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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>Old minds, new marketplaces: How evolved psychological mechanisms trigger mismatched consumption responses</strong> -
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The national lockdowns related to the COVID-19 pandemic revealed that few days of limited travel and consumption are enough to improve air quality worldwide, thus contributing to sustainable development. But under regular circumstances, shoppers are reluctant to change their consumption habits for the common good. Why is that? To answer this question, we delineate proximate and ultimate explanations of consumer behavior. The former—pervasive in the marketing literature—focuses on how behaviors occur, whereas the latter—underrepresented in marketing thought and practice—focuses on why human evolution fashioned such behaviors. The evolutionary approach to consumer behavior considers both explanations. We draw on the fundamental motives framework, which explains why certain behaviors—often irrational at first glance—solve specific adaptive problems found in ancestral and modern societies. Finally, we show how evolutionary mismatches—where mechanisms solving adaptive problems in ancient times produce maladaptive outcomes nowadays—distort optimal and sustainable decision-making in three domains: voting, buying status-signaling goods, and food consumption. We conclude by showing how to apply the law of law's leverage to facilitate cost-effective policymaking.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/sp8zm/" target="_blank">Old minds, new marketplaces: How evolved psychological mechanisms trigger mismatched consumption responses</a>
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<li><strong>SARS-CoV-2 spike protein arrested in the closed state induces potent neutralizing responses</strong> -
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The majority of SARS-CoV-2 vaccines in use or in advanced clinical development are based on the viral spike protein (S) as their immunogen. S is present on virions as pre-fusion trimers in which the receptor binding domain (RBD) is stochastically open or closed. Neutralizing antibodies have been described that act against both open and closed conformations. The long-term success of vaccination strategies will depend upon inducing antibodies that provide long-lasting broad immunity against evolving, circulating SARS-CoV-2 strains, while avoiding the risk of antibody dependent enhancement as observed with other Coronavirus vaccines. Here we have assessed the results of immunization in a mouse model using an S protein trimer that is arrested in the closed state to prevent exposure of the receptor binding site and therefore interaction with the receptor. We compared this with a range of other modified S protein constructs, including representatives used in current vaccines. We found that all trimeric S proteins induce a long-lived, strongly neutralizing antibody response as well as T-cell responses. Notably, the protein binding properties of sera induced by the closed spike differed from those induced by standard S protein constructs. Closed S proteins induced more potent neutralising responses than expected based on the degree to which they inhibit interactions between the RBD and ACE2. These observations suggest that closed spikes recruit different, but equally potent, virus-inhibiting immune responses than open spikes, and that this is likely to include neutralizing antibodies against conformational epitopes present in the closed conformation. Together with their improved stability and storage properties we suggest that closed spikes may be a valuable component of refined, next-generation vaccines.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.14.426695v1" target="_blank">SARS-CoV-2 spike protein arrested in the closed state induces potent neutralizing responses</a>
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<li><strong>Mutation rates and selection on synonymous mutations in SARS-CoV-2</strong> -
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The COVID-19 pandemic has seen an unprecedented response from the sequencing community. Leveraging the sequence data from more than 140,000 SARS-CoV-2 genomes, we study mutation rates and selective pressures affecting the virus. Understanding the processes and effects of mutation and selection has profound implications for the study of viral evolution, for vaccine design, and for the tracking of viral spread. We highlight and address some common genome sequence analysis pitfalls that can lead to inaccurate inference of mutation rates and selection, such as ignoring skews in the genetic code, not accounting for recurrent mutations, and assuming evolutionary equilibrium. We find that two particular mutation rates, G[->]U and C[->]U, are similarly elevated and considerably higher than all other mutation rates, causing the majority of mutations in the SARS-CoV-2 genome, and are possibly the result of APOBEC and ROS activity. These mutations also tend to occur many times at the same genome positions along the global SARS-CoV-2 phylogeny (i.e., they are very homoplasic). We observe an effect of genomic context on mutation rates, but the effect of the context is overall limited. While previous studies have suggested selection acting to decrease U content at synonymous sites, we bring forward evidence suggesting the opposite.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.14.426705v1" target="_blank">Mutation rates and selection on synonymous mutations in SARS-CoV-2</a>
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<li><strong>Natural SARS-CoV-2 infection in kept ferrets, Spain</strong> -
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We found SARS-CoV-2 RNA in 6 of 71 ferrets (8.4%) and isolated the virus from one rectal swab. Natural SARS-CoV-2 infection does occur in kept ferrets, at least under circumstances of high viral circulation in the human population. However, small ferret collections are probably unable to maintain prolonged virus circulation.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.14.426652v1" target="_blank">Natural SARS-CoV-2 infection in kept ferrets, Spain</a>
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<li><strong>Anti-CoVid19 plasmid DNA vaccine induces a potent immune response in rodents by Pyro-drive Jet Injector intradermal inoculation</strong> -
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There is an urgent need to limit and stop the worldwide coronavirus disease 2019 (COVID-19) pandemic via quick development of efficient and safe vaccination methods. Plasmid DNA vaccines are one of the most remarkable vaccines that can be developed in a short term. pVAX1-SARS-CoV2-co, which is a plasmid DNA vaccine, was designed to express severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein. The produced antibodies lead to Immunoreactions against S protein, anti-receptor-binding-domain, and neutralizing action of pVAX1-SARS-CoV2-co, as confirmed in a previous study. To promote the efficacy of the pVAX1-SARS-CoV2-co vaccine, a pyro-drive jet injector (PJI) was employed. PJI is an injection device that can adjust the injection pressure depending on various target tissues. Intradermally-adjusted PJI demonstrated that pVAX1-SARS-CoV2-co vaccine injection caused a strong production of anti-S protein antibodies, triggered immunoreactions and neutralizing actions against SARS-CoV-2. Moreover, a high dose of pVAX1-SARS-CoV2-co intradermal injection via PJI did not cause any serious disorders in the rat model. Finally, virus infection challenge in mice, confirmed that intradermally immunized (via PJI) mice were potently protected from COVID-19 infection. Thus, pVAX1-SARS-CoV2-co intradermal injection via PJI is a safe and promising vaccination method to overcome the COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.13.426436v1" target="_blank">Anti-CoVid19 plasmid DNA vaccine induces a potent immune response in rodents by Pyro-drive Jet Injector intradermal inoculation</a>
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<li><strong>Surveillance of genetic diversity and evolution in locally transmitted SARS-CoV-2 in Pakistan during the first wave of the COVID-19 pandemic</strong> -
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Surveillance of genetic diversity in the SARS-CoV-2 is extremely important to detect the emergence of more infectious and deadly strains of the virus. In this study, we monitored mutational events in the SARS-CoV-2 genome through whole genome sequencing. The samples (n=48) were collected from the hot spot regions of the metropolitan city Karachi, Pakistan during the four months (May 2020 to August 2020) of first wave of the COVID-19 pandemic. The data analysis highlighted 122 mutations, including 120 single nucleotide variations (SNV), and 2 deletions. Among the 122 mutations, there were 71 singletons, and 51 recurrent mutations. A total of 16 mutations, including 5 nonsynonymous mutations, were detected in spike protein. Notably, the spike protein missense mutation D614G was observed in 31 genomes. The phylogenetic analysis revealed majority of the genomes (36) classified as B lineage, where 2 genomes were from B.6 lineage, 5 genomes from B.1 ancestral lineage and remaining from B.1 sub-lineages. It was noteworthy that three clusters of B.1 sub-lineages were observed, including B.1.36 lineage (10 genomes), B.1.160 lineage (11 genomes), and B.1.255 lineage (5 genomes), which represent independent events of SARS-CoV-2 transmission within the city. The sub-lineage B.1.36 had higher representation from the Asian countries and the UK, B.1.160 correspond to the European countries with highest representation from the UK, Denmark, and lesser representation from India, Saudi Arabia, France and Switzerland, and the third sub-lineage (B.1.255) correspond to the USA. Collectively, our study provides meaningful insight into the evolution of SARS-CoV-2 lineages in spatio-temporal local transmission during the first wave of the pandemic.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.13.426548v1" target="_blank">Surveillance of genetic diversity and evolution in locally transmitted SARS-CoV-2 in Pakistan during the first wave of the COVID-19 pandemic</a>
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<li><strong>The lethal triad: SARS-CoV-2 Spike, ACE2 and TMPRSS2. Mutations in host and pathogen may affect the course of pandemic.</strong> -
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Variants of SARS-CoV-2 have been identified rapidly after the beginning of pandemic. One of them, involving the spike protein and called D614G, represents a substantial percentage of currently isolated strains. While research on this variant was ongoing worldwide, on December 20th 2020 the European Centre for Disease Prevention and Control reported a Threat Assessment Brief describing the emergence of a new variant of SARS-CoV-2, named B.1.1.7, harboring multiple mutations mostly affecting the Spike protein. This viral variant has been recently associated with a rapid increase in COVID-19 cases in South East England, with alarming implications for future virus transmission rates. Specifically, of the nine amino acid replacements that characterize the Spike in the emerging variant, four are found in the region between the Fusion Peptide and the RBD domain (namely the already known D614G, together with A570D, P681H, T716I), and one, N501Y, is found in the Spike Receptor Binding Domain-Receptor Binding Motif (RBD-RBM). In this study, by using in silico biology, we provide evidence that these amino acid replacements have dramatic effects on the interactions between SARS-CoV-2 Spike and the host ACE2 receptor or TMPRSS2, the protease that induces the fusogenic activity of Spike. Mostly, we show that these effects are strongly dependent on ACE2 and TMPRSS2 polymorphism, suggesting that dynamics of pandemics are strongly influenced not only by virus variation but also by host genetic background.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.12.426365v1" target="_blank">The lethal triad: SARS-CoV-2 Spike, ACE2 and TMPRSS2. Mutations in host and pathogen may affect the course of pandemic.</a>
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<li><strong>A highly thermotolerant, trimeric SARS-CoV-2 receptor binding domain derivative elicits high titers of neutralizing antibodies</strong> -
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The Receptor Binding Domain of SARS-CoV-2 is the primary target of neutralizing antibodies. We fused our previously described, highly thermotolerant glycan engineered monomeric RBD to a heterologous non-immunogenic trimerization domain derived from cartilage matrix protein. The protein was expressed at a good yield of ~80-100 mg/liter in Expi293 cells, as well as in both CHO and HEK293 stable cell lines. The designed trimeric RBD was observed to form homogeneous disulfide-linked trimers. When lyophilized, the trimer possessed remarkable functional stability to transient thermal stress of upto 100 {degrees}C and was stable to long term storage of over 4 weeks at 37 {degrees}C. Two immunizations with an AddaVax adjuvanted formulation elicited antibodies with high endpoint neutralizing titers against replicative virus with geometric mean titers of ~1114 and 1940 in guinea pigs and mice respectively. In pseudoviral assays, corresponding titers were ~3600 and ~16050, while the corresponding value for human convalescent sera was 137. Similar results were obtained with an Alhydrogel, CpG combination adjuvant. The same immunogen was expressed in Pichia pastoris, but this formed high molecular weight aggregates and elicited much lower ACE2 competing antibodies than mammalian cell expressed protein. The excellent thermotolerance, high yield, and robust immunogenicity of such trimeric RBD immunogens suggest that they are a promising modality to combat COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.13.426626v1" target="_blank">A highly thermotolerant, trimeric SARS-CoV-2 receptor binding domain derivative elicits high titers of neutralizing antibodies</a>
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<li><strong>Susceptibility of white-tailed deer (Odocoileus virginianus) to SARS-CoV-2</strong> -
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The origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing the global coronavirus disease 19 (COVID-19) pandemic, remains a mystery. Current evidence suggests a likely spillover into humans from an animal reservoir. Understanding the host range and identifying animal species that are susceptible to SARS-CoV-2 infection may help to elucidate the origin of the virus and the mechanisms underlying cross-species transmission to humans. Here we demonstrated that white-tailed deer (Odocoileus virginianus), an animal species in which the angiotensin converting enzyme 2 (ACE2) - the SARS-CoV-2 receptor - shares a high degree of similarity to humans, are highly susceptible to infection. Intranasal inoculation of deer fawns with SARS-CoV-2 resulted in established subclinical viral infection and shedding of infectious virus in nasal secretions. Notably, infected animals transmitted the virus to non-inoculated contact deer. Viral RNA was detected in multiple tissues 21 days post-inoculation (pi). All inoculated and indirect contact animals seroconverted and developed neutralizing antibodies as early as day 7 pi. The work provides important insights into the animal host range of SARS-CoV-2 and identifies white-tailed deer as a susceptible wild animal species to the virus.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.13.426628v1" target="_blank">Susceptibility of white-tailed deer (Odocoileus virginianus) to SARS-CoV-2</a>
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<li><strong>N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2</strong> -
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SARS-CoV-2 entry into host cells is orchestrated by the spike (S) glycoprotein that contains an immunodominant receptor-binding domain (RBD) targeted by the largest fraction of neutralizing antibodies (Abs) in COVID-19 patient plasma. Little is known about neutralizing Abs binding to epitopes outside the RBD and their contribution to protection. Here, we describe 41 human monoclonal Abs (mAbs) derived from memory B cells, which recognize the SARS-CoV-2 S N-terminal domain (NTD) and show that a subset of them neutralize SARS-CoV-2 ultrapotently. We define an antigenic map of the SARS-CoV-2 NTD and identify a supersite recognized by all known NTD-specific neutralizing mAbs. These mAbs inhibit cell-to-cell fusion, activate effector functions, and protect Syrian hamsters from SARS-CoV-2 challenge. SARS-CoV-2 variants, including the 501Y.V2 and B.1.1.7 lineages, harbor frequent mutations localized in the NTD supersite suggesting ongoing selective pressure and the importance of NTD-specific neutralizing mAbs to protective immunity.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.14.426475v1" target="_blank">N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2</a>
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<li><strong>Big Five personality traits and COVID-19 precautionary behaviors among older adults in Europe</strong> -
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Objectives: Taking precaution against COVID-19 is important particularly among older adults who have a greater risk for severe illness if infected. We examined whether Big Five personality traits are associated with COVID-19 precautionary behaviors among older adults in Europe. Method: We used data from the Survey of Health, Aging and Retirement in Europe (N=34 801). Personality was self-reported in 2017 using the BFI-10 inventory. COVID-19 precautionary behaviors – wearing a mask, limiting social contacts, and keeping distance to others – were assessed in the summer of 2020 through self-reports. Associations between personality and precautionary behaviors were examined with multilevel random-intercept logistic regression models. The models were adjusted for age, gender, educational attainment, and country of residence. Results: Higher conscientiousness, neuroticism, and openness were associated with a greater likelihood of wearing a face mask. Higher neuroticism was associated with a greater likelihood of limiting social contacts, and higher agreeableness with a lower likelihood of limiting social contacts. Higher conscientiousness was associated with a greater likelihood of keeping distance to others. The associations between personality and practicing precautionary behaviors were relatively weak. Discussion: Among older adults, taking COVID-19 precautionary behaviors was most consistently related to higher conscientiousness and neuroticism, suggesting that precautionary behaviors may be motivated by multiple psychological differences.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/rvbjf/" target="_blank">Big Five personality traits and COVID-19 precautionary behaviors among older adults in Europe</a>
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<li><strong>The Mental Health of Latinx Adults in the United States During the Coronavirus Pandemic: A Snapshot of Anxiety, Depression, and Posttraumatic Stress Symptoms</strong> -
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The current study documented levels of anxiety, depression, posttraumatic stress, and COVID-19 fears and impacts among Latinxs in the U.S. during the COVID-19 pandemic. Participants of this cross-sectional study were 388 Latinx adults who completed an online survey between June and November 2020. Almost half of participants showed clinical levels of anxiety and depression and more than a quarter of participants showed clinical levels of posttraumatic stress. Latinxs reported on average 22 types of negative pandemic life impacts. Group differences based on gender, educational attainment, income, vulnerability to COVID-19, and essential worker status were found for mental health symptoms. Severity of COVID-19 fears and negative life impact counts were related to gender, nativity, educational attainment, vulnerability to COVID-19, and insurance status. Specific Latinx groups experienced greater levels of psychological distress during the pandemic. Further examination of risk and protective factors is needed for communities of color.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/uq5y2/" target="_blank">The Mental Health of Latinx Adults in the United States During the Coronavirus Pandemic: A Snapshot of Anxiety, Depression, and Posttraumatic Stress Symptoms</a>
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<li><strong>"Help! I Need Somebody": Music as a Global Resource for Obtaining Wellbeing Goals in Times of Crisis</strong> -
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Music can reduce stress and anxiety, enhance positive mood, and facilitate social bonding. However, little is known about the role of music and related personal or cultural (individualistic versus collectivistic) variables in maintaining wellbeing during times of stress and social isolation as imposed by the COVID-19 crisis. In an online questionnaire, administered in 11 countries (Argentina, Brazil, China, Colombia, Italy, Mexico, the Netherlands, Norway, Spain, the UK and USA, N = 5619), participants rated the relevance of wellbeing goals during the pandemic, and the effectiveness of different activities in obtaining these goals. Music was found to be the most effective activity for three out of five wellbeing goals: enjoyment, venting negative emotions, and self-connection. For diversion, music was equally good as entertainment, while it was second best to create a sense of togetherness, after socialization. This result was evident across different countries and gender, with minor effects of age on specific goals, and a clear effect of the importance of music in people’s lives. Cultural effects were generally small and surfaced mainly in the use of music to obtain a sense of togetherness. Interestingly, culture moderated the use of negatively valenced and nostalgic music for those higher in distress.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/frcqn/" target="_blank">"Help! I Need Somebody": Music as a Global Resource for Obtaining Wellbeing Goals in Times of Crisis</a>
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<li><strong>A Novel Abnormality Annotation Database for COVID-19 Affected Frontal Lung X-rays</strong> -
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Purpose: To advance the usage of CXRs as a viable solution for efficient COVID-19 diagnostics by providing large-scale annotations of the abnormalities in frontal CXRs in the BIMCV-COVID19 database, and to provide a robust evaluation mechanism to facilitate its usage. Materials and Methods: We provide the abnormality annotations in frontal CXRs by creating bounding boxes. The frontal CXRs are a part of the existing BIMCV-COVID19+ database. We also define four different protocols for robust evaluation of semantic segmentation and classification algorithms. Finally, we benchmark the defined protocols and report the results using popular deep learning models as a part of this study. Results: For semantic segmentation, Mask-RCNN performs the best among all the models with a DICE score of 0.43. For classification, we observe that MobileNetv2 yields the best results for 2-class and 3-class classification. We also observe that deep models report a lower performance for classifying other classes apart from the COVID class. Conclusion: By making the annotated data and protocols available to the scientific community, we aim to advance the usage of CXRs as a viable solution for efficient COVID-19 diagnostics. This large-scale data will be useful for ML algorithms and can be used for learning radiological patterns observed in COVID-19 patients. Further, the protocols will facilitate ML practitioners for unified large-scale evaluation of their algorithms.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.01.07.21249323v2" target="_blank">A Novel Abnormality Annotation Database for COVID-19 Affected Frontal Lung X-rays</a>
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<li><strong>OpenSAFELY NHS Service Restoration Observatory 1: describing trends and variation in primary care clinical activity for 23.3 million patients in England during the first wave of COVID-19</strong> -
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Background The COVID-19 pandemic has disrupted healthcare activity globally. The NHS in England stopped most non-urgent work by March 2020, but later recommended that services should be restored to near-normal levels before winter where possible. The authors are developing the OpenSAFELY NHS Service Restoration Observatory, using data to describe changes in service activity during COVID-19, and reviewing signals for action with commissioners, researchers and clinicians. Here we report phase one: generating, managing, and describing the data. Objective To describe the volume and variation of coded clinical activity in English primary care across 23.8 million patients records, taking respiratory disease and laboratory procedures as key examples. Methods Working on behalf of NHS England we developed an open source software framework for data management and analysis to describe trends and variation in clinical activity across primary care EHR data on 23.8 million patients; and conducted a population cohort-based study to describe activity using CTV3 coding hierarchy and keyword searches from January 2019-September 2020. Results Much activity recorded in general practice declined to some extent during the pandemic, but largely recovered by September 2020, with some exceptions. There was a large drop in coded activity for commonly used laboratory tests, with broad recovery to pre-pandemic levels by September. One exception was blood coagulation tests such as International Normalised Ratio (INR), with a smaller reduction (median tests per 1000 patients in 2020: February 8.0; April 6.2; September 7.0). The overall pattern of recording for respiratory symptoms was less affected, following an expected seasonal pattern and classified as no change from the previous year. Respiratory tract infections exhibited a sustained drop compared with pre-pandemic levels, not returning to pre-pandemic levels by September 2020. Various COVID-19 codes increased through the period. We observed a small decline associated with high level codes for long-term respiratory conditions such as chronic obstructive pulmonary disease (COPD) and asthma. Asthma annual reviews experienced a small drop but since recovered, while COPD annual reviews remain below baseline. Conclusions We successfully delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. The COVD-19 pandemic led to a substantial change in healthcare activity. Most laboratory tests showed substantial reduction, largely recovering to near-normal levels by September 2020, with some important tests less affected. Records of respiratory infections decreased with the exception of codes related to COVID-19, whilst activity of other respiratory disease codes was mixed. We are expanding the NHS Service Restoration Observatory in collaboration with clinicians, commissioners and researchers and welcome feedback.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.01.06.21249352v2" target="_blank">OpenSAFELY NHS Service Restoration Observatory 1: describing trends and variation in primary care clinical activity for 23.3 million patients in England during the first wave of COVID-19</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>Dexamethasone for COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: Dexamethasone<br/><b>Sponsor</b>: University of Oklahoma<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 (HD)IVACOV Trial (The High-Dose IVermectin Against COVID-19 Trial)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Ivermectin 0.6mg/kg/day; Drug: Ivermectin 1.0mg/kg/day; Drug: Placebo; Drug: Hydroxychloroquine<br/><b>Sponsor</b>: Corpometria Institute<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of ORTD-1 in Patients Hospitalized With COVID-19 Related Pneumonia</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: ORTD-1 low dose; Drug: ORTD-1 mid dose; Drug: ORTD-1 high dose; Other: Vehicle control<br/><b>Sponsor</b>: Oryn Therapeutics, LLC<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>Rapid Diagnosis of COVID-19 by Chemical Analysis of Exhaled Air</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Diagnostic Test: Performance evaluation (sensitivity and specificity) for COVID-19 diagnosis of the Vocus PTR-TOF process<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>IMUNOR® Preparation in the Prevention of COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: IMUNOR<br/><b>Sponsor</b>: University Hospital Ostrava<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>Clinical Experimentation With Tenofovir Disoproxyl Fumarate and Emtricitabine for COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Vitamin C 500 MG Oral Tablet; Drug: Tenofovir disoproxyl fumarate 300 MG Oral Tablet; Drug: Tenofovir disoproxyl fumarate 300 MG plus emtricitabine 200 MG Oral Tablet<br/><b>Sponsors</b>: Universidade Federal do Ceara; Conselho Nacional de Desenvolvimento Científico e Tecnológico; São José Hospital for Infectious Diseases - HSJ; Central Laboratory of Public Health of Ceará - Lacen-CE<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 Study to Evaluate MVC-COV1901 Vaccine Against COVID-19 in Adult</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>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Safety and Efficacy of Pyronaridine-artesunate (Pyramax® or Artecom®)in COVID-19 Patients</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Artecom® (pyronaridine-artesunate); Drug: Placebo<br/><b>Sponsor</b>: Shin Poong Pharmaceutical Co. Ltd.<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 to Evaluate the Safety, Tolerability, and Efficacy of BGE-175 in Participants ≥ 60 Years of Age and Hospitalized With Coronavirus Disease 2019 (COVID-19) That Are Not in Respiratory Failure</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: BGE-175; Other: Placebo<br/><b>Sponsor</b>: BioAge Labs, 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>Efficacy of Ramdicivir and Baricitinib for the Treatment of Severe COVID 19 Patients</strong> - <b>Conditions</b>: Covid19; Covid-19 ARDS<br/><b>Interventions</b>: Drug: Remdesivir; Drug: Baricitinib; Drug: Tocilizumab<br/><b>Sponsors</b>: M Abdur Rahim Medical College and Hospital; First affiliated Hospital Xi'an Jiaoting University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antiseptic Mouth Rinses to Reduce Salivary Viral Load in COVID-19 Patients</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Betadine© bucal 100 mg/ml; Drug: Oximen® 3%; Drug: Clorhexidine Dental PHB©; Drug: Vitis Xtra Forte©; Drug: Distilled Water<br/><b>Sponsors</b>: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana; Hospital Universitario Fundación Jiménez Díaz; Hospital Universitario General de Villalba; Hospital Universitario Infanta Elena; Hospital Universitario Virgen de la Arrixaca; Hospital Clínico Universitario de Valencia; Dentaid SL<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effect of Deep Breathing Exercise on Dyspnea, Anxiety and Quality of Life in Patients Treated for COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Deep Breathing Exercise with Triflo<br/><b>Sponsor</b>: Ankara 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>RU Anti-SARS-CoV-2 (COVID-19) mAbs in Healthy Volunteers</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Biological: C144-LS and C-135-LS<br/><b>Sponsor</b>: Rockefeller University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pilot Study of Cefditoren Pivoxil in COVID-19 Patients With Mild to Moderate Pneumonia</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Drug: Cefditoren pivoxil 400mg<br/><b>Sponsor</b>: Meiji Pharma Spain S.A.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Influence of Covid-19 on the Audio-vestibular System</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Diagnostic Test: Audio-Vestibular evaluation<br/><b>Sponsor</b>: HaEmek Medical Center, Israel<br/><b>Not yet 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>Complement Inhibition in Severe COVID-19 Acute Respiratory Distress Syndrome</strong> - Most children with COVID-19 have asymptomatic or mild illness. Those who become critically ill suffer from acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). The rapid deterioration of lung function has been linked to microangiopathic and immune-mediated processes seen in the lungs of adult patients with COVID-19. The role of complement-mediated acute lung injury is supported by animal models of SARS-CoV, evaluation of lung tissue in those who died from COVID-19 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>Intravenous Immunoglobulin may Reverse Multisystem Inflammation in COVID-19 Pneumonitis and Guillain-Barre Syndrome</strong> - CONCLUSION: While the use of hyperimmune globulin requires a tedious job of collection from convalescent patients with verified and adequate titers, the use of IVIg could be an easier option to modulate the immune storm and faster recovery in SARS-CoV-2.</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 proposed molecular mechanism for pathogenesis of severe RNA-viral pulmonary infections</strong> - Background: Certain riboviruses can cause severe pulmonary complications leading to death in some infected patients. We propose that DNA damage induced-apoptosis accelerates viral release, triggered by depletion of host RNA binding proteins (RBPs) from nuclear RNA bound to replicating viral sequences. Methods: Information theory-based analysis of interactions between RBPs and individual sequences in the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), Influenza A (H3N2), HIV-1, 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>Inhibition of coronavirus infection by a synthetic STING agonist in primary human airway system</strong> - The newly emerged severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) coronavirus initiated a pneumonia outbreak (COVID-19) that rapidly spread worldwide and quickly became a public health emergency of international concern; However to date, except Remdesivir, there are no clinically approved specific or effective medicines to prevent or treat COVID-19. Therefore, the development of novel treatments against coronavirus infections caused by the current SARS-CoV-2 virus, as well as other...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Quercetin as a potential treatment for COVID-19-induced acute kidney injury: Based on network pharmacology and molecular docking study</strong> - Kidneys are one of the targets for SARS-CoV-2, it is reported that up to 36% of patients with SARS-CoV-2 infection would develop into acute kidney injury (AKI). AKI is associated with high mortality in the clinical setting and contributes to the transition of AKI to chronic kidney disease (CKD). Up to date, the underlying mechanisms are obscure and there is no effective and specific treatment for COVID-19-induced AKI. In the present study, we investigated the mechanisms and interactions between...</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>Pharmacokinetic modelling to estimate intracellular favipiravir ribofuranosyl-5'-triphosphate exposure to support posology for SARS-CoV-2</strong> - CONCLUSION: This modelling approach has several important limitations that are discussed in the main text of the manuscript. However, the simulations indicate that despite rapid clearance of the parent drug from plasma, sufficient intracellular FAVI-RTP may be maintained across the dosing interval because of its long intracellular half-life. Population average intracellular FAVI-RTP concentrations are estimated to maintain the Km for the SARS-CoV-2 polymerase for 3 days following 800 mg BID...</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>Fever, Diarrhea, and Severe Disease Correlate with High Persistent Antibody Levels against SARS-CoV-2</strong> - Lasting immunity will be critical for overcoming the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, factors that drive the development of high titers of anti-SARS-CoV-2 antibodies and how long those antibodies persist remain unclear. Our objective was to comprehensively evaluate anti-SARS-CoV-2 antibodies in a clinically diverse COVID-19 convalescent cohort at defined time points to determine if anti-SARS-CoV-2...</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>MVA Vector Vaccines Inhibit SARS CoV-2 Replication in Upper and Lower Respiratory Tracts of Transgenic Mice and Prevent Lethal Disease</strong> - Replication-restricted modified vaccinia virus Ankara (MVA) is a licensed smallpox vaccine and numerous clinical studies investigating recombinant MVAs (rMVAs) as vectors for prevention of other infectious diseases have been completed or are in progress. Two rMVA COVID-19 vaccine trials are at an initial stage, though no animal protection studies have been reported. Here, we characterize rMVAs expressing the S protein of CoV-2. Modifications of full length S individually or in combination...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 spike downregulates tetherin to enhance viral spread</strong> - The antiviral restriction factor, tetherin, blocks the release of several different families of enveloped viruses, including the Coronaviridae . Tetherin is an interferon-induced protein that forms parallel homodimers between the host cell and viral particles, linking viruses to the surface of infected cells and inhibiting their release. We demonstrate that SARS-CoV-2 downregulates tetherin to aid its release from cells, and investigate potential proteins involved in this process. Loss of...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 induces human plasmacytoid pre-dendritic cell diversification via UNC93B and IRAK4</strong> - Several studies have analyzed antiviral immune pathways in late-stage severe COVID-19. However, the initial steps of SARS-CoV-2 antiviral immunity are poorly understood. Here, we have isolated primary SARS-CoV-2 viral strains, and studied their interaction with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. We show that pDC are not productively infected by SARS-CoV-2. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Repurposing of Biologic and Targeted Synthetic Anti-Rheumatic Drugs in COVID-19 and Hyper-Inflammation: A Comprehensive Review of Available and Emerging Evidence at the Peak of the Pandemic</strong> - Coronavirus disease 2019 (COVID-19) is a condition caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severe cases of COVID-19 result in acute respiratory distress syndrome and death. A detrimental, hyper-inflammatory immune response with excess release of cytokines is the main driver of disease development and of tissue damage in these patients. Thus, repurposing of biologic agents and other pharmacological inhibitors of cytokines used for the treatment of various...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Non-steroidal anti-inflammatory drugs dampen the cytokine and antibody response to SARS-CoV-2 infection</strong> - Identifying drugs that regulate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its symptoms has been a pressing area of investigation during the coronavirus disease 2019 (COVID-19) pandemic. Nonsteroidal anti-inflammatory drugs (NSAIDs), which are frequently used for the relief of pain and inflammation, could modulate both SARS-CoV-2 infection and the host response to the virus. NSAIDs inhibit the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), which...</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>APOBEC3s: history of an antiviral and mutagenic protein family</strong> - The innate immune response is nonspecific and constitutes the first line of defense against infections by pathogens, mainly by enabling their elimination by phagocytosis or apoptosis. In immune cells, this response is characterized, amongst others, by the synthesis of restriction factors, a class of proteins whose role is to inhibit viral replication. Among them, the proteins of the APOBEC3 (Apolipoprotein B mRNA-editing Enzyme Catalytic polypeptide-like 3 or A3) family are major antiviral...</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>Observations on the use of Bruton's tyrosine kinase inhibitors in SAR-CoV-2 and cancer</strong> - Bruton's tyrosine kinase (BTK) inhibitors, drugs utilized in cancer, are being repurposed for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (COVID-19). Recently, BTK inhibitors acalabrutinib and ibrutinib have been found to protect against pulmonary injury in a small group of patients infected with SARS-CoV-2. The high levels of pro-inflammatory cytokines found in the circulation of COVID-19 patients with severe lung disease suggest the involvement of the innate immune system in...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>On the role of bacterial metalloproteases in COVID-19 associated cytokine storm</strong> - The cytokine release syndrome or cytokine storm, which is the hyper-induction of inflammatory responses has a central role in the mortality rate of COVID-19 and some other viral infections. Interleukin-6 (IL-6) is a key player in the development of cytokine storms. Shedding of interleukin-6 receptor (IL-6Rα) results in the accumulation of soluble interleukin-6 receptors (sIL-6R). Only relatively few cells express membrane-bound IL-6Rα. However, sIL-6R can act on potentially all cells and organs...</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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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 CLASSIFICATION RECOGNITION METHOD BASED ON CT IMAGES OF LUNGS</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU314054415">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A traditional Chinese medicine composition for COVID-19 and/or influenza and preparation method thereof</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313300659">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Covid 19 - Chewing Gum</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313269181">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>STOCHASTIC MODEL METHOD TO DETERMINE THE PROBABILITY OF TRANSMISSION OF NOVEL COVID-19</strong> - The present invention is directed to a stochastic model method to assess the risk of spreading the disease and determine the probability of transmission of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN313339294">link</a></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Fahrzeuglüftungssystem und Verfahren zum Betreiben eines solchen Fahrzeuglüftungssystems</strong> -
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</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Die Erfindung betrifft ein Fahrzeuglüftungssystem (1) zum Belüften einer Fahrgastzelle (2) eines Fahrzeugs (3), mit einem Umluftpfad (5). Die Erfindung ist gekennzeichnet durch eine wenigstens abschnittsweise in einen Umluftansaugbereich (4) des Umluftpads (5) hineinreichende Sterilisationseinrichtung (6), wobei die Sterilisationseinrichtung (6) dazu eingerichtet ist von einem aus der Fahrgastzelle (2) entnommenen Luftstrom getragene Schadstoffe zu inaktivieren und/oder abzutöten.</p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=DE313868337">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313251184">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313251182">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>"AYURVEDIC PROPRIETARY MEDICINE FOR TREATMENT OF SEVERWE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2."</strong> - AbstractAyurvedic Proprietary Medicine for treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)In one of the aspect of the present invention it is provided that Polyherbal combinations called Coufex (syrup) is prepared as Ayurvedic Proprietary Medicine , Aqueous Extracts Mixing with Sugar Syrup form the following herbal aqueous extract coriandrum sativum was used for the formulation of protek.Further another Polyherbal combination protek as syrup is prepared by the combining an aqueous extract of the medicinal herbs including Emblica officinalis, Terminalia chebula, Terminalia belerica, Aegle marmelos, Zingiber officinale, Ocimum sanctum, Adatoda zeylanica, Piper lingum, Andrographis panivulata, Coriandrum sativum, Tinospora cordiofolia, cuminum cyminum,piper nigrum was used for the formulation of Coufex. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN312324209">link</a></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mund-Nasen-Bedeckung</strong> -
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</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Mund-Nasen-Bedeckung (1), wobei die Mund-Nasen-Bedeckung (1) mindestens an einem Ohr eines Trägers magnetisch befestigbar ist.</p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=DE313866760">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Haptens, hapten conjugates, compositions thereof and method for their preparation and use</strong> - A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU311608060">link</a></p></li>
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