공간에 가열물질이 충입된 가열파이프를 설치하여, 구획판부에 의해 구획된 백신냉각공간 및 백신해동공간 각각을 냉각 및 가열하고, 보조도어를 통해 백신냉각공간 내에 수용된 백신을 구획판부의 백신출구도어를 통해 백신해동공간으로 이동시켜, 백신해동공간 내에서 백신을 해동함으로써, 즉시 사용이 가능한 백신을 인출도어를 통해 인출할 수 있다. 본 발명에 따르면, 냉각파이프에 저장된 냉매에 의해 백신냉각공간 내의 온도가 극저온 상태로 변화되고, 극저온 상태를 유지하는 백신냉각공간 내에 백신을 저장하여, 안전하게 보관 할 수 있으며, 백신냉각공간 내의 백신을 백신해동공간 내로 이동시켜, 백신해동공간 내에서 백신을 해동할 수 있고, 이 해동된 백신을 인출도어를 통해 인출한 후 즉시 사용할 수 있어 백신을 해동하는 시간이 단축되며, 보조도어를 통해 백신냉각공간 내의 백신을 백신해동공간으로 이동시켜, 백신이 외기에 노출될 우려가 없으며, 백신냉각공간 내의 백신을 백신해동공간으로 이동시키거나 또는 인출도어를 통해 백신 인출시 정렬장치가 백신을 보조도어 및 인출도어 직하방에 자동 위치시킨다. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=KR327274025">link</a></p></li>
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