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211 lines
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<title>16 April, 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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>A very simple model to account for the rapid rise of the British variant of SARS-CoV-2 in several countries and the world</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Since its first detection in the UK in September 2020, a highly contagious version of the coronavirus, called the British variant or B.1.1.7 SARS-CoV-2 virus lineage, is rapidly spreading across several countries and becoming the dominant strain in the outbreak. Here it is shown that a very simple evolutionary model, when including the latest available data from March 2021, can fit the observed change in frequency of B.1.1.7 for several countries, regions of countries and the whole world with a single parameter which is almost universal.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.13.21254841v1" target="_blank">A very simple model to account for the rapid rise of the British variant of SARS-CoV-2 in several countries and the world</a>
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</div></li>
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<li><strong>The impact of COVID-19 upon the delivery of exercise services within cystic fibrosis clinics in the United Kingdom</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The COVID-19 pandemic has resulted in unprecedent change to clinical practice. As the impact upon delivery of exercise services for people with cystic fibrosis (CF) in the UK was unknown, this was characterised via a national survey. In total, 31 CF centres participated. Principal findings included a significant reduction in exercise testing, and widespread adaptation to deliver exercise training using telehealth methods. Promisingly, 71% stated that they would continue to use virtual methods of engaging patients in future practice. This does, however, highlight a need to develop sustainable and more standardised telehealth services further to manage patients moving forwards.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.12.21255205v1" target="_blank">The impact of COVID-19 upon the delivery of exercise services within cystic fibrosis clinics in the United Kingdom</a>
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</div></li>
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<li><strong>Preparations of Dutch emergency departments for the COVID-19 pandemic: a questionnaire-based study</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: The onset of the COVID-19 pandemic was characterized by rapidly increasing patient volumes, which necessitated a swift emergency department (ED) overhaul. Challenges mainly concerned surge capacity, frontline staff protection and the segregation of patients with suspected COVID-19. To date, only few studies have assessed nation-wide ED preparedness for the COVID-19 pandemic. This study aimed to form an overview of preparations that were taken in Dutch EDs during the initial phase of this public health crisis. Methods: This study was designed as a nation-wide, cross-sectional, questionnaire-based study among Dutch hospital organizations with an ED. The questionnaire was conducted between the first and the second wave of the COVID-19 pandemic in the Netherlands and contained close-ended and open-ended questions on changes in ED infrastructure, ED workforce adaptions and the role of emergency physicians (EPs) in the hospital crisis organizations. Results: Overall response rate was 79.5%. All EDs had made preparations in anticipation of a possible COVID-19 surge. Treatment capacity was expanded in 69.7% of EDs, with a median increase of 49% (IQR 32.5-72.7%). COVID-19 suspected patients were segregated from non-COVID-19 patients in 86.4% of EDs. Non-COVID-19 patients were more often assessed at alternative locations than patients with suspected COVID-19 infection. In 81.8% of EDs the workforce was expanded, which mainly concerned expansion of nursing staff. A formal role of EPs in the hospital crisis organizations was reported by 93.9% of EP staffed hospital organizations. Conclusion: All Dutch EDs made preparations for COVID-19 in a short time span and with many uncertainties. Preparations predominantly concerned expansion of treatment capacity and segregation of COVID-19 ED care. EPs had a prominent role, both in direct patient COVID-19 ED care and in the hospital crisis organizations. Although it is vital for EDs to be able to dynamically adapt to community needs, variability of pandemic ED preparedness was high.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.10.21254878v1" target="_blank">Preparations of Dutch emergency departments for the COVID-19 pandemic: a questionnaire-based study</a>
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</div></li>
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<li><strong>Evaluating the impact of keeping indoor dining closed on COVID-19 rates among large US cities: a quasi-experimental design</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Objective: Indoor dining is one of the potential key drivers of COVID-19 transmission. We leverage the heterogeneity in state government preemption of city indoor dining closures, to estimate the impact of keeping indoor dining closed on COVID-19 incidence. Methods: We obtained case rates and city/state re-opening dates from March to October 2020 in 11 U.S. cities. We categorized cities as (treatment) cities that were allowed by the state to reopen but kept indoor dining closed; and (comparison) cities that would have kept indoor dining closed but were preempted by their state and had to reopen indoor dining. Results: Keeping indoor dining closed was associated with a 43% (IRR=0.57, 95% CI 0.46 to 0.69) decline in COVID-19 incidence over 4-weeks compared with cities that reopened indoor dining. These results were consistent after testing alternative modeling strategies. Conclusions: Keeping indoor dining closed contributes to reductions in COVID-19 spread. Policy Implications: Evidence of the relationship between indoor dining and COVID-19 incidence can inform state and local decisions to restrict indoor dining as a tailored strategy to reduce COVID-19 incidence.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.12.21251656v1" target="_blank">Evaluating the impact of keeping indoor dining closed on COVID-19 rates among large US cities: a quasi-experimental design</a>
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</div></li>
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<li><strong>Strong anti-viral responses in pediatric COVID-19 patients in South Brazil</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Epidemiological evidence that COVID-19 manifests as a milder disease in children compared to adults has been reported by numerous studies, but the mechanisms underlying this phenomenon have not been characterized. It is still unclear how frequently children get infected, and/or generate immune responses to SARS-CoV-2. We have performed immune profiling of pediatric and adult COVID-19 patients in Brazil, producing over 38 thousand data points, asking if cellular or humoral immune responses could help explain milder disease in children. In this study, pediatric COVID-19 patients presented high viral titers. Though their non-specific immune profile was dominated by naive, non-activated lymphocytes, their dendritic cells expressed high levels of HLA-DR and were low in CX3CR1, indicating competence to generate immune responses that are not targeted to inflamed tissue. Finally, children formed strong specific antibody and T cell responses for viral structural proteins. Children s T cell responses differed from adults in that their CD8+ TNFα+ T cell responses were low for S peptide but significantly higher against N and M peptide pools. Altogether, our data support a scenario in which SARS-CoV-2 infected children may contribute to transmission, though generating strong and differential responses to the virus that might associate with protection in pediatric COVID-19 presentation.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.13.21255139v1" target="_blank">Strong anti-viral responses in pediatric COVID-19 patients in South Brazil</a>
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</div></li>
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<li><strong>Computationally prioritized drugs inhibit SARS-CoV-2 infection and syncytia formation</strong> -
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<div>
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New affordable therapeutic protocols for COVID-19 are urgently needed despite the increasing number of effective vaccines and monoclonal antibodies. To this end, there is increasing attention towards computational methods for drug repositioning and de novo drug design. Here, we systematically integrated multiple data-driven computational approaches to perform virtual screening and prioritize candidate drugs for the treatment of COVID-19. From the set of prioritized drugs, we selected a subset of representative candidates to test in human cells. Two compounds, 7-hydroxystaurosporine and bafetinib, showed synergistic antiviral effects in our in vitro experiments, and strongly inhibited viral-induced syncytia formation. Moreover, since existing drug repositioning methods provide limited usable information for de novo drug design, we extracted and prioritized the chemical substructures of the identified drugs, providing a chemical vocabulary that may help to design new effective drugs.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.04.15.440004v1" target="_blank">Computationally prioritized drugs inhibit SARS-CoV-2 infection and syncytia formation</a>
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</div></li>
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<li><strong>Time-series trend of pandemic SARS-CoV-2 variants visualized using batch-learning self-organizing map for oligonucleotide compositions</strong> -
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<div>
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To confront the global threat of coronavirus disease 2019, a massive number of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome sequences have been decoded, with the results promptly released through the GISAID database. Based on variant types, eight clades have already been defined in GISAID, but the diversity can be far greater. Owing to the explosive increase in available sequences, it is important to develop new technologies that can easily grasp the whole picture of the big-sequence data and support efficient knowledge discovery. An ability to efficiently clarify the detailed time-series changes in genome-wide mutation patterns will enable us to promptly identify and characterize dangerous variants that rapidly increase their population frequency. Here, we collectively analyzed over 150,000 SARS-CoV-2 genomes to understand their overall features and time-dependent changes using a batch-learning self-organizing map (BLSOM) for oligonucleotide composition, which is an unsupervised machine learning method. BLSOM can separate clades defined by GISAID with high precision, and each clade is subdivided into clusters, which shows a differential increase/decrease pattern based on geographic region and time. This allowed us to identify prevalent strains in each region and to show the commonality and diversity of the prevalent strains. Comprehensive characterization of the oligonucleotide composition of SARS-CoV-2 and elucidation of time-series trends of the population frequency of variants can clarify the viral adaptation processes after invasion into the human population and the time-dependent trend of prevalent epidemic strains across various regions, such as continents.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.04.15.439956v1" target="_blank">Time-series trend of pandemic SARS-CoV-2 variants visualized using batch-learning self-organizing map for oligonucleotide compositions</a>
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</div></li>
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<li><strong>Scalable, methanol-free manufacturing of the SARS-CoV-2 receptor binding domain in engineered Komagataella phaffii</strong> -
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<div>
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Prevention of COVID-19 on a global scale will require the continued development of high-volume, low-cost platforms for the manufacturing of vaccines to supply on-going demand. Vaccine candidates based on recombinant protein subunits remain important because they can be manufactured at low costs in existing large-scale production facilities that use microbial hosts like Komagataella phaffii (Pichia pastoris). Here, we report an improved and scalable manufacturing approach for the SARS-CoV-2 spike protein receptor binding domain (RBD); this protein is a key antigen for several reported vaccine candidates. We genetically engineered a manufacturing strain of K. phaffii to obviate the requirement for methanol-induction of the recombinant gene. Methanol-free production improved the secreted titer of the RBD protein by >5x by alleviating protein folding stress. Removal of methanol from the production process enabled scale up to a 1,200 L pre-existing production facility. This engineered strain is now used to produce an RBD-based vaccine antigen that is currently in clinical trials and could be used to produce other variants of RBD as needed for future vaccines.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.04.15.440035v1" target="_blank">Scalable, methanol-free manufacturing of the SARS-CoV-2 receptor binding domain in engineered Komagataella phaffii</a>
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</div></li>
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<li><strong>Evaluation of the SARS-CoV-2 inactivation efficacy associated with buffers from three kits used on high-throughput RNA extraction platforms</strong> -
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<div>
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Rapid and demonstrable inactivation of SARS-CoV-2 is crucial to ensure operator safety during high-throughput testing of clinical samples. The inactivation efficacy of SARS-CoV-2 was evaluated using commercially available lysis buffers from three viral RNA extraction kits used on two high-throughput (96-well) RNA extraction platforms (Qiagen QiaCube HT and the ThermoFisher Kingfisher Flex) in combination with thermal treatment. Buffer volumes and sample ratios were chosen for their optimised suitability for RNA extraction rather than inactivation efficacy and tested against a representative sample type; SARS-CoV-2 spiked into viral transport medium (VTM). A lysis buffer from the MagMax Pathogen RNA/DNA kit (ThermoFisher), used on the Kingfisher Flex, which included guanidinium isothiocycnate (GITC), a detergent, and isopropanol demonstrated a minimum inactivation efficacy of 1 x 105 TCID50/ml. An alternative lysis buffer from the MagMax Viral/Pathogen Nucleic Acid kit (Thermofisher) also used on the Kingfisher Flex and the lysis buffer from QIAamp 96 Virus QIAcube HT Kit (Qiagen) used on the QiaCube HT (both of which contained GITC and a detergent) reduced titres by 1 x 104 TCID50/ml but did not completely inactivate the virus. Heat treatment alone (15 minutes, 68 {degrees}C) did not completely inactivate the virus, demonstrating a reduction of 1 x 103 TCID50/ml. When inactivation methods included both heat treatment and addition of lysis buffer, all methods were shown to completely inactivate SARS-CoV-2 inactivation against the viral titres tested. Results are discussed in the context of the operation of a high-throughput diagnostic laboratory.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.04.14.439928v1" target="_blank">Evaluation of the SARS-CoV-2 inactivation efficacy associated with buffers from three kits used on high-throughput RNA extraction platforms</a>
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</div></li>
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<li><strong>SARS-CoV-2-associated ssRNAs activate inflammation and immunity via TLR7/8</strong> -
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<div>
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The inflammatory and IFN pathways of innate immunity play a key role in both resistance and pathogenesis of Coronavirus Disease 2019 (COVID-19). Innate sensors and SARS-CoV-2-Associated Molecular Patterns (SAMPs) remain to be completely defined. Here we identify single-stranded RNA (ssRNA) fragments from SARS-CoV-2 genome as direct activators of endosomal TLR7/8 and MyD88 pathway. The same sequences induced human DC activation in terms of phenotype and functions, such as IFN and cytokine production and Th1 polarization. A bioinformatic scan of the viral genome identified several hundreds of fragments potentially activating TLR7/8, suggesting that products of virus endosomal processing potently activate the IFN and inflammatory responses downstream these receptors. In vivo, SAMPs induced MyD88-dependent lung inflammation characterized by accumulation of proinflammatory and cytotoxic mediators and immune cell infiltration, as well as splenic DC phenotypical maturation. These results identify TLR7/8 as crucial cellular sensors of ssRNAs encoded by SARS-CoV-2 involved in host resistance and disease pathogenesis of COVID-19.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.04.15.439839v1" target="_blank">SARS-CoV-2-associated ssRNAs activate inflammation and immunity via TLR7/8</a>
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</div></li>
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<li><strong>Screen time in the COVID era: International trends of increasing use among 3- to 7-year-old children</strong> -
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<div>
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Objective: To evaluate changes in electronic screen-based media use in 3- to 7-year-old children across six countries as a result of the COVID-19 pandemic. Methods: Between April and July 2020, parents and/or guardians of 2516 children completed online survey measures reporting current (“now”) and retrospective (“before the pandemic”) screen-based media use for the purposes of entertainment, educational app use, and socializing with family and friends. Parents also reported family socioeconomic characteristics and impacts of the pandemic to their physical wellbeing (e.g., whether a family member or friend had been diagnosed with COVID-19) and social disruption (e.g., whether family experienced a loss of income or employment due to the pandemic). Results: On average, children engaged with screens over 50 minutes more during the pandemic than before. This was largely driven by increases in screen use for entertainment purposes (nearly 40 minutes) and for use of educational apps (over 20 minutes). There was no overall change in screen use for socializing with family and friends. Children from lower socioeconomic status households increased screen use both for entertainment and educational app use more so than did children from higher socioeconomic status households. Conclusions: The global pandemic caused by COVID-19 has affected young children’s lives in almost every way, including increasing overall electronic screen-based media use. As children’s lives become increasingly digital by necessity, further research is needed to better understand positive and negative consequences of electronic screen-based media use.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/nx9ew/" target="_blank">Screen time in the COVID era: International trends of increasing use among 3- to 7-year-old children</a>
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<li><strong>Big Five Predictors of Pandemic-Related Behavior and Emotions in the First and Second COVID-19 Pandemic Wave in Slovakia</strong> -
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<div>
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This study explores the effect of Big Five personality traits on behavioral and emotional responses to the COVID-19 pandemic. Personality traits of 248 Slovak persons were assessed twice before the pandemic using the Big Five Inventory 2. Behavioral and emotional responses to the pandemic were collected during the first and second pandemic wave (April and September 2020). The results showed a statistically significant decrease in all response domains and in COVID-19 fear between the first and the second pandemic wave, suggesting that psychological adaptation to the pandemic occurred during the interim period. The results identified several meaningful links between the traits and pandemic-related behavior and emotions, especially for neuroticism, extraversion, and conscientiousness. However, the effects of personality were higher for the first pandemic wave, suggesting that these effects vary across time probably because of changes in pandemic perception in the society.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/hp9t2/" target="_blank">Big Five Predictors of Pandemic-Related Behavior and Emotions in the First and Second COVID-19 Pandemic Wave in Slovakia</a>
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</div></li>
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<li><strong>A Novel and Expanding SARS-CoV-2 Variant, B.1.526, Identified in New York</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Recent months have seen surges of SARS-CoV-2 infection across the globe along with considerable viral evolution1-3. Extensive mutations in the spike protein may threaten efficacy of vaccines and therapeutic monoclonal antibodies4. Two signature mutations of concern are E484K, which plays a crucial role in the loss of neutralizing activity of antibodies, and N501Y, a driver of rapid worldwide transmission of the B.1.1.7 lineage. Here, we report the emergence of a novel variant lineage B.1.526 that contains E484K and its alarming rise to dominance in New York City in recent months. This variant is partially or completely resistant to two therapeutic monoclonal antibodies in clinical use. It is also less susceptible to neutralization by convalescent plasma or vaccinee sera by 4.1-fold or 3.3-3.6-fold, respectively. The B.1.526 lineage has now been reported from at least 32 states in the US and numerous other countries. B.1526 has been outpacing B.1.1.7 in Northern Manhattan, and both variants have been spreading throughout New York with comparable estimated doubling times. Such transmission dynamics, together with its resistance to therapeutic antibodies, would warrant B.1.526 as a SARS-CoV-2 variant of concern.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.02.23.21252259v2" target="_blank">A Novel and Expanding SARS-CoV-2 Variant, B.1.526, Identified in New York</a>
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<li><strong>Optimizing vaccine allocation for COVID-19 vaccines: potential role of single-dose vaccination.</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Most COVID-19 vaccines require two doses, however with limited vaccine supply, policymakers are considering single-dose vaccination as an alternative strategy. Using a mathematical model combined with optimization algorithms, we determined optimal allocation strategies with one and two doses of vaccine under various degrees of viral transmission. Under low transmission, we show that the optimal allocation of vaccine vitally depends on the single-dose efficacy (SDE). With high SDE, single-dose vaccination is optimal, pre- venting up to 22% more deaths than a strategy prioritizing two-dose vaccination for older adults. With low or moderate SDE, mixed vaccination campaigns with complete coverage of older adults are optimal. However, with modest or high transmission, vaccinating older adults first with two doses is best, preventing up to 41% more deaths than a single- dose vaccination given across all adult populations. Our work suggests that it is imperative to determine the efficacy and durability of single-dose vaccines, as mixed or single-dose vaccination campaigns may have the potential to contain the pandemic much more quickly.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.31.20249099v4" target="_blank">Optimizing vaccine allocation for COVID-19 vaccines: potential role of single-dose vaccination.</a>
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</div></li>
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<li><strong>Evaluation of efficiency and sensitivity of 1D and 2D sample pooling strategies for SARS-CoV-2 RT-qPCR screening purposes</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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To increase the throughput, lower the cost, and save scarce test reagents, laboratories can pool patient samples before SARS-CoV-2 RT-qPCR testing. While different sample pooling methods have been proposed and effectively implemented in some laboratories, no systematic and large-scale evaluations exist using real-life quantitative data gathered throughout the different epidemiological stages. Here, we use anonymous data from 9673 positive cases to simulate and compare 1D and 2D pooling strategies. We show that the optimal choice of pooling method and pool size is an intricate decision with a testing population-dependent efficiency-sensitivity trade-off and present an online tool to provide the reader with custom real-time pooling strategy recommendations.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.07.17.20152702v3" target="_blank">Evaluation of efficiency and sensitivity of 1D and 2D sample pooling strategies for SARS-CoV-2 RT-qPCR screening purposes</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Study in the Treatment of Patients With Moderate Course of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: COVID-globulin; Drug: Placebo<br/><b>Sponsor</b>: Microgen<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>The Effects of a Multi-factorial Rehabilitation Program for Healthcare Workers Suffering From Post-COVID-19 Fatigue Syndrome</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Exercise<br/><b>Sponsor</b>: Medical University of Vienna<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Nurse-Community Health Worker-Family Partnership Model: Addressing Uptake of COVID-19 Testing and Control Measures</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Nurse-Community-Family Partnership Intervention<br/><b>Sponsor</b>: New York 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>Study on Sequential Immunization of Recombinant COVID-19 Vaccine (Ad5 Vector) and RBD-based Protein Subunit Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: recombinant Ad5 vectored COVID-19 vaccine; Biological: RBD-based protein subunit vaccine (ZF2001) against COVID-19; Biological: trivalent split influenza vaccine<br/><b>Sponsor</b>: Jiangsu Province Centers for Disease Control and Prevention<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>Omega-3 Oil Use in COVID-19 Patients in Qatar</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Omega 3 fatty acid<br/><b>Sponsor</b>: Hamad Medical Corporation<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity of the Inactivated Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine Compared to Placebo</strong> - <b>Condition</b>: COVID-19 Vaccine<br/><b>Interventions</b>: Biological: Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine 4 µg/0.5 ml Vaccine; Biological: Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine 6 µg/0.5 ml Vaccine; Biological: Placebo<br/><b>Sponsor</b>: Kocak Farma<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>Study of Intravenous Ampion in Adult COVID-19 Patients Requiring Supplemental Oxygen</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Ampion; Other: Saline<br/><b>Sponsor</b>: Ampio Pharmaceuticals. Inc.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of Oral Immunotherapy With GcMAF in Hospitalized Patients With COVID-19 Pneumonia</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Dietary Supplement: Saisei Maf capsules<br/><b>Sponsor</b>: Dr. Spadera Lucrezia<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>ENO Breathe vs Usual Care in COVID-19 Recovery: An RCT</strong> - <b>Condition</b>: COVID-19 Recovery<br/><b>Intervention</b>: Other: ENO Breathe group<br/><b>Sponsors</b>: Imperial College London; Imperial College Healthcare NHS Trust<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>Rehabilitation for Patients With Persistent Symptoms Post COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Other: Concentrated rehabilitation for patients with persistent symptoms post COVID-19<br/><b>Sponsors</b>: Western Norway University of Applied Sciences; Helse-Bergen HF<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of FES Cycling After a Severe Form of COVID-19</strong> - <b>Condition</b>: Person With a Severe Form of COVID-19 That Caused an Acute Distress Respiratory Syndrome Treated by Mechanical Ventilation in Intensive Care Unit<br/><b>Interventions</b>: Behavioral: Physical therapy that include a standardized cycling training with functional electrical stimulation; Behavioral: Physical therapy that include a standardized cycling training with no additional functional electrical stimulation<br/><b>Sponsor</b>: Hospices Civils de Lyon<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of Favipiravir and Ribavirin Formulation for Treatment of COVID-19</strong> - <b>Conditions</b>: SARS-CoV2; COVID-19<br/><b>Interventions</b>: Drug: Ribavirin Capsules; Drug: Favipiravir<br/><b>Sponsors</b>: The Scientific and Technological Research Council of Turkey; Ankara City Hospital Bilkent; Istanbul Umraniye Training and Research Hospital; Koç University; Monitor CRO<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>Dasatinib for the Treatment of Moderate and Severe COVID-19</strong> - <b>Condition</b>: Symptomatic COVID-19 Infection Laboratory-Confirmed<br/><b>Interventions</b>: Drug: Dasatinib Anhydrous; Drug: Placebo Administration<br/><b>Sponsors</b>: University of Southern California; National Cancer Institute (NCI)<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of Three Different Doses of an Anti SARS-CoV-2 Hyperimmune Equine Serum in COVID-19 Patients</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: Anti SARS-CoV-2 equine hyperimmune serum; Biological: placebo<br/><b>Sponsors</b>: Caja Costarricense de Seguro Social; Universidad de Costa Rica; Ministry of Health Costa Rica<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>Viral Clearance, PK and Tolerability of Ensovibep in COVID-19 Patients</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: ensovibep<br/><b>Sponsor</b>: Molecular Partners AG<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Development of flexible electrochemical impedance spectroscopy-based biosensing platform for rapid screening of SARS-CoV-2 inhibitors</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells through the binding of its spike protein (S-protein) to the cell surface-expressing angiotensin-converting enzyme 2 (ACE2). Thus, inhibition of S-protein-ACE2 binding may impede SARS-CoV-2 cell entry and attenuate the progression of Coronavirus disease 2019 (COVID-19). In this study, an electrochemical impedance spectroscopy-based biosensing platform consisting of a recombinant ACE2-coated palladium nano-thin-film…</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 mutations acquired in mink reduce antibody-mediated neutralization</strong> - Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans to farmed mink has been observed in Europe and the US. In the infected animals, viral variants arose that harbored mutations in the spike (S) protein, the target of neutralizing antibodies, and these variants were transmitted back to humans. This raised concerns that mink might become a constant source of human infection with SARS-CoV-2 variants associated with an increased threat to human health 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>Synergistic Inhibition of SARS-CoV-2 Replication Using Disulfiram/Ebselen and Remdesivir</strong> - The SARS-CoV-2 replication and transcription complex (RTC) comprising nonstructural protein (nsp) 2-16 plays crucial roles in viral replication, reducing the efficacy of broad-spectrum nucleoside analog drugs such as remdesivir and evading innate immune responses. Most studies target a specific viral component of the RTC such as the main protease or the RNA-dependent RNA polymerase. In contrast, our strategy is to target multiple conserved domains of the RTC to prevent SARS-CoV-2 genome…</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>Intriguing Antiviral Modified Nucleosides: A Retrospective View into the Future Treatment of COVID-19</strong> - Great pioneers of nucleic acid chemistry had elucidated nucleic acid functions and structures and developed various antiviral modified nucleoside drugs. It is possible in theory that antiviral modified nucleosides prevent viral replication by inhibiting viral polymerases. However, biological phenomena far exceed our predictions at times. We describe the characteristics of the approved antiviral modified nucleosides from an organic chemistry perspective. Also, based on our experiences 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>Angiotensin Receptor Blockers for COVID-19: Pathophysiological and Pharmacological Considerations About Ongoing and Future Prospective Clinical Trials</strong> - COVID-19 pandemic demands a swift response to find therapeutic tools that effectively reduce morbidity and mortality. Despite initial fears, evidence from retrospective observational studies supports the inhibition of the renin-angiotensin system as an emerging pathway to delay or moderate angiotensin II-driven lung inflammation. This has triggered several prospective clinical trials. In this commentary we provide an overview and analysis of current ongoing clinical trials aimed at evaluating…</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>Epstein-Barr virus lytic replication induces ACE2 expression and enhances SARS CoV-2 pseudotyped virus entry in epithelial cells</strong> - Understanding factors that affect the infectivity of SARS CoV-2 is central to combatting COVID-19. The virus surface spike protein of SARS CoV-2 mediates viral entry into cells by binding to the ACE2 receptor on epithelial cells and promoting fusion. We find that Epstein-Barr virus (EBV) induces ACE2 expression when it enters the lytic replicative cycle in epithelial cells. By using VSV particles pseudotyped with the SARS CoV-2 spike protein, we show that lytic EBV replication enhances…</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>C5aR inhibition of non-immune cells suppresses inflammation and maintains epithelial integrity in SARS-CoV-2-infected primary human airway epithelia</strong> - CONCLUSION: Crucially, we illustrate here for the first time, that targeting the anaphylotoxin receptors C3aR and C5aR in non-immune respiratory cells can prevent intrinsic lung inflammation and tissue damage. This opens up the exciting possibility in the treatment of COVID-19.</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>Hypoxic and pharmacological activation of HIF inhibits SARS-CoV-2 infection of lung epithelial cells</strong> - COVID-19, caused by the novel coronavirus SARS-CoV-2, is a global health issue with more than 2 million fatalities to date. Viral replication is shaped by the cellular microenvironment, and one important factor to consider is oxygen tension, in which hypoxia inducible factor (HIF) regulates transcriptional responses to hypoxia. SARS-CoV-2 primarily infects cells of the respiratory tract, entering via its spike glycoprotein binding to angiotensin-converting enzyme 2 (ACE2). We demonstrate 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>Vaccine-induced immune thrombotic thrombocytopenia (VITT): targeting pathomechanisms with Bruton tyrosine kinase inhibitors</strong> - A series of cases with rare thromboembolic incidents including cerebral sinus vein thrombosis (some of them fatal) and concomitant thrombocytopenia occurring shortly after vaccination with the COVID-19 vaccine AZD1222 (Vaxzevria) has caused significant concern and led to its temporary suspension in many countries. Immediate laboratory efforts in four of these patients have identified a tentative pathomechanism underlying this syndrome termed vaccine-induced prothrombotic immune thrombocytopenia…</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>Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19</strong> - Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association…</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>Structural basis for broad sarbecovirus neutralization by a human monoclonal antibody</strong> - The recent emergence of SARS-CoV-2 variants of concern (VOC) and the recurrent spillovers of coronaviruses in the human population highlight the need for broadly neutralizing antibodies that are not affected by the ongoing antigenic drift and that can prevent or treat future zoonotic infections. Here, we describe a human monoclonal antibody (mAb), designated S2×259, recognizing a highly conserved cryptic receptor-binding domain (RBD) epitope and cross-reacting with spikes from all sarbecovirus…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of SARS-CoV-2 polymerase by nucleotide analogs: a single molecule perspective</strong> - The nucleotide analog Remdesivir (RDV) is the only FDA-approved antiviral therapy to treat infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The physical basis for efficient utilization of RDV by SARS-CoV-2 polymerase is unknown. Here, we characterize the impact of RDV and other nucleotide analogs on RNA synthesis by the polymerase using a high-throughput, single-molecule, magnetic-tweezers platform. The location of the modification in the ribose or in the base dictates…</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 repurposed drug screen identifies compounds that inhibit the binding of the COVID-19 spike protein to ACE2</strong> - Repurposed drugs that block the interaction between the SARS-CoV-2 spike protein and its receptor ACE2 could offer a rapid route to novel COVID-19 treatments or prophylactics. Here, we screened 2701 compounds from a commercial library of drugs approved by international regulatory agencies for their ability to inhibit the binding of recombinant, trimeric SARS-CoV-2 spike protein to recombinant human ACE2. We identified 56 compounds that inhibited binding by <90%, measured the EC (50) of binding…</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>Regulation of the Dimerization and Activity of SARS-CoV-2 Main Protease through Reversible Glutathionylation of Cysteine 300</strong> - SARS-CoV-2 encodes main protease (Mpro), an attractive target for therapeutic interventions. We show Mpro is susceptible to glutathionylation leading to inhibition of dimerization and activity. Activity of glutathionylated Mpro could be restored with reducing agents or glutaredoxin. Analytical studies demonstrated that glutathionylated Mpro primarily exists as a monomer and that a single modification with glutathione is sufficient to block dimerization and loss of activity. Proteolytic…</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>Nitric Oxide to Fight Viral Infections</strong> - Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that has quickly and deeply affected the world, with over 60 million confirmed cases. There has been a great effort worldwide to contain the virus and to search for an effective treatment for patients who become critically ill with COVID-19. A promising therapeutic compound currently undergoing clinical trials for COVID-19 is nitric oxide (NO), which is a free…</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>5-(4-TERT-BUTOXY PHENYL)-3-(4N-OCTYLOXYPHENYL)-4,5-DIHYDROISOXAZOLE MOLECULE (C-I): A PROMISING DRUG FOR SARS-COV-2 (TARGET I) AND BLOOD CANCER (TARGET II)</strong> - The present invention relates to a method ofmolecular docking of crystalline compound (C-I) with SARS-COV 2 proteins and its repurposing with proteins of blood cancer, comprising the steps of ; employing an algorithmto carry molecular docking calculations of the crystalized compound (C-I); studying the compound computationally to understand the effect of binding groups with the atoms of the amino acids on at least four target proteins of SARS-COV 2; downloading the structure of the proteins; removing water molecules, co enzymes and inhibitors attached to the enzymes; drawing the structure using Chem Sketch software; converting the mol file into a PDB file; using crystalized compound (C-I) for comparative and drug repurposing with two other mutated proteins; docking compound into the groove of the proteins; saving format of docked molecules retrieved; and filtering and docking the best docked results. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN320884617">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>USING CLINICAL ONTOLOGIES TO BUILD KNOWLEDGE BASED CLINICAL DECISION SUPPORT SYSTEM FOR NOVEL CORONAVIRUS (COVID-19) WITH THE ADOPTION OF TELECONFERENCING FOR THE PRIMARY HEALTH CENTRES/SATELLITE CLINICS OF ROYAL OMAN POLICE IN SULTANATE OF OMAN</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU320796026">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Peptides and their use in diagnosis of SARS-CoV-2 infection</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU319943278">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A PROCESS FOR SUCCESSFUL MANAGEMENT OF COVID 19 POSITIVE PATIENTS</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU319942709">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IN SILICO SCREENING OF ANTIMYCOBACTERIAL NATURAL COMPOUNDS WITH THE POTENTIAL TO DIRECTLY INHIBIT SARS COV 2</strong> - IN SILICO SCREENING OF ANTIMYCOBACTERIAL NATURAL COMPOUNDS WITH THE POTENTIAL TO DIRECTLY INHIBIT SARS COV 2Insilico screening of antimycobacterial natural compounds with the potential to directly inhibit SARS COV2 relates to the composition for treating SARS-COV-2 comprising the composition is about 0.1 – 99% and other pharmaceutically acceptable excipients. The composition also treats treating SARS, Ebola, Hepatitis-B and Hepatitis–C comprising the composition is about 0.1 – 99% and other pharmaceutically acceptable excipients. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN320777840">link</a></p></li>
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<li><strong>Aronia-Mundspray</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Anordnung zum Versprühen einer Substanz in die menschliche Mundhöhle und/oder in den Rachen oder zum Trinken, dadurch gekennzeichnet, dass die Anordnung eine Flasche mit einer Substanz aufweist, die wenigstens Aroniasaft und eine Alkoholkomponente aufweist und einen Sprühkopf besitzt.
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</p>
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<ul>
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<li><a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=DE321222630">link</a></li>
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</ul></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>INTERFASE ANTIBACTERIANA Y VIRICIDA PARA VENTILACION MECANICA NO INVASIVA</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=ES319943963">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种用于检测新型冠状病毒COVID-19的引物组及试剂盒</strong> - 本发明涉及生物技术领域，特别是涉及一种用于检测冠状病毒的引物组及试剂盒，所述引物组包括以下中的一对或多对：外侧引物对：所述外侧引物对包括如SEQ ID NO:1所示的上游引物F3和如SEQ ID NO:2所示的下游引物B3；内侧引物对：所述内侧引物对包括如SEQ ID NO:3所示的上游引物FIP和如SEQ ID NO:4所示的下游引物BIP；环引物对：所述环引物对包括如SEQ ID NO:5所示的上游引物LF和如SEQ ID NO:6所示的下游引物LB。试剂盒包括所述引物组。本发明在一个管中整合了RT‑LAMP和CRISPR，能依据两次颜色变化检测病毒和各种靶标核酸。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN321132047">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>新冠病毒中和性抗体检测试剂盒</strong> - 本发明提供一种新冠病毒中和性抗体检测试剂盒。所述试剂盒基于BAS‑HTRF技术，主要包含：生物素标记的hACE2、新冠病毒棘突蛋白RBD‑Tag1、能量供体Streptavidin‑Eu cryptate、能量受体MAb Anti‑Tag1‑d2和新冠病毒中和性抗体。本发明将BAS和HTRF两种技术相结合，用于筛选新型冠状病毒中和性抗体，3小时内即可实现筛选，且操作简单，无需经过多次洗板过程。BAS和HTRF联用大大提升了反应灵敏度，且两种体系都能最大限度地减少非特异的干扰，适用于血清样品的检测。该方法可实现高通量检测，对解决大批量样品的新冠病毒中和性抗体的检测具有重要意义。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN321131958">link</a></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Infektionsschutzmaske</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Infektionsschutzmaske (1) zum Schutz vor Übertragung von Infektionskrankheiten mit einer Außen - und einer Innenseite (2,3) sowie Haltemitteln (5) zum Befestigen der Infektionsschutzmaske (1) am Kopf eines Maskenträgers, dadurch gekennzeichnet, dass an der Infektionsschutzmaske (1) mindestens eine Testoberfläche (6) zum Nachweis von Auslösern einer Infektionskrankheit derart angeordnet ist, dass diese bei korrekt angelegter Infektionsschutzmaske (1) mit der Ausatemluft des Maskenträgers unmittelbar in Kontakt gelangt.</p></li>
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<li><a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=DE321222652">link</a></li>
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