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215 lines
58 KiB
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>19 April, 2022</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 data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The role of exteroceptive and interoceptive awareness in executing socially relevant bodily actions: A naturalistic investigation of greeting behaviour in the UK and Spain</strong> -
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Body awareness is tightly linked to motor action. Non-verbal greetings constitute a behaviour through which an awareness of both socio-cultural habits (exteroceptive awareness) and internal bodily states (interoceptive awareness) play out to influence the structure of action. To establish the effect of culture on non-verbal greeting behaviours, naturalistic observations were carried out in two countries (Britain and Spain) that are purported to exhibit differences in greeting types. Interoceptive awareness (IA) was subsequently measured in a proportion of observed participants (N = 33) who filled in the Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2). As expected, a significant difference in greeting type was observed between British (N = 252) and Spanish (N =</div></li>
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<li>greeters. Scores of greeting intimacy and competency did not differ significantly between Britain and Spain. However, independent of culture, several moderate and strong relationships emerged between selective dimensions of the MAIA-2 and scores of intimacy and competency. Specifically, intimacy and competency scores were positively correlated with the ‘Awareness of Mind-Body Integration’ dimension. Greeting intimacy yielded additional positive relationships with the Not Distracting and Trusting subscales, and a negative relationship with the Not Worrying subscale. These relationships suggest that IA facilitates healthy social approach behaviour as expressed through greetings, irrespective of cultural greeting differences. We discuss IA and greeting behaviour in the context of attachment, consider the clinical implications for social anxiety and the future implications for social interactions in a post-COVID-19 era.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/6jcyd/" target="_blank">The role of exteroceptive and interoceptive awareness in executing socially relevant bodily actions: A naturalistic investigation of greeting behaviour in the UK and Spain</a>
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<li><strong>Pathology and Anticatalytic Treatment of Exacerbated COVID-19</strong> -
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated diseases, which pathophysiology involves the angiotensin-converting enzyme 2 (ACE2) receptor, Toll-like receptor 4 (TLR4) pathway, neuropilin‑1 pathway, inflammasome activation pathway, sterile alpha motif (SAM) and histidine-aspartate domain (HD)-containing protein 1 (SAMHD1) tetramerization pathway, cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway, spike protein/inflammasome-genetic pathway, and immunological memory engram pathway. Therefore, it is necessary to prescribe anticatalytic treatments for type I interferonopathies to alleviate the exacerbated COVID-19 and take the lag time to activate innate or adaptive immune cell reactions.
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🖺 Full Text HTML: <a href="https://osf.io/t9wjz/" target="_blank">Pathology and Anticatalytic Treatment of Exacerbated COVID-19</a>
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<li><strong>Pre-procedural testing improves estimated COVID-19 prevalence and trends</strong> -
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Background: COVID-19 positivity rates reported to the public may provide a distorted view of community trends because they tend to be inflated by high-risk groups, such as symptomatic patients and individuals with known exposures to COVID-19. This positive bias within high-risk groups has also varied over time, depending on testing capability and indications for being tested. In contrast, throughout the pandemic, routine COVID-19 screening tests for elective procedures and operations unrelated to COVID-19 risk have been administered by medical facilities to reduce transmission to medical staffing and other patients. We propose the use of these pre-procedural COVID-19 patient datasets to reduce biases in community trends and better understand local prevalence. Methods: Using patient data from the Maui Medical Group clinic, we analyzed 12,640 COVID-19 test results from May 1, 2020 to March 15, 2021, divided into two time periods corresponding with Maui9s outbreak. Results: Mean positivity rates were 0.1% for the pre-procedural group, 3.9% for the symptomatic group, 4.2% for the exposed group, and 2.0% for the total study population. Post-outbreak, the mean positivity rate of the pre-procedural group was significantly lower than the aggregate group (all other clinic groups combined). The positivity rates of both pre-procedural and aggregate groups increased over the study period, although the pre-procedural group showed a smaller rise in rate. Conclusions: Pre-procedural groups may produce different trends compared to high-risk groups and are sufficiently robust to detect small changes in positivity rates. Considered in conjunction with high-risk groups, pre-procedural marker groups used to monitor understudied, low-risk subsets of a community may improve our understanding of community COVID-19 prevalence and trends.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.13.22273200v1" target="_blank">Pre-procedural testing improves estimated COVID-19 prevalence and trends</a>
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<li><strong>Genetic risk and incident venous thromboembolism in middle-aged and older adults following 1 Covid-19 vaccination</strong> -
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BACKGROUND Covid-19 vaccination has been associated with an increased risk of venous thromboembolism (VTE). However, it is unknown whether genetic predisposition to VTE is associated with an increased risk of thrombosis following vaccination. METHODS Using data from the UK Biobank, which contains in-depth genotyping data and linked vaccination and health outcomes information, we generated a polygenic risk score (PRS) using 299 genetic variants identified from a previous large genome-wide association study. We prospectively assessed associations between PRS and incident VTE after first and the second-dose vaccination separately. We conducted sensitivity analyses stratified by vaccine type (adenovirus- and mRNA-based) and using two historical unvaccinated cohorts. We estimated hazard ratios (HR) for PRS-VTE associations using Cox models. RESULTS Of 359,310 individuals receiving one dose of a Covid-19 vaccine, 160,327 (44.6%) were males, and the mean age at the vaccination date was 69.05 (standard deviation [SD] 8.04) years. After 28- and 90-days follow-up, 88 and 299 individuals developed VTE respectively, equivalent to an incidence rate of 0.88 (95% confidence interval [CI] 0.70 to 1.08) and 0.92 (95% CI 0.82 to 1.04) per 100,000 person-days. The PRS was significantly associated with a higher risk of VTE (HR per 1 SD increase in PRS, 1.41 (95% CI 1.15 to 1.73) in 28 days and 1.36 (95% CI 1.22 to 1.52) in 90 days). Similar associations were found after stratification by vaccine type, in the two-dose cohort and across the historical unvaccinated cohorts. CONCLUSIONS The genetic determinants of post- Covid-19-vaccination VTE are similar to those seen in historical data. This suggests that, at the population level, post-vaccine VTE has similar aetiology to conventional VTE. Additionally, the observed PRS-VTE associations were equivalent for adenovirus- and mRNA-based vaccines.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.14.22273865v1" target="_blank">Genetic risk and incident venous thromboembolism in middle-aged and older adults following 1 Covid-19 vaccination</a>
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<li><strong>Antibody escape and cryptic cross-domain stabilization in the SARS CoV-2 Omicron spike protein</strong> -
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The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the repeated emergence of variants of concern. The Omicron variant has two dominant sub-lineages, BA.1 and BA.2, each with unprecedented numbers of nonsynonymous and indel spike protein mutations: 33 and 29, respectively. Some of these mutations individually increase transmissibility and enhance immune evasion, but their interactions within the Omicron mutational background is unknown. We characterize the molecular effects of all Omicron spike mutations on expression, human ACE2 receptor affinity, and neutralizing antibody recognition. We show that key mutations enable escape from neutralizing antibodies at a variety of epitopes. Stabilizing mutations in the N-terminal and S2 domains of the spike protein compensate for destabilizing mutations in the receptor binding domain, thereby enabling the record number of mutations in Omicron sub-lineages. Taken together, our results provide a comprehensive account of the mutational effects in the Omicron spike protein and illuminate previously unknown mechanisms of how the N-terminal domain can compensate for destabilizing mutations within the more evolutionarily constrained RBD.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.04.18.488614v1" target="_blank">Antibody escape and cryptic cross-domain stabilization in the SARS CoV-2 Omicron spike protein</a>
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<li><strong>Persistent post-COVID-19 smell loss is associated with inflammatory infiltration and altered olfactory epithelial gene expression</strong> -
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Most human subjects infected by SARS-CoV-2 report an acute alteration in their sense of smell, and more than 25% of COVID patients report lasting olfactory dysfunction. While animal studies and human autopsy tissues have suggested mechanisms underlying acute loss of smell, the pathophysiology that underlies persistent smell loss remains unclear. Here we combine objective measurements of smell loss in patients suffering from post-acute sequelae of SARS-CoV-2 infection (PASC) with single cell sequencing and histology of the olfactory epithelium (OE). This approach reveals that the OE of patients with persistent smell loss harbors a diffuse infiltrate of T cells expressing interferon-gamma; gene expression in sustentacular cells appears to reflect a response to inflammatory signaling, which is accompanied by a reduction in the number of olfactory sensory neurons relative to support cells. These data identify a persistent epithelial inflammatory process associated with PASC, and suggests mechanisms through which this T cell-mediated inflammation alters the sense of smell.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.04.17.488474v1" target="_blank">Persistent post-COVID-19 smell loss is associated with inflammatory infiltration and altered olfactory epithelial gene expression</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ocular tropism of SARS-CoV-2 with retinal inflammation through neuronal invasion in animal models</strong> -
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Although ocular manifestations are commonly reported in patients with coronavirus disease 2019 (COVID-19), there is currently no consensus on ocular tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To investigate this, we infected K18-hACE2 mice with SARS-CoV-2 using various routes. We observed ocular manifestation and retinal inflammation with cytokine production in the eyes of intranasally (IN) infected mice. An intratracheal (IT) injection resulted in virus spread from the lungs to the brain and eyes via trigeminal and optic nerves. Ocular and neuronal invasion were confirmed by an intracerebral (IC) infection. Notably, eye-dropped (ED) virus did not infect the lungs and was undetectable with time. Using infectious SARS-CoV-2-mCherry clones, we demonstrated the ocular and neurotropic distribution of the virus in vivo by a fluorescence-imaging system. Evidence for the ocular tropic and neuroinvasive characteristics of SARS-CoV-2 was confirmed in wild-type Syrian hamsters. Our data provides further understanding of the viral transmission; SARS-CoV-2 clinical characteristics; and COVID-19 control procedures.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.04.17.488607v1" target="_blank">Ocular tropism of SARS-CoV-2 with retinal inflammation through neuronal invasion in animal models</a>
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<li>**The SARS-CoV-2 Omicron BA.1 spike G446S potentiates HLA-A*24:02-restricted T cell immunity** -
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Although the Omicron variant of the SARS-CoV-2 virus is resistant to neutralizing antibodies, it retains susceptibility to cellular immunity. Here, we characterized vaccine-induced T cells specific for various SARS-CoV-2 variants and identified HLA-A*24:02-restricted CD8+ T cells that strongly suppressed Omicron BA.1 replication. Mutagenesis analyses revealed that a G446S mutation, located just outside the N-terminus of the cognate epitope, augmented TCR recognition of this variant. In contrast, no enhanced suppression of replication was observed against cells infected with the prototype, Omicron BA.2, and Delta variants that express G446. The enhancing effect of the G446S mutation was lost when target cells were treated with inhibitors of tripeptidyl peptidase II, a protein that mediates antigen processing. These results demonstrate that the G446S mutation in the Omicron BA.1 variant affects antigen processing/presentation and potentiates antiviral activity by vaccine-induced T cells, leading to enhanced T cell immunity towards emerging variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.04.17.488095v1" target="_blank">The SARS-CoV-2 Omicron BA.1 spike G446S potentiates HLA-A*24:02-restricted T cell immunity</a>
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<li><strong>In Silico transcriptional analysis of asymptomatic and severe COVID-19 patients reveals the susceptibility of severe patients to other comorbidities and non-viral pathological conditions</strong> -
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COVID-19 is a severe respiratory disease caused by SARS-CoV-2, a novel human coronavirus. The host response to SARS-CoV-2 infection is not clearly understood. Patients infected with SARS-CoV-2 exhibit heterogeneous intensity of symptoms, i.e., asymptomatic, mild, and severe. Moreover, effects on organs also vary from person to person. These heterogeneous responses pose pragmatic hurdles for implementing appropriate therapy and management of COVID-19 patients. Post-COVID complications pose another major challenge in managing the health of these patients. Thus, understanding the impact of disease severity at the molecular level is vital to delineate the precise host response and management. In the current study, we performed a comprehensive transcriptomics analysis of publicly available seven asymptomatic and eight severe COVID-19 patients. Exploratory data analysis using Principal Component Analysis (PCA) showed the distinct clusters of asymptomatic and severe patients. Subsequently, the differential gene expression analysis using DESeq2 identified 1,224 significantly upregulated genes (logFC>= 1.5, p-adjusted value <0.05) and 268 significantly downregulated genes (logFC<= -1.5, p-adjusted value <0.05) in severe samples in comparison to asymptomatic samples. Eventually, Gene Set Enrichment Analysis (GSEA) of upregulated genes revealed significant enrichment of terms, i.e., anti-viral and anti-inflammatory pathways, secondary infections, Iron homeostasis, anemia, cardiac-related, etc. Gene set enrichment analysis of downregulated genes indicates lipid metabolism, adaptive immune response, translation, recurrent respiratory infections, heme-biosynthetic pathways, etc. In summary, severe COVID-19 patients are more susceptible to other health issues/concerns, non-viral pathogenic infections, atherosclerosis, autoinflammatory diseases, anemia, male infertility, etc. And eventually, these findings provide insight into the precise therapeutic management of severe COVID-19 patients and efficient disease management.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.04.16.488556v1" target="_blank">In Silico transcriptional analysis of asymptomatic and severe COVID-19 patients reveals the susceptibility of severe patients to other comorbidities and non-viral pathological conditions</a>
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<li><strong>Benchmarking the Widely Used Structure-based Binding Affinity Predictors on the Spike-ACE2 Deep Mutational Interaction Set</strong> -
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Since the start of COVID-19 pandemic, a huge effort has been devoted to understanding the Spike-ACE2 recognition mechanism. To this end, two recent deep mutational scanning studies traced the impact of all possible mutations/variants across the Spike-ACE2 interface. Expanding on these studies, we benchmarked four widely used structure-based binding affinity predictors (FoldX, EvoEF1, MutaBind2, SSIPe) and two naive predictors (HADDOCK, UEP) on the variant Spike-ACE2 deep mutational interaction set. Among these approaches, FoldX ranked first with a 64% success rate, followed by EvoEF1 with a 57% accuracy. Upon performing residue-based analyses, we revealed critical algorithmic biases, especially in ranking mutations with increasing/decreasing hydrophobicity/volume. We also showed that the approaches using evolutionary-based terms in their affinity predictions classify most mutations as affinity depleting. These observations suggest plenty of room to improve the conventional affinity predictors for predicting the binding affinity change of the viral host-pathogen system SARS-CoV-2-ACE2. To aid the improvement of the available approaches, we provide our mutant models, together with our benchmarking data at https://github.com/CSB-KaracaLab/ace2-rbd-point-mutation-benchmark .
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.04.18.488633v1" target="_blank">Benchmarking the Widely Used Structure-based Binding Affinity Predictors on the Spike-ACE2 Deep Mutational Interaction Set</a>
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<li><strong>Duration of COVID-19 mRNA Vaccine Effectiveness against Severe Disease</strong> -
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Background: Waning immunity following administration of mRNA based COVID-19 vaccines remains a concern for many health systems. We undertook a study of SARS-CoV-2 infections, with and without requirement for intensive care to shed more light on the duration of vaccine effectiveness for protection against the need for intensive care. Methods: We used a matched case-control study design with the study base being all individuals with first infection with SARS-CoV-2 reported in the State of Qatar between 1 Jan 2021 and 20 Feb 2022. Cases were those requiring intensive care while controls were those who recovered without need for intensive care. Vaccine effectiveness against requiring intensive care and number needed to vaccinate (NNV) to prevent one more case of COVID-19 requiring intensive care were computed for the mRNA (BNT162b2 / mRNA-1273) vaccines. Results: Vaccine effectiveness against requiring intensive care was 59% (95% confidence interval [CI], 50 to 76) between the first and second dose and strengthened to 89% (95% CI, 85 to 92) between the second dose and 4 months post the second dose in persons who received a primary course of the vaccine. There was no waning of vaccine effectiveness in the period from 4 to 12 months after the second dose. Conclusions: This study demonstrates that vaccine effectiveness against requiring intensive care remains robust till at least 12 months after the second dose of mRNA based vaccines.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.12.22273745v1" target="_blank">Duration of COVID-19 mRNA Vaccine Effectiveness against Severe Disease</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Household transmission of SARS-CoV-2 from adult index cases living with and without HIV in South Africa, 2020-2021: a case-ascertained, prospective observational household transmission study</strong> -
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Background In South Africa 19% of the adult population aged 15-49 years are living with HIV (LWH). Few data on the influence of HIV on SARS-CoV-2 household transmission are available. Methods We performed a case-ascertained, prospective household transmission study of symptomatic index SARS-CoV-2 cases LWH and HIV-uninfected adults and their contacts in South Africa. Households were followed up thrice weekly for 6 weeks to collect nasal swabs for SARS-CoV-2 testing. We estimated household cumulative infection risk (HCIR), duration of SARS-CoV-2 positivity (at cycle threshold value<30 as proxy for high viral load), and assessed associated factors. Results We recruited 131 index cases and 457 household contacts. HCIR was 59% (220/373); not differing by index HIV status (60% [50/83] in cases LWH vs 58% [173/293] in HIV-uninfected cases, OR 1.0, 95%CI 0.4-2.3). HCIR increased with index case age (35-59 years: aOR 3.4 95%CI 1.5-7.8 and 60 years or older: aOR 3.1, 95%CI 1.0-10.1) compared to 18-34 years, and contacts age, 13-17 years (aOR 7.1, 95%CI 1.5-33.9) and 18-34 years (aOR 4.4, 95%CI 1.0-18.4) compared to <5 years. Mean positivity duration at high viral load was 7 days (range 2-28), with longer positivity in cases LWH (aHR 0.3, 95%CI 0.1-0.7). Conclusions HIV- infection was not associated with higher HCIR, but cases LWH had longer positivity duration at high viral load. Adults aged >35 years were more likely to transmit, and individuals aged 13-34 to acquire SARS-CoV-2 in the household. Health services must maintain HIV testing with initiation of antiretroviral therapy for those HIV-infected.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.08.22273160v1" target="_blank">Household transmission of SARS- CoV-2 from adult index cases living with and without HIV in South Africa, 2020-2021: a case-ascertained, prospective observational household transmission study</a>
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<li><strong>Effectiveness of a Fourth Dose of COVID-19 Vaccine among Long-Term Care Residents in Ontario, Canada</strong> -
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Background: As of December 30, 2021, Ontario long-term care (LTC) residents who received a third dose of COVID-19 vaccine ≥84 days previously were offered a fourth dose to prevent a surge in COVID-19-related morbidity and mortality due to the Omicron variant. Methods: We used a test-negative design and linked databases to estimate the marginal effectiveness (4 versus 3 doses) and vaccine effectiveness (VE; 2, 3, or 4 doses versus no doses) of mRNA vaccines among Ontario LTC residents aged ≥60 years who were tested for SARS-CoV-2 between December 30, 2021 and March 2, 2022. Outcome measures included any Omicron infection, symptomatic infection, and severe outcomes (hospitalization or death). Results: We included 9,957 Omicron cases and 46,849 test-negative controls. The marginal effectiveness of a fourth dose ≥7 days after vaccination versus a third dose received ≥84 days prior was 40% (95% Confidence Interval[CI], 34-45%) against infection, 63% (95%CI, 51-71%) against symptomatic infection, and 54% (95%CI, 31-70%) against severe outcomes. VE (compared to an unvaccinated group) increased with each additional dose, and for a fourth dose was 65% (95%CI, 60-70%), 87% (95%CI, 81-91%), and 92% (95%CI, 87-95%), against infection, symptomatic infection, and severe outcomes, respectively. Conclusions: Our findings suggest that compared to a third dose received ≥84 days ago, a fourth dose recommendation for LTC residents improved protection against infection, symptomatic infection, and severe outcomes caused by Omicron. Compared to unvaccinated individuals, fourth doses provide strong protection against symptomatic infection and severe outcomes but the duration of protection remains unknown.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.15.22273846v1" target="_blank">Effectiveness of a Fourth Dose of COVID-19 Vaccine among Long-Term Care Residents in Ontario, Canada</a>
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<li><strong>When do persuasive messages on vaccine safety steer COVID-19 vaccine acceptance and recommendations? Behavioral insights from a randomised controlled experiment in Malaysia.</strong> -
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Introduction Vaccine safety is a primary concern among vaccine hesitant individuals. We examined how seven persuasive messages with different frames, all focusing on vaccine safety, influenced Malaysians to take the COVID-19 vaccine, and recommend it to individuals with different health and age profiles (healthy, old age and pre-existing conditions). Methods A randomized controlled experiment was conducted among 5,784 Malaysians who were randomly allocated into 14 experimental arms. They were exposed to one or two messages that promoted COVID-19 vaccination. Interventional messages were applied alone or in combination and compared against a control message. Outcome measures were assessed as intent to both take the vaccine and recommend it to healthy adults, elderly, and people with pre-existing health conditions, before and after message exposure. Changes in intent after message exposure were modeled and we estimate the average marginal effects with respect to changes in the predicted probability of selecting a positive intent for all four outcomes. Results The average baseline proportion of participants with positive intents in each arm to take, and recommend the vaccine to healthy adults, elderly, and people with health conditions was 61.6%, 84.9%, 72.7% and 51.4% respectively. We found that persuasive communication via most of the experimented messages improved recommendation intent to people with a pre-existing health condition, with improvements ranging between 4 to 8 percentage points. In contrast, none of the messages neither significantly improved vaccination intentions, nor recommendations to healthy adults and the elderly. Among this group, we find evidence suggestive of backfiring from messages using negative frames, priming descriptive norms and risky choice frames. Conclusion Persuasive messages aimed at influencing vaccination decisions should incorporate a combination of factors linked to hesitancy. Messages intended to promote recommendation of novel health interventions to unhealthy people should incorporate safety dimensions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.17.22273942v1" target="_blank">When do persuasive messages on vaccine safety steer COVID-19 vaccine acceptance and recommendations? Behavioral insights from a randomised controlled experiment in Malaysia.</a>
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<li><strong>Permissive Omicron breakthrough infections in individuals with binding or neutralizing antibodies to ancestral SARS- CoV-2</strong> -
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Background Breakthrough infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) has occurred in populations with high vaccination rates. These infections are due to sequence variation in the spike protein leading to a reduction in protection afforded by the current vaccines, which are based on the original Wuhan-Hu-1 strain, or by natural infection with pre-Omicron strains. Methods In a longitudinal cohort study, pre-breakthrough infection sera for Omicron breakthroughs (n=12) were analyzed. Assays utilized include a laboratory-developed solid phase binding assay to recombinant spike protein, a commercial assay to the S1 domain of the spike protein calibrated to the World Health Organization (WHO) standard, and a commercial solid-phase surrogate neutralizing activity (SNA) assay. All assays employed spike protein preparations based on sequences from the Wuhan-Hu-1 strain. Participant demographics and clinical characteristics were captured. Results Pre-breakthrough binding antibody (bAB) titers ranged from 1:800-1:51,200 for the laboratory-developed binding assay, which correlated well and agreed quantitatively with the commercial spike S1 domain WHO calibrated assay. SNA was detected in 10/12 (83%) samples. Conclusions Neither high bAB nor SNA were markers of protection from Omicron infection/re-infection. Laboratory tests with antigen targets based on Wuhan-Hu-1 may not accurately reflect the degree of immune protection from variants with significant spike protein differences. Omicron breakthrough infections are likely due to high sequence variation of the spike protein and reflect incomplete immune protection from previous infection with strains that preceded Omicron or with vaccinations based on the original Wuhan-Hu-1 strain.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.17.22273938v1" target="_blank">Permissive Omicron breakthrough infections in individuals with binding or neutralizing antibodies to ancestral SARS-CoV-2</a>
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</div></li>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Functional Capacity in Patients Post Mild COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: Cardiopulmonary exercise test (CPET)<br/><b>Sponsor</b>: Rambam Health Care Campus<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>Circuit Training Program in Post COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Circuit Training Exercise Program; Other: Aerobic Training Exercise Program<br/><b>Sponsor</b>: Riphah International 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>The Effect of Home-based Rehabilitation Program After COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Add-on telerehabilitation and home-based rehabilitation; Behavioral: Home-based rehabilitation alone<br/><b>Sponsor</b>: <br/>
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National Taiwan University Hospital<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, Safety and Immunogenicity Study of COVID-19 Protein Subunit Recombinant Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: SARS-CoV-2 protein subunit recombinant vaccine; Biological: placebo<br/><b>Sponsors</b>: PT Bio Farma; Faculty of Medicine, Universitas Indonesia, Jakarta; Faculty of Medicine, Diponegoro University, Semarang; Faculty of Medicine, Universitas Andalas, Padang; Faculty of Medicine, Universitas Hassanudin, Makassar<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine in Population Aged ≥18 Years</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19<br/><b>Interventions</b>: Biological: SCTV01E; Biological: Comirnaty<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>A Study to Evaluate the Immunogenicity and Safety of Two Recombinant Protein COVID-19 Vaccines in Population Aged ≥18 Years as Booster Vaccines</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: SCTV01C; Biological: SCTV01E; Biological: Sinopharm inactivated COVID-19 vaccine; Biological: mRNA-1273<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>Safety and Efficacy of Enoxaparin and Hydroxychloroquine in COVID-19</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Drug: Enoxaparin, Hydroxychloroquine<br/><b>Sponsor</b>: Beni-Suef University<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>Evaluate the Safety and Immunogenicity of Ad5 COVID-19 Vaccines for Booster Use in Children Aged 6-17 Years.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: 1 Nebulized inhalation for booster groups; Biological: 2 Nebulized inhalation for booster groups; Biological: 3 Nebulized inhalation for booster groups; Biological: 4 Nebulized inhalation for booster groups; Biological: 5 Intramuscular injection for booster groups; Biological: 6 Intramuscular injection for booster groups; Biological: 7 Intramuscular injection for booster groups; Biological: 8 Intramuscular injection for booster groups; Biological: 9 Intramuscular injection for booster groups; Biological: 10 Intramuscular injection for booster groups; Biological: 11 Nebulized inhalation for booster groups; Biological: 12 Nebulized inhalation for booster groups; Biological: 13 Nebulized inhalation for booster groups; Biological: 14 Nebulized inhalation for booster groups; Biological: 15 Intramuscular injection for booster groups; Biological: 16 Intramuscular injection for booster groups; Biological: 17 Intramuscular injection for booster groups; Biological: 18 Intramuscular injection for booster groups; Biological: 19 Intramuscular injection for booster groups; Biological: 20 Intramuscular injection for booster groups; Biological: 21 Nebulized inhalation for primary groups; Biological: 22 Nebulized inhalation for primary groups; Biological: 23 Nebulized inhalation for primary groups; Biological: 24 Nebulized inhalation for primary groups<br/><b>Sponsor</b>: <br/>
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Seventh Medical Center of PLA General 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>Non-inferiority Trial on Treatments in Early COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Sotrovimab; Drug: Tixagevimab Cilgavimab; Drug: Nirmatrelvir Ritonavir<br/><b>Sponsors</b>: Azienda Ospedaliera Universitaria Integrata Verona; Agenzia Italiana del Farmaco; Azienda Sanitaria-Universitaria Integrata di Udine<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>Neutralizing Power of Anti-SARS-CoV-2 (Anti-COVID-19) Serum Antibodies</strong> - <b>Conditions</b>: COVID-19; SARS CoV 2 Infection<br/><b>Intervention</b>: <br/>
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Other: Collection of biological samples<br/><b>Sponsor</b>: Centre Hospitalier Régional d’Orléans<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>Immunogenicity and Safety Study of Recombinant Two-Component COVID-19 Vaccine (CHO Cell)(ReCOV)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant two-component COVID-19 vaccine (CHO cell); Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsor</b>: Jiangsu Rec- Biotechnology 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>Immunogenicity，Safety and Cross - Immune Response With the Strains of the Booster Immunization Using an Inactivated COVID-19 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Inactivated COVID-19 Vaccine<br/><b>Sponsor</b>: Sinovac Research and Development 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>SARS-CoV-2 Specific Immune Response After COVID-19 Vaccination in Cancer Patients</strong> - <b>Conditions</b>: COVID-19; Cancer<br/><b>Intervention</b>: Biological: CoronaVac vaccine<br/><b>Sponsors</b>: National Cancer Institute, Thailand; Mahidol University<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>Safety and Immunogenicity of Recombinant SARS-CoV-2 Spike Protein Vaccine (CHO Cell) for the Prevention of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: ZR-202-CoV; Other: Placebo<br/><b>Sponsors</b>: Shanghai Zerun Biotechnology Co.,Ltd; Walvax Biotechnology 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>Interleukine 6 (IL6) Assay for Predicting Failure of Spontaneous Breathing in Patients With COVID-19 Acute Respiratory Distress Syndrome</strong> - <b>Condition</b>: COVID-19 Acute Respiratory Distress Syndrome<br/><b>Interventions</b>: <br/>
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Biological: IL6 assessment; Biological: CRP and PCT assessment<br/><b>Sponsor</b>: <br/>
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Centre Hospitalier Henri Duffaut - Avignon<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A rapid bead-based assay for screening of SARS-CoV-2 neutralizing antibodies</strong> - Quantitative determination of neutralizing antibodies against Severe Acute Respiratory Syndrome Corona Virus-2 (SARS- CoV-2) is paramount in immunodiagnostics, vaccine efficacy testing, and immune response profiling among the vaccinated population. Cost-effective, rapid, easy-to-perform assays are essential to support the vaccine development process and immunosurveillance studies. We describe a bead-based screening assay for S1-neutralization using recombinant fluorescent proteins of hACE2 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>Anti-breast cancer effects of phytochemicals: primary, secondary, and tertiary care</strong> - Breast cancer incidence is actually the highest one among all cancers. Overall breast cancer management is associated with challenges considering risk assessment and predictive diagnostics, targeted prevention of metastatic disease, appropriate treatment options, and cost-effectiveness of approaches applied. Accumulated research evidence indicates promising anti-cancer effects of phytochemicals protecting cells against malignant transformation, inhibiting carcinogenesis and metastatic spread,…</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>Multi-omics insights into host-viral response and pathogenesis in Crimean-Congo hemorrhagic fever viruses for novel therapeutic target</strong> - The pathogenesis and host-viral interactions of the Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) are convoluted and not well evaluated. Application of the multi-omics system biology approaches, including biological network analysis in elucidating the complex host-viral response, interrogates the viral pathogenesis. The present study aimed to fingerprint the system-level alterations during acute CCHFV-infection and the cellular immune responses during productive CCHFV-replication in…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A meta-analysis result: Uneven influences of season, geo-spatial scale and latitude on relationship between meteorological factors and the COVID-19 transmission</strong> - Meteorological factors have been confirmed to affect the COVID-19 transmission, but current studied conclusions varied greatly. The underlying causes of the variance remain unclear. Here, we proposed two scientific questions: (1) whether meteorological factors have a consistent influence on virus transmission after combining all the data from the studies;</li>
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</ul>
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<ol start="2" type="1">
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">whether the impact of meteorological factors on the COVID-19 transmission can be influenced by season, geospatial scale and latitude. We…</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>An endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the coronavirus disease-19 (COVID-19) pandemic, was identified in late 2019 and caused >5 million deaths by February 2022. To date, targeted antiviral interventions against COVID-19 are limited. The spectrum of SARS-CoV-2 infection ranges from asymptomatic to fatal disease. However, the reasons for varying outcomes to SARS-CoV-2 infection are yet to be elucidated. Here we show that an endogenously activated interferon…</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>Impact of Remdesivir Incorporation along the Primer Strand on SARS-CoV-2 RNA-Dependent RNA Polymerase</strong> - Remdesivir was the first antiviral drug that received emergency use authorization from the United States Food and Drug Administration and is now formally approved to treat COVID-19. Remdesivir is a nucleotide analogue that targets the RNA- dependent RNA polymerase (RdRp) of coronaviruses, including SARS-CoV-2. The solution of multiple RdRp structures has been one of the main axes of research in the race against the SARS-CoV-2 virus. Several hypotheses of the mechanism of inhibition of RdRp by…</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>Clinically observed deletions in SARS-CoV-2 Nsp1 affect its stability and ability to inhibit translation</strong> - Nonstructural protein 1 (Nsp1) of SARS-CoV-2 inhibits host cell translation through an interaction between its C-terminal domain and the 40S ribosome. The N-terminal domain (NTD) of Nsp1 is a target of recurring deletions, some of which are associated with altered COVID-19 disease progression. Here, we characterize the efficiency of translational inhibition by clinically observed Nsp1 deletion variants. We show that a frequent deletion of residues 79-89 severely reduces the ability of Nsp1 to…</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 Carbohydrate Binding Agents neutralize SARS-CoV-2 by inhibiting binding of the spike protein to ACE2</strong> - Developing strategies against the SARS-CoV-2 is currently a main research subject. SARS-CoV-2 infects host cells by binding to human ACE2 receptors. Both, virus and ACE2, are highly glycosylated, and exploiting glycans of the SARS-CoV-2 envelope as binding sites for ACE2 represents a virus strategy for attacking the human host. We report here that a family of mannose-binding synthetic carbohydrate binding agents (CBAs) inhibit SARS-CoV-2 infection, showing broad neutralizing activity vs. several…</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 Inhibit SARS-CoV-2 nsp13 Unwinding and ATPase Enzyme Activities</strong> - SARS-CoV-2 infection is still spreading worldwide, and new antiviral therapies are an urgent need to complement the approved vaccine preparations. SARS-CoV-2 nps13 helicase is a validated drug target participating in the viral replication complex and possessing two associated activities: RNA unwinding and 5’-triphosphatase. In the search of SARS-CoV-2 direct antiviral agents, we established biochemical assays for both SARS-CoV-2 nps13-associated enzyme activities and screened both in silico 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>Hit Expansion of a Noncovalent SARS-CoV-2 Main Protease Inhibitor</strong> - Inhibition of the SARS-CoV-2 main protease (M^(pro)) is a major focus of drug discovery efforts against COVID-19. Here we report a hit expansion of non-covalent inhibitors of M^(pro). Starting from a recently discovered scaffold (The COVID Moonshot Consortium. Open Science Discovery of Oral Non-Covalent SARS-CoV-2 Main Protease Inhibitor Therapeutics. bioRxiv 2020.10.29.339317) represented by an isoquinoline series, we searched a database of over a billion compounds using a cheminformatics…</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>Anti-COVID-19 potential of <em>Azadirachta indica</em> (Neem) leaf extract</strong> - COVID-19 is caused by infection with the "severe acute respiratory syndrome coronavirus-2″ (i.e., SARS-CoV-2). This is an enveloped virus having a positive sense, single-stranded RNA genome; like the two earlier viruses SARS-CoV and the Middle East respiratory syndrome (MERS) virus. COVID-19 is unique in that, in the severe case, it has the propensity to affect multiple organs, leading to multiple organ distress syndrome (MODS), and causing high morbidity and mortality in the extreme case. 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>Too hard to die: Exercise training mediates specific and immediate SARS-CoV-2 protection</strong> - Several mechanisms may explain how exercise training mechanistically confers protection against coronavirus disease 2019 (COVID-19). Here we propose two new perspectives through which cardiorespiratory fitness may protect against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Physical exercise-activated adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling induces endothelial nitric oxide (NO) synthase (eNOS), increases NO bio- availability, and inhibits…</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>Rifampicin for COVID-19</strong> - Vaccinations for coronavirus disease-2019 (COVID-19) have begun more than a year before, yet without specific treatments available. Rifampicin, critically important for human medicine (World Health Organization’s list of essential medicines), may prove pharmacologically effective for treatment and chemoprophylaxis of healthcare personnel and those at higher risk. It has been known since 1969 that rifampicin has a direct selective antiviral effect on viruses which have their own RNA polymerase…</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>Selective covalent targeting of SARS-CoV-2 main protease by enantiopure chlorofluoroacetamide</strong> - The coronavirus disease 2019 (COVID-19) pandemic has necessitated the development of antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The main protease (M^(pro)) is a promising target for COVID-19 treatment. Here, we report an irreversible SARS-CoV-2 M^(pro) inhibitor possessing chlorofluoroacetamide (CFA) as a warhead for the covalent modification of M^(pro). Ugi multicomponent reaction using chlorofluoroacetic acid enabled the rapid synthesis of dipeptidic…</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 a new generation of angiotensin receptor blocking drugs: receptor mechanisms and in silico binding to enzymes relevant to covid-19</strong> - The discovery and facile synthesis of a new class of sartan-like arterial antihypertensive drugs (angiotensin receptor blockers [ARBs]), subsequently referred to as “bisartans” is reported. In vivo results and complementary molecular modelling presented in this communication indicate bisartans may be beneficial for the treatment of not only heart disease, diabetes, renal dysfunction, and related illnesses, but possibly COVID-19. Bisartans are novel bis-alkylated imidazole sartan derivatives…</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>SYSTEM FOR MONITORING COVID-19 PATIENTS USING A VIRTUAL TELEPRESENCE ROBOT</strong> - Attached Separately - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN356991740">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MASCARA FACIAL PARA LA INHALACION DE SUBSTANCIAS NEBULIZADAS, CON SISTEMA DE ASPIRACION INCORPORADO</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=ES355538276">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MACHINE LEARNING TECHNIQUE TO ANALYZE THE WORK PRESSURE OF PARAMEDICAL STAFF DURING COVID 19</strong> - Machine learning technique to analyse the work pressure of paramedical staff during covid 19 is the proposed invention that focuses on identifying the stress levels of paramedical staff. The invention focuses on analysing the level of stress that is induced on the paramedical staff especially during pandemic. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN353347401">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种吡咯烷酮中间体的合成方法</strong> - 本发明涉及药物中间体合成技术领域，尤其是一种吡咯烷酮中间体的合成方法，包括以下步骤：化合物1溶液和有机锂试剂溶液泵入连续反应器，反应生成锂氢交换中间体，再泵入卤代乙腈与中间态发生反应生成化合物2；化合物2用固定床反应装置内进行氢化反应，后处理得到化合物3；将化合物3的溶液和氨水溶液泵入连续反应器生成酰胺化合物4；化合物4和脱水剂使用恒流泵泵入连续化反应器，生成化合物5或其氨基上有保护基的中间体；应用串联连续反应技术，将传统釜式数步反应改进为连续化工艺，解决了传统釜式反应的放大效应问题，降低了含金属试剂以及高压氢化等危险反应的安全风险进而避免了超低温反应釜和高压氢化釜等设备，提高了生产效率。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN357081864">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一株表达新冠病毒S1蛋白单克隆抗体杂交瘤细胞系及中和活性抗体</strong> - 本发明属于细胞工程与免疫学领域，具体涉及一株表达新冠病毒S1蛋白单克隆抗体杂交瘤细胞系及中和活性抗体。本发明筛选获得一株能高效稳定分泌表达新冠病毒S1蛋白单克隆抗体的杂交瘤细胞系以及其分泌的新冠病毒S1蛋白单克隆抗体；利用普通细胞培养皿培养本发明的重组杂交瘤细胞系，产量可达10mg/L，且纯度能达90%以上；本发明的单抗具有高中和活性，单抗浓度为0.00103μg/mL时即可抑制50％以上新冠假病毒活性，是目前所报告的新冠单抗中和活性最佳的。本发明提供的杂交瘤细胞系或单克隆抗体在新冠病毒的血清学检测、制备新冠病毒感染的试剂或药物及制备新冠病毒抗原或抗体检测的试剂中具有重要的应用价值。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN357081918">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>基于SARS-CoV-2的S蛋白的疫苗及其用途</strong> - 本公开提供了基于SARS‑CoV‑2的S蛋白的疫苗及其用途，并具体涉及重组SARS‑CoV‑2刺突蛋白(S蛋白)及编码其的mRNA和DNA。本公开还涉及包含编码重组S蛋白的DNA序列的重组质粒。本公开的重组质粒经转录得到mRNA，其包含SEQ ID NO.12所示的序列。本公开进一步涉及包含前述mRNA的mRNA‑载体颗粒例如脂质纳米颗粒(LNP)和组合物例如疫苗组合物。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN356073372">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>CBD Covid 19 Protection</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU353359094">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种双价可电离脂质化合物、组合物及其应用</strong> - 本发明涉及核酸药物递送技术领域，特别是关于一种双价可电离脂质化合物、组合物及其应用。本发明提供多种可以递送核酸药物的可电离阳离子脂质，具备较强的可设计性、可生物降解性及高效的体内外转染效率，由其组成的脂质纳米递送系统用于递送mRNA，在细胞水平上，优于目前上市的产品，并且在动物水平也具有良好的递送效率，可以作为核酸药物的递送新的方法，促进核酸药物的发展。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN356073405">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种双价可电离脂质化合物、组合物及其应用</strong> - 本发明涉及核酸药物递送技术领域，特别是关于一种双价可电离脂质化合物、组合物及其应用。本发明提供多种可以递送核酸药物的可电离阳离子脂质，具备较强的可设计性、可生物降解性及高效的体内外转染效率，由其组成的脂质纳米递送系统用于递送mRNA，在细胞水平上，优于目前上市的产品，并且在动物水平也具有良好的递送效率，可以作为核酸药物的递送新的方法，促进核酸药物的发展。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN356073406">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>新冠肺炎CT图像分割方法及终端设备</strong> - 本发明公开了一种新冠肺炎CT图像分割方法及终端设备，方法包括获取待分割新冠肺炎CT图像；将该图像输入至训练好的分割模型中，得到新冠肺炎病灶区域的图像；其中分割模型包括依次连接的多个下采样模块和下采样模块对应的上采样模块；每个采样模块均包括依次连接的第一提取单元和第二提取单元；上述两个提取单元的卷积模块均为结构重参数化卷积模块。本发明的结构重参数化卷积模块为训练时使用多分支结构，加强模型表达能力，推理时使用单路结构，加快推理速度，快速得出诊断结果。同时，为从不同尺度特征图中学习分层表示，加强模型对图像边缘信息提取，并使梯度更快回流，上采样每一侧输出都连接混合损失函数，实现图像的像素级分割。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN356073393">link</a></p></li>
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