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<title>24 September, 2021</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<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>Resilience and Adaptivity Were Strong Correlates of Wellbeing in the Early Stages of the Covid-19 Pandemic</strong> -
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Across the globe, COVID-19 continues to disrupt everyday lives, with serious consequences for individuals’ health and wellbeing. This retrospective, multinational survey study draws upon the Personal Resource Allocation (PRA) framework to explore how various demographic factors, individual differences, and leadership determine the perceived and actual impact of COVID-19 on health (mental, physical) and wellbeing (work, home, general) across five countries: Canada, France, Germany, the United Kingdom, and the United States. Having dependents under 12, working more hours since the onset, and having essential worker status led to better wellbeing outcomes. All three individual differences (adaptivity, resilience, remote work training) were positively related to engagement, with resilience and remote work also relating to better health for these individuals. Lastly, perceptions of COVID impact on mental and physical health had negative consequences for general wellbeing, while effective leadership perceptions predicted work engagement. No differences were found between the five countries. Findings highlight the importance of personal resources in determining the pandemic’s impact on wellbeing.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/ce84n/" target="_blank">Resilience and Adaptivity Were Strong Correlates of Wellbeing in the Early Stages of the Covid-19 Pandemic</a>
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</div></li>
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<li><strong>The DEAD box RNA helicase DDX42 is an intrinsic inhibitor of positive-strand RNA viruses</strong> -
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Genome-wide screens are powerful approaches to unravel new regulators of viral infections. Here, we used a CRISPR/Cas9 screen to reveal new HIV-1 inhibitors. This approach led us to identify the RNA helicase DDX42 as an intrinsic antiviral inhibitor. DDX42 was previously described as a non-processive helicase, able to bind RNA secondary structures such as G- quadruplexes, with no clearly defined function ascribed. Our data show that depletion of endogenous DDX42 significantly increased HIV-1 DNA accumulation and infection in cell lines and primary cells. DDX42 overexpression inhibited HIV-1, whereas a dominant-negative mutant increased infection. Importantly, DDX42 also restricted retrotransposition of LINE-1, infection with other retroviruses and positive-strand RNA viruses, including CHIKV and SARS-CoV-2. However, DDX42 did not inhibit infection with three negative-strand RNA viruses, arguing against a general, unspecific effect on target cells, which was confirmed by RNA-seq analysis. DDX42 was found in the vicinity of viral elements by proximity ligation assays, and cross-linking RNA immunoprecipitation confirmed a specific interaction of DDX42 with RNAs from sensitive viruses. This strongly suggested a direct mode of action of DDX42 on viral ribonucleoprotein complexes. Taken together, our results show for the first time a new and important role of DDX42 in intrinsic antiviral immunity.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.10.28.359356v4" target="_blank">The DEAD box RNA helicase DDX42 is an intrinsic inhibitor of positive-strand RNA viruses</a>
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</div></li>
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<li><strong>Antibodies against type-I Interferon: detection and association with severe clinical outcome in COVID-19 patients</strong> -
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Objectives Impairment of type I interferon (IFN-I) immunity has been reported in critically ill COVID-19 patients. This defect can be explained by the presence of circulating autoantibodies against IFN-I. We set out to improve the detection and the quantification of such antibodies (Abs) in a cohort of severe Covid-19 patients, in an effort to better document the prevalence of these Abs as the pandemics evolves and how they correlate with the clinical course of the disease. Methods Anti-IFN-a Abs was investigated 84 critical COVID-19 patients who were admitted to ICU at the Lyon University Hospital, France with a commercially available kit (Thermo-Fisher). Results Twenty-one patients out of 84 (25%) had anti-IFNa2 Ab above cut-off (>34ng/mL) in sera. A neutralizing activity against IFN-a2 was evidenced in 15 of them, suggesting that 18% of patients were positive for neutralizing anti-IFN-a and -w auto-Abs. In addition, in most of patients with neutralizing IFN-I Abs, we noticed an impairment of the IFN-I response. However, we did not find any difference in terms of clinical characteristics or outcome between critical COVID-19 patients with or without neutralizing anti-IFN-a2 auto-Abs in these conditions. Finally, we detected anti-type I IFN auto-Abs in sera of COVID-19 patients were detected throughout the ICU stay. Conclusions We report that 18% of severe COVID-19 patients were positive for these Anti-Type-I IFN Abs, confirming the detrimental role of these Abs on the antiviral response. Our results further support the use of recombinant type I IFNs not targeted by the auto-Abs (e.g., IFN-b) in COVID-19 patients with an impaired IFN-I response.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.02.21253262v3" target="_blank">Antibodies against type-I Interferon: detection and association with severe clinical outcome in COVID-19 patients</a>
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</div></li>
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<li><strong>Impact of the COVID-19 pandemic on treatment patterns for US patients with metastatic solid cancer</strong> -
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Background: The COVID-19 pandemic has led to delays in patients seeking care for life-threatening conditions; however, its impact on treatment patterns for patients with metastatic cancer is unknown. We assessed the impact of the COVID-19 pandemic on time to treatment initiation (TTI) and treatment selection for patients newly diagnosed with metastatic solid cancer. Methods: We used an electronic health record-derived longitudinal database curated via technology-enabled abstraction to identify 14,136 US patients newly diagnosed with de novo or recurrent metastatic solid cancer between January 1 and July 31 in 2019 or 2020. Patients received care at ~280 predominantly community-based oncology practices. Controlled interrupted time series analyses assessed the impact of the COVID-19 pandemic period (April-July 2020) on TTI, defined as the number of days from metastatic diagnosis to receipt of first-line systemic therapy, and use of myelosuppressive therapy. Results: The adjusted probability of treatment within 30 days of diagnosis [95% confidence interval] was similar across periods: January-March 2019 41.7% [32.2%, 51.1%]; April-July 2019 42.6% [32.4%, 52.7%]; January-March 2020 44.5% [30.4%, 58.6%]; April-July 2020 46.8% [34.6%, 59.0%]; adjusted percentage-point difference-in-differences 1.4% [-2.7%, 5.5%]. Among 5,962 patients who received first-line systemic therapy, there was no association between the pandemic period and use of myelosuppressive therapy (adjusted percentage-point difference-in- differences 1.6% [-2.6%, 5.8%]). There was no meaningful effect modification by cancer type, race, or age. Conclusions: Despite known pandemic-related delays in surveillance and diagnosis, the COVID-19 pandemic did not impact time to treatment initiation or treatment selection for patients with metastatic solid cancers.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.09.22.21263964v1" target="_blank">Impact of the COVID-19 pandemic on treatment patterns for US patients with metastatic solid cancer</a>
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<li><strong>Monoclonal antibodies therapy for Covid-19 - Experiences at a regional hospital.</strong> -
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Applying monoclonal antibodies against Covid-19 is a promising treatment option for avoiding severe outcomes. However, real life data, especially in regional hospitals are still scarce. We here report on our first results with this therapy in a retrospective, observational study. Indeed, compared to a risk-factor matched reference group, hospitalisation time was reduced but survival rate and kinetics of SARS-CoV-2 RT-PCR results remained apparently unaffected.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.09.22.21263488v1" target="_blank">Monoclonal antibodies therapy for Covid-19 - Experiences at a regional hospital.</a>
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</div></li>
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<li><strong>Consequences of COVID-19 vaccine allocation inequity in Chicago</strong> -
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During Chicago9s initial COVID-19 vaccine rollout, the city disproportionately allocated vaccines to zip codes with high incomes and predominantly White populations. However, the impact of this inequitable distribution on COVID-19 outcomes is unknown. This observational study determined the association between zip-code level vaccination rate and COVID-19 mortality in residents of 52 Chicago zip codes. After controlling for age distribution and recovery from infection, a 10% higher vaccination rate by March 28, 2021, was associated with a 39% lower relative risk of death during the peak of the spring wave of COVID-19. Using a difference-in-difference analysis, Chicago could have prevented an estimated 72% of deaths in the least vaccinated quartile of the city (vaccination rates of 17.8 - 26.9%) if it had had the same vaccination rate as the most vaccinated quartile (39.9 - 49.3%). Inequitable vaccine allocation in Chicago likely exacerbated existing racial disparities in COVID-19 mortality.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.09.22.21263984v1" target="_blank">Consequences of COVID-19 vaccine allocation inequity in Chicago</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The impact of heating, ventilation and air conditioning (HVAC) design features on the transmission of viruses, including SARS-CoV-2: an overview of reviews</strong> -
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Objective: Given possible airborne transmission of SARS-CoV-2, an overview of reviews was conducted to understand what is already known from the scientific literature about how virus transmission may be affected by heating, ventilation, and air-conditioning (HVAC) design features in the built environment. Methods: Ovid MEDLINE and Compendex were searched from inception to January 2021. Two reviewers independently screened titles and abstracts and full text of potentially relevant reviews, using a priori inclusion criteria. Inclusion criteria were systematic reviews examining effects of HVAC design features on virus transmission. Two reviewers independently assessed methodological quality using AMSTAR2. Results: Searching identified 361 citations, 45 were potentially relevant, and 7 were included. Reviews were published between 2007 and 2021, and included 47 virus studies. Two earlier reviews (2007, 2016) of 21 studies found sufficient evidence that mechanical ventilation (airflow patterns, ventilation rates) plays a role in airborne transmission; however, both found insufficient evidence to quantify minimum mechanical ventilation requirements. One review (2017) of 9 studies examining humidity and indoor air quality found that influenza virus survival was lowest between 40% and 80% relative humidity; authors noted that ventilation rates were a confounding variable. Two reviews</p></div></li>
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<li>examined mitigation strategies for coronavirus transmission, finding droplet transmission decreased with increasing temperature and relative humidity. One review (2020) identified 14 studies examining coronavirus transmission in air-conditioning systems, finding HVAC systems played a role in virus spread during previous coronavirus outbreaks. One review (2020) examined virus transmission interventions on public ground transportation, finding ventilation and filtration to be effective. Discussion: Seven reviews synthesizing 47 studies demonstrate a role of HVAC in mitigating airborne virus transmission. Ventilation, humidity, temperature, and filtration can play a role in viability and transmission of viruses, including coronaviruses. Recommendations for minimum standards were not possible due to few studies investigating a given HVAC parameter.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.09.22.21263515v1" target="_blank">The impact of heating, ventilation and air conditioning (HVAC) design features on the transmission of viruses, including SARS-CoV-2: an overview of reviews</a>
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<li><strong>An artificial intelligence system for predicting mortality in COVID-19 patients using chest X-rays: a retrospective study</strong> -
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Background: Early prediction of disease severity in COVID-19 patients is essential. Chest X-ray (CXR) is a faster, widely available, and less expensive imaging modality that may be useful in predicting mortality in COVID-19 patients. Artificial Intelligence (AI) may help expedite CXR reading times, and improve mortality prediction. We sought to develop and assess an artificial intelligence system that used chest X-rays and clinical parameters to predict mortality in COVID-19 patients. Methods: A retrospective study was conducted in Ruby Hall Clinic, Pune, India. The study included patients who had a positive real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test for COVID-19 and at least one available chest X-ray at the time of their initial presentation or admission. Features from CXR images and clinical parameters were used to train the Random Forest model. Results: Clinical data from a total of 201 patients was assessed retrospectively. The average age of the cohort was 51.4 ± 14.8 years, with 29.4% of the patients being over the age of 60. The model, which used CXRs and clinical parameters as inputs, had a sensitivity of 0.83 [95% CI: 0.7, 0.95] and a specificity of 0.7 [95% CI: 0.64, 0.77]. The area under the curve (AUC) on receiver operating characteristics (ROC) was increased from 0.74 [95% CI: 0.67, 0.8] to 0.79 [95% CI: 0.72, 0.85] when the model included features of CXRs in addition to clinical parameters. Conclusion: An Artificial Intelligence (AI) model based on CXRs and clinical parameters demonstrated high sensitivity and can be used as a rapid and reliable tool for COVID-19 mortality prediction.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.09.22.21263956v1" target="_blank">An artificial intelligence system for predicting mortality in COVID-19 patients using chest X-rays: a retrospective study</a>
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<li><strong>Deciphering the role of the Pancreatic Secretome in Covid-19 associated Multi-Organ Dysfunctions</strong> -
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Emerging evidence indicates an intricate relationship between the SARS-CoV-2 infection and Multi-Organ Dysfunctions (MODs). Here, we have investigated the role of the Secretome of the SARS-CoV-2 infected pancreas and mechanistically linked it with the multi-organ dysfunction using the scRNA-seq analysis. We found that acinar-specific PRSS2, REG3A, REG1A, SPINK1, and ductal-specific SPP1, MMP7 genes are upregulated in alpha, beta, delta, and mesenchyme cells. Using extensive documented experimental evidence, we validated the association of upregulated pancreatic Secretome with coagulation cascade, complement activation, renin angiotensinogen system dysregulation, endothelial cell injury and thrombosis, immune system dysregulation, and fibrosis. Our finding suggests the influence of upregulated Secretome on multi-organ systems such as Nervous, Cardiovascular, Immune, Digestive, and Urogenital systems. In addition, we report that the secretory proteins IL1B, AGT, ALB, SPP1, CRP, SERPINA1, C3, TFRC, TNFSF10, and MIF are associated with diverse diseases. Thus, suggest the role of the pancreatic Secretome in SARS-CoV-2 associated MODs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.09.22.461447v1" target="_blank">Deciphering the role of the Pancreatic Secretome in Covid-19 associated Multi-Organ Dysfunctions</a>
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<li><strong>Context-aware deconvolution of cell-cell communication with Tensor-cell2cell</strong> -
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Cell interactions determine phenotypes, and intercellular communication is shaped by cellular contexts such as disease state, organismal life stage, and tissue microenvironment. Single-cell technologies measure the molecules mediating cell-cell communication, and emerging computational tools can exploit these data to decipher intercellular communication. However, current methods either disregard cellular context or rely on simple pairwise comparisons between samples, thus limiting the ability to decipher complex cell-cell communication across multiple time points, levels of disease severity, or spatial contexts. Here we present Tensor-cell2cell, an unsupervised method using tensor decomposition, which is the first strategy to decipher context-driven intercellular communication by simultaneously accounting for multiple stages, states, or locations of the cells. To do so, Tensor-cell2cell uncovers context-driven patterns of communication associated with different phenotypic states and determined by unique combinations of cell types and ligand-receptor pairs. We show Tensor-cell2cell can identify multiple modules associated with distinct communication processes (e.g., participating cell-cell and ligand receptor pairs) linked to COVID-19 severities. Thus, we introduce an effective and easy-to-use strategy for understanding complex communication patterns across diverse conditions.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.09.20.461129v1" target="_blank">Context-aware deconvolution of cell- cell communication with Tensor-cell2cell</a>
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<li><strong>Nationally Representative Social Contact Patterns in the United States, August 2020-April 2021</strong> -
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The response to the COVID-19 pandemic in the U.S prompted abrupt and dramatic changes to social contact patterns. Monitoring changing social behavior is essential to provide reliable input data for mechanistic models of infectious disease, which have been increasingly used to support public health policy to mitigate the impacts of the pandemic. While some studies have reported on changing contact patterns throughout the pandemic., few have reported on differences in contact patterns among key demographic groups and none have reported nationally representative estimates. We conducted a national probability survey of US households and collected information on social contact patterns during two time periods: August-December 2020 (before widespread vaccine availability) and March-April 2021 (during national vaccine rollout). Overall, contact rates in Spring 2021 were similar to those in Fall 2020, with most contacts reported at work. Persons identifying as non-White, non-Black, non-Asian, and non-Hispanic reported high numbers of contacts relative to other racial and ethnic groups. Contact rates were highest in those reporting occupations in retail, hospitality and food service, and transportation. Those testing positive for SARS-CoV-2 antibodies reported a higher number of daily contacts than those who were seronegative. Our findings provide evidence for differences in social behavior among demographic groups, highlighting the profound disparities that have become the hallmark of the COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.09.22.21263904v1" target="_blank">Nationally Representative Social Contact Patterns in the United States, August 2020-April 2021</a>
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<li><strong>Risk factors associated with development and persistence of long COVID</strong> -
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Background Long COVID has been a social concern. Though patient characteristics associated with developing long COVID are partially known, those associated with persisting it have not been identified. Methods We conducted a cross- sectional questionnaire survey of patients after COVID-19 recovery who visited the National Center for Global Health and Medicine between February 2020 and March 2021. Demographic and clinical data, and the presence and duration of long COVID were obtained. We identified factors associated with development and persistence of long COVID using multivariate logistic and linear regression analysis, respectively. Results We analyzed 457 of 526 responses (response rate, 86.9%). The median age was 47 years, and 378 patients (84.4%) had mild disease in acute phase. The number of patients with any symptoms after 6 and 12 months after onset or diagnosis were 120 (26.3%) and 40 (8.8%), respectively. Women were at risk for development of fatigue (OR 2.03, 95% CI 1.31-3.14), dysosmia (OR 1.91, 95% CI 1.24-2.93), dysgeusia (OR 1.56, 95% CI 1.02-2.39), and hair loss (OR 3.00, 95% CI 1.77-5.09), and were at risk for persistence of any symptoms (coefficient 38.0, 95% CI 13.3-62.8). Younger age and low body mass index were risk factors for developing dysosmia (OR 0.96, 95% CI 0.94-0.98, and OR 0.94, 95% CI 0.89-0.99, respectively) and dysgeusia (OR 0.98, 95% CI 0.96-1.00, and OR 0.93, 95% CI 0.88-0.98, respectively). Conclusion We identified risk factors for the persistence as well as development of long COVID. Many patients suffer from long-term residual symptoms, even in mild cases.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.09.22.21263998v1" target="_blank">Risk factors associated with development and persistence of long COVID</a>
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<li><strong>Genomic Surveillance in Japan of AY.29—A New Sub-lineage of SARS-CoV-2 Delta Variant with C5239T and T5514C Mutations</strong> -
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In the present study, we report a new sub-lineage of the SARS-CoV-2 Delta variant called AY.29, which has C5239T and T5514C mutations. We investigated the monthly trend of AY.29 in Japan within 11,954 Delta variants downloaded on September 3, 2021. Among the total Japanese Delta variants, the AY.29 sub-lineage accounted for 88.4%. In terms of monthly changes, the sequences became predominant in June, and accounted for 93.2% and 94.2% of the reported sequences in July and August, respectively. Furthermore, the number of Delta variants imported from abroad during the Tokyo 2020 Olympics and Paralympics (held in August 2021) was extremely low. Therefore, the epidemic of the new Delta variant is attributable to a newly occurring mutation in Japan.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.09.20.21263869v2" target="_blank">Genomic Surveillance in Japan of AY.29—A New Sub-lineage of SARS-CoV-2 Delta Variant with C5239T and T5514C Mutations</a>
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<li><strong>Inducible CRISPR activation screen for interferon-stimulated genes identifies OAS1 as a SARS-CoV-2 restriction factor</strong> -
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Interferons establish an antiviral state in responding cells through the induction of hundreds of interferon- stimulated genes (ISGs). ISGs antagonize viral pathogens directly through diverse mechanisms acting at different stages of viral life cycles, and indirectly by modulating cell cycle and promoting programmed cell death. The mechanisms of action and viral specificities for most ISGs remain incompletely understood. To enable the high throughput interrogation of ISG antiviral functions in pooled genetic screens while mitigating the potentially confounding effects of endogenous IFN and potential antiproliferative/proapoptotic ISG activities, we adapted a CRISPR-activation (CRISPRa) system for inducible ISG induction in isogenic cell lines with and without the capacity to respond to IFN. Engineered CRISPRa cell lines demonstrated inducible, robust, and specific gRNA-directed expression of ISGs, which are functional in restricting viral infection. Using this platform, we screened for ISGs that restrict SARS-CoV-2, the causative agent of the COVID-19 pandemic. Results included ISGs previously described to restrict SARS-CoV-2 as well as multiple novel candidate antiviral factors. We validated a subset of candidate hits by complementary targeted CRISPRa and ectopic cDNA expression infection experiments, which, among other hits, confirmed OAS1 as a SARS-CoV-2 restriction factor. OAS1 exhibited strong antiviral effects against SARS-CoV-2, and these effects required OAS1 catalytic activity. These studies demonstrate a robust, high-throughput approach to assess antiviral functions within the ISG repertoire, exemplified by the identification of multiple novel SARS-CoV-2 restriction factors.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.09.22.461286v1" target="_blank">Inducible CRISPR activation screen for interferon-stimulated genes identifies OAS1 as a SARS-CoV-2 restriction factor</a>
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</div></li>
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<li><strong>Identifying The “Core” Transcriptome of SARS-CoV-2 Infected Cells</strong> -
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<div>
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In 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged, causing the COVID-19 pandemic. Consequently, ongoing research has focused on better understanding the mechanisms underlying the symptoms of this disease. Although COVID-19 symptoms span a range of organ systems, the specific changes in gene regulation that lead to the variety of symptoms are still unclear. In our study, we used publicly available transcriptome data from previous studies on SARS-CoV-2 to identify commonly regulated genes across cardiomyocytes, human bronchial epithelial cells, alveolar type II cells, lung adenocarcinoma, human embryonic kidney cells, and patient samples. Additionally, using this common “core” transcriptome, we could identify the genes that were specifically and uniquely differentially regulated in bronchial epithelial cells, embryonic kidney cells, or cardiomyocytes. For example, we found that genes related to cell metabolism were uniquely upregulated in kidney cells, providing us with the first mechanistic clue about specifically how kidney cells may be affected by SARS-CoV-2. Overall, our results uncover connections between the differential gene regulation in various cell types in response to the SARS-CoV-2 infection and help identify targets of potential therapeutics.
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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/10.1101/2021.09.22.461142v1" target="_blank">Identifying The “Core” Transcriptome of SARS-CoV-2 Infected Cells</a>
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</div></li>
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</ul>
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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>Finding Treatments for COVID-19: A Trial of Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Favipiravir; Drug: Monoclonal antibodies; Drug: Ivermectin; Other: No treatment; Drug: Remdesivir<br/><b>Sponsor</b>: University of Oxford<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity Study of AdCLD-CoV19-1: A COVID-19 Preventive Vaccine in Healthy Volunteers</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Biological: AdCLD-CoV19-1<br/><b>Sponsor</b>: <br/>
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Cellid Co., Ltd.<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 Post-Exposure Prophylaxis Study of PF-07321332/Ritonavir in Adult Household Contacts of an Individual With Symptomatic COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: PF-07321332; Drug: Placebo for PF-07321332; Drug: Placebo for Ritonavir; Drug: Ritonavir<br/><b>Sponsor</b>: Pfizer<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>Factors Influencing the COVID-19 Vaccine Immune Response According to Age and Presence or Not of a Past History of COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: COVID-19 vaccine Pfizer (2 doses); Biological: COVID-19 vaccine Pfizer (1 dose); Biological: COVID-19 mRNA Vaccine Moderna (2 doses); Biological: COVID-19 mRNA Vaccine Moderna (1 dose)<br/><b>Sponsors</b>: Centre Hospitalier Universitaire de Saint Etienne; Sanofi Pasteur, a Sanofi Company; Bioaster<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>TThe Safety and Efficacy of SCTV01C in Population Aged ≥18 Years Previously Vaccinated With Inactivated COVID-19 Vaccine.Healthy Population Aged ≥18 Years Previously Vaccinated With Inactivated COVID-19 Vaccine.</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: SCTV01C; Other: Placebo<br/><b>Sponsor</b>: Sinocelltech 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>The Safety and Efficacy of SCTV01C in Population Aged ≥18 Years Previously Vaccinated With Inactivated COVID-19 Vaccine.Healthy Population Aged ≥18 Years Previously Vaccinated With Adenovirus Vectored or mRNA COVID-19 Vaccine.</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: SCTV01C; Other: Placebo<br/><b>Sponsor</b>: Sinocelltech 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>Heterologous Prime-boost Immunization With an Aerosolised Adenovirus Type-5 Vector-based COVID-19 Vaccine (Ad5-nCoV) After Priming With an Inactivated SARS-CoV-2 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: inactive SARS-CoV-2 vaccine (Vero cell); Biological: Low dose aerosolized Ad5-nCoV; Biological: High dose aerosolized Ad5-nCoV<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>A Pilot Study of a PhysiOthErapy-based Tailored Intervention for Long Covid</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Physiotherapy<br/><b>Sponsors</b>: <br/>
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University of Calgary; Alberta Health Services<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>Combined Antihistaminics Therapy in COVID 19 Patients</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Loratadine; Drug: Famotidine<br/><b>Sponsors</b>: Ain Shams University; Nasr City Insurance Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Relate to the Virus That Causes COVID-19, Known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Other: Rapid antigen testing kit<br/><b>Sponsors</b>: <br/>
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Mahidol University; Yuvabadhana foundation; Zero COVID Thailand<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Prevention and Treatment of Patient Before, During, and After Covid-19 Infection</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: AntiCov-220<br/><b>Sponsor</b>: <br/>
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Nguyen Thi Trieu, MD<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Test to Stay in School: COVID-19 Testing Following Exposure in School Communities</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Other: COVID-19 Testing<br/><b>Sponsor</b>: <br/>
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Duke 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>FLuticasone in cOvid Treatment (FLOT)</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: Fluticasone Propionate<br/><b>Sponsor</b>: <br/>
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University of Medicine and Pharmacy at Ho Chi Minh City<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 Baricitinib in Patients With Moderate and Severe COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Baricitinib; Drug: Placebo<br/><b>Sponsor</b>: <br/>
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Incepta Pharmaceuticals 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>Phase 3 Study to Evaluate the Lot Consistency of a Recombinant Coronavirus-Like Particle COVID-19 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: CoVLP formulation<br/><b>Sponsor</b>: <br/>
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Medicago<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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<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>The Use of Biologics During the COVID-19 Pandemic</strong> - During the coronavirus disease 2019 (COVID-19) pandemic, there has been considerable discussion regarding the use of biologics in patients with inflammatory skin conditions, such as psoriasis, hidradenitis suppurativa, and atopic dermatitis. This article discusses clinical trial data, real-world evidence, and guidelines and recommendations for biologics that inhibit tumor necrosis factor, interleukin (IL)-12/23, IL-17, IL-23, and IL-4/13 during the COVID-19 pandemic. Across these inflammatory…</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>Cytometric analysis of patients with COVID-19: what is changed in the second wave?</strong> - CONCLUSIONS: COVID-19 had a less severe impact in patients of the 2nd wave in advanced stages, while the impact appeared more severe in patients of mild and moderate stages, as compared with 1st wave patients. This finding suggests that in COVID-19 patients with milder expression at diagnosis, steroid and azithromycin therapies appear to worsen the immune response against the virus. Furthermore, the cytometric profile may help to drive targeted therapies by monoclonal antibodies to modulate…</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>Discovery of novel oxazole-based macrocycles as anti-coronaviral agents targeting SARS-CoV-2 main protease</strong> - We have discovered a family of synthetic oxazole-based macrocycles to be active against SARS-CoV-2. The synthesis, pharmacological properties, and docking studies of the compounds are reported in this study. The structure of the new macrocycles was confirmed by NMR spectroscopy and mass spectrometry. Compounds 13, 14, and 15a-c were evaluated for their anti-SARS-CoV-2 activity on SARS-COV-2 (NRC-03-nhCoV) virus in Vero-E6 cells. Isopropyl triester 13 and triacid 14 demonstrated superior…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Stem cell-based and mesenchymal stem cell derivatives for coronavirus treatment</strong> - Coronavirus disease 2019 (COVID-19) as one of the diseases pneumonia was first reported in Wuhan, China in December</li>
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</ul>
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<ol start="2019" type="1">
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">COVID-19 is considered the third most common coronavirus among individuals after acute respiratory syndrome (SARS- CoV) and the Middle East respiratory syndrome (MERS-CoV) in the 20^(th) century. Many studies have shown that cell therapy and regenerative medicine approaches have an impressive effect on different dangerous diseases in a way that using a cell-based experiment…</li>
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</ol>
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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>Effective SARS-CoV-2 antiviral activity of hyperbranched polylysine nanopolymers</strong> - The coronavirus pandemic (COVID-19) had spread rapidly since December 2019, when it was first identified in Wuhan, China. As of April 2021, more than 130 million cases have been confirmed, with more than 3 million deaths, making it one of the deadliest pandemics in history. Different approaches must be put in place to confront a new pandemic: community- based behaviours (i.e., isolation and social distancing), antiviral treatments, and vaccines. Although behaviour-based actions have produced…</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>Natural Compounds With Antimicrobial and Antiviral Effect and Nanocarriers Used for Their Transportation</strong> - Due to the increasing prevalence of life-threatening bacterial, fungal and viral infections and the ability of these human pathogens to develop resistance to current treatment strategies, there is a great need to find and develop new compunds to combat them. These molecules must have low toxicity, specific activity and high bioavailability. The most suitable compounds for this task are usually derived from natural sources (animal, plant or even microbial). In this review article, the latest 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>TLR-4 Agonist Induces IFN-γ Production Selectively in Proinflammatory Human M1 Macrophages through the PI3K-mTOR- and JNK-MAPK-Activated p70S6K Pathway</strong> - IFN-γ, a proinflammatory cytokine produced primarily by T cells and NK cells, activates macrophages and engages mechanisms to control pathogens. Although there is evidence of IFN-γ production by murine macrophages, IFN-γ production by normal human macrophages and their subsets remains unknown. Herein, we show that human M1 macrophages generated by IFN-γ and IL-12- and IL-18-stimulated monocyte-derived macrophages (M0) produce significant levels of IFN-γ. Further stimulation of IL-12/IL-18-primed…</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>Semi-continuous propagation of influenza A virus and its defective interfering particles: analyzing the dynamic competition to select candidates for antiviral therapy</strong> - Defective interfering particles (DIPs) of influenza A virus (IAV) are naturally occurring mutants that comprise an internal deletion in one of their eight viral RNA (vRNA) segments, rendering them propagation-incompetent. Upon co- infection with infectious standard virus (STV), DIPs interfere with STV replication through competitive inhibition. Thus, DIPs are proposed as potent antivirals for treatment of the influenza disease. To select corresponding candidates, we studied de novo generation 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>Inhibition of autophagy suppresses SARS-CoV-2 replication and ameliorates pneumonia in hACE2 transgenic mice and xenografted human lung tissues</strong> - Autophagy is thought to be involved in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, how SARS-CoV-2 interferes with the autophagic pathway and whether autophagy contributes to virus infection in vivo is unclear. Here, we identified SARS-CoV-2-triggered autophagy in animal models including the long tailed or crab eating macaque (Macaca fascicularis), hACE2 transgenic mice and xenografted human lung tissues. In Vero E6 and Huh-7 cells, SARS-CoV-2 induces…</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>Research progress of epigallocatechin-3-gallate (EGCG) on anti-pathogenic microbes and immune regulation activities</strong> - At the end of 2019, the COVID-19 virus spread worldwide, infecting millions of people. Infectious diseases induced by pathogenic microorganisms such as the influenza virus, hepatitis virus, and Mycobacterium tuberculosis are also a major threat to public health. The high mortality caused by infectious pathogenic microorganisms is due to their strong virulence, which leads to the excessive counterattack by the host immune system and severe inflammatory damage of the immune system. This paper…</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>Use of Thromboelastography in the Evaluation and Management of Patients With Traumatic Brain Injury: A Systematic Review and Meta-Analysis</strong> - CONCLUSIONS: Thromboelastography and thromboelastography with platelet mapping characterize coagulopathy patterns in traumatic brain injury patients. Abnormal thromboelastography profiles are associated with poor outcomes. Conversely, treatment protocols designed to normalize abnormal parameters may be associated with improved traumatic brain injury patient outcomes. Current quality of evidence in this population is low; so future efforts should evaluate viscoelastic hemostatic assay-guided…</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>Potential natural products that target the SARS-CoV-2 spike protein identified by structure-based virtual screening, isothermal titration calorimetry and lentivirus particles pseudotyped (Vpp) infection assay</strong> - BACKGROUND AND AIM: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells through the binding of the viral spike protein with human angiotensin-converting enzyme 2 (ACE2), resulting in the development of coronavirus disease 2019 (COVID-19). To date, few antiviral drugs are available that can effectively block viral infection. This study aimed to identify potential natural products from Taiwan Database of Extracts and Compounds (TDEC) that may prevent the binding of viral…</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>Correlation of sample-to-cut-off ratio of anti-SARS-CoV-2 IgG antibody chemiluminescent assay with neutralization activity: a prospective multi-centric study in India</strong> - CONCLUSION: Chemiluminescent SARS-CoV-2 IgG assay can be used as a semi-quantitative test, with a cut-off of >8·19S/Co ratio for selecting donors for convalescent plasma therapy and assessing efficacy of vaccination.</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>Synthetic hydrogel nanoparticles for sepsis therapy</strong> - Sepsis is a life-threatening condition caused by the extreme release of inflammatory mediators into the blood in response to infection (e.g., bacterial infection, COVID-19), resulting in the dysfunction of multiple organs. Currently, there is no direct treatment for sepsis. Here we report an abiotic hydrogel nanoparticle (HNP) as a potential therapeutic agent for late-stage sepsis. The HNP captures and neutralizes all variants of histones, a major inflammatory mediator released during sepsis….</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>Characterising proteolysis during SARS-CoV-2 infection identifies viral cleavage sites and cellular targets with therapeutic potential</strong> - SARS-CoV-2 is the causative agent behind the COVID-19 pandemic, responsible for over 170 million infections, and over 3.7 million deaths worldwide. Efforts to test, treat and vaccinate against this pathogen all benefit from an improved understanding of the basic biology of SARS-CoV-2. Both viral and cellular proteases play a crucial role in SARS-CoV-2 replication. Here, we study proteolytic cleavage of viral and cellular proteins in two cell line models of SARS-CoV-2 replication using mass…</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>MACHINE LEARNING TECHNIQUE TO ANALYSE THE CONDITION OF COVID-19 PATIENTS BASED ON THEIR SATURATION LEVELS</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU335054861">link</a></p></li>
|
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A HERB BASED COMPOSITION ANTI VIRAL MEDICINE FOR TREATMENT OF SARS COV 2 AND A METHOD FOR TREATING A PERSON INFECTED BY THE SARS COV 2 VIRUS</strong> - A Herbal composition, viz., PONNU MARUNTHU essentially comprising of ALLUIUM CEPA extract. [concentrated to 30%] 75%, SAPINDUS MUKOROSSI - extract [Optimised] 10%, CITRUS X LIMON - extract in its natural form 05 TRACYSPERMUM AMMI (L) – extract 07%,ROSA HYBRIDA - extract 03%, PONNU MARUNTHU solution 50 ml, or as a capsulated PONNU MARUNTHU can be given to SARS cov2 positive Patients, three times a day that is ½ an hour before food; continued for 3 days to 5 days and further taking it for 2 days if need be there; It will completely cure a person. When the SARS cov2 test shows negative this medicine can be discontinued. This indigenous medicine and method for treating a person inflicted with SARS COV 2 viral infection is quite effective in achieving of much needed remedy for the patients and saving precious lives from the pangs of death and ensuring better health of people. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN334865051">link</a></p></li>
|
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Anti-Sars-Cov-2 Neutralizing Antibodies</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333857732">link</a></p></li>
|
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Expression Vector for Anti-Sars-Cov-2 Neutralizing Antibodies</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333857737">link</a></p></li>
|
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>DEVELOPMENT OF CNN SCHEME FOR COVID-19 DISEASE DETECTION USING CHEST RADIOGRAPH</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333857177">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种检测新型冠状病毒的引物探针组合及其应用</strong> - 本发明提供了一种检测新型冠状病毒的引物探针组合及其应用,所述检测新型冠状病毒的引物探针组合包括特异性扩增并检测2019‑nCoV的ORF1ab基因、核壳蛋白N基因和刺突蛋白S基因N501Y突变位点的特异性引物对和探针。本发明还提供了一种检测新型冠状病毒的试剂盒及其以非疾病诊断和/或治疗为目的的使用方法。本发明所述检测新型冠状病毒的引物探针组合具有良好的特异性与灵敏度,配合优化后的检测体系,可以对待测样本进行快速准确的检测,并可以对整个实验流程进行监控,降低假阳性以及假阴性检测结果的出现概率,具有重要的意义。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN335430482">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-COV-2 BINDING PROTEINS</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333402004">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19胸部CT图像识别方法、装置及电子设备</strong> - 本申请涉及一种COVID‑19胸部CT图像识别方法、装置及电子设备。所述方法获取COVID‑19的胸部CT图像,并针对胸部CT图像的特点,构建新冠肺炎CT识别网络,对该网络进行训练得到COVID‑19胸部CT图像识别模型,并利用该模型对待测CT图像进行分类。采用空洞卷积、深度卷积以及点卷积算子,减少冗余参数;采用并行结构连接方式,实现多尺度特征融合、降低模型复杂度;采用下采样方式,使用最大模糊池化以减少锯齿效应,保持信号的平移不变性;采用通道混洗操作,减少参数量与计算量,提高分类准确率,引入坐标注意力机制,使空间坐标信息与通道信息被关注,抑制不重要的信息,以解决资源匹配问题。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN335069870">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A PROCESS FOR PREPARING MONTELUKAST SODIUM FOR TREATING COVID 19 PATIENTS</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333857132">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IDENTIFICATION OF ANTI-COVID 19 AGENT SOMNIFERINE AS INHIBITOR OF MPRO & ACE2-RBD INTERACTION</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333857079">link</a></p></li>
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