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<title>04 October, 2023</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>Moral Judgments Impact Perceived Risks from COVID-19 Exposure</strong> -
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The COVID-19 pandemic has created enormously difficult decisions for individuals trying to navigate both the risks of the pandemic and the demands of everyday life. Good decision making in such scenarios can have life and death consequences. For this reason, it is important to understand what drives risk assessments during a pandemic, and, in particular, to investigate the ways that these assessments might deviate from ideal risk assessments. Two studies (N = 841) investigate risk judgments related to COVID-19. The results indicate that risk judgments are sensitive to factors unrelated to the objective risks of infection. In particular, activities that are morally justified are perceived as safer while those that might subject people to blame, or culpability, are seen as riskier.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/59s2g/" target="_blank">Moral Judgments Impact Perceived Risks from COVID-19 Exposure</a>
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<li><strong>Prevalence and factors associated with fear of COVID-19 in military personnel during the second epidemic wave in Peru</strong> -
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There is few research in military members that provided protection and security during the COVID-19 crisis. We aimed to determine the prevalence and factors associated with fear of COVID-19 in military members. A cross-sectional study was conducted between November 02 and 09, 2021, during the second wave of the COVID-19 pandemic in the region of Lambayeque, Peru. The outcome was fear of COVID-19, measured with the Fear of COVID-19 Scale. The association with resilience (abbreviated CD-RISC), food insecurity (HFIAS), physical activity (IPAQ-S), eating disorder (EAT-26), and other socio-labor variables were assessed. Of 525 participants, the median age was 22, 95.8% were male, and 19.2% experienced fear of COVID-19. A higher prevalence of fear of COVID-19 was associated with age (PR=1.03; 95% CI: 1.01-1.06), religion (PP=2.05; 95% CI: 1.04-4.05), eating disorder (PR=2.95; 95% CI: 1.99-4.36), and having a relative with mental disorder (PR=2.13; 95% CI: 1.09-4.17). Overweight (PR=0.58; 95% IC: 0.37-0.90) and a high level of resilience (PR=0.63; 95% IC: 0.43-0.93) were associated with a lower prevalence of fear of COVID-19. Two out of ten military personnel were afraid of COVID-19. We recommend special attention to the factors associated with the development of suicide risk in military personnel.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.03.23296474v1" target="_blank">Prevalence and factors associated with fear of COVID-19 in military personnel during the second epidemic wave in Peru</a>
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</div></li>
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<li><strong>Mendelian Randomization Reveals the Role of HMGCR in Pulmonary Arterial Hypertension Treatment, Independent of LDL Cholesterol Concentration</strong> -
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Introduction: Specific lipid-reducing therapeutics, including statins, are known for mitigating cardiovascular diseases due to their comprehensive benefits including anti-inflammatory properties, antioxidative stress response, and enhancement of endothelial function. The objective of our study was to determine the causative impact of lipid-reducing agents (HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitor) on the outcomes of pulmonary hypertension via a two-sample Mendelian randomization (MR) analysis. Methods: Two types of genetic tools were employed to estimate the exposure to lipid-lowering drugs, comprising expression quantitative trait loci of the drug9s target genes and genetic variations close to or within the target genes related to low-density lipoprotein (LDL cholesterol derived from a genome-wide association study). We utilized summary-data-based MR (SMR) and inverse-variance-weighted MR (IVWMR) methodologies for estimating effect sizes. Results: SMR analysis indicated that elevated HMGCR expression correlates with increased pulmonary hypertension risk (β=-0.964, se=0.276). Yet, no evident causative link between HMGCR-regulated LDL cholesterol and COVID-19 hospitalization was observed in the IVW-MR analysis (β = -0.21, se= 0.17). Conclusions: Our Mendelian randomization investigation unveiled a possible positive impact of lipid-lowering therapeutics on the prognosis of pulmonary hypertension. Importantly, no causal relation was established between LDL cholesterol and pulmonary hypertension.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.02.23295606v1" target="_blank">Mendelian Randomization Reveals the Role of HMGCR in Pulmonary Arterial Hypertension Treatment, Independent of LDL Cholesterol Concentration</a>
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<li><strong>Modeling spillover dynamics: understanding emerging pathogens of public health concern</strong> -
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The emergence of infectious diseases with pandemic potential is a major public health threat worldwide. According to the World Health Organization, around 60% of the reported emerging infectious diseases are zoonoses and have been triggered by spillover events. Although the dynamics of spillover events are not yet well understood, mathematical modeling has the potential to characterize the highly complex interactions among pathogens, wildlife, humans, and the environment where they coexist. In this work, motivated by discussions on the introductory phase of SARS-CoV-2 towards a pandemic scenario, we address the so far unexplored emergence of novel infectious agents. Aiming at gaining insights into the dynamics of spillover events and the final outcome of an eventual disease outbreak in a population, we propose a continuous time stochastic modeling framework to describe a cross-species disease transmission by coupling the dynamics of animal reservoirs and human hosts. A complete analysis of the system is conducted, followed by numerical experiments where we investigate different scenarios of spillover events. Applied to the emergence of SARS-CoV-2 and monkeypox viruses, our results provide insights into the emergence of new infectious diseases able to cause not only local outbreaks but eventually explosive epidemics towards a pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.02.23296428v1" target="_blank">Modeling spillover dynamics: understanding emerging pathogens of public health concern</a>
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<li><strong>Development of an Integrated Sample Amplification Control for Salivary Point-of-Care Pathogen Testing</strong> -
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Background: The COVID-19 pandemic has led to a rise in point-of-care (POC) and home-based tests, but concerns over usability, accuracy, and effectiveness have arisen. The incorporation of internal amplification controls (IACs), essential control for translational POC diagnostics, could mitigate false- negative and false-positive results due to sample matrix interference or inhibition. Although emerging POC nucleic acid amplification tests (NAATs) for detecting SARS-CoV-2 show impressive analytical sensitivity in the lab, the assessment of clinical accuracy with IACs is often overlooked. In some cases, the IACs were run spatially, complicating assay workflow. Therefore, the multiplex assay for pathogen and IAC is needed. Results: We developed a one-pot duplex reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) assay for saliva samples, a non-invasive and simple collected specimen for POC NAATs. The ORF1ab gene of SARS-CoV-2 was used as a target and a human 18S ribosomal RNA in human saliva was employed as an IAC to ensure clinical reliability of the RT-LAMP assay. The optimized assay could detect SARS-CoV-2 viral particles down to 100 copies/μL of saliva within 30 minutes without RNA extraction. The duplex RT-LAMP for SARS-CoV-2 and IAC is successfully amplified in the same reaction without cross-reactivity. The valid results were easily visualized in triple-line lateral flow immunoassay, in which two lines (flow control and IAC lines) represent valid negative results and three lines (flow control, IAC, and test line) represent valid positive results. This duplex assay demonstrated a clinical sensitivity of 95%, specificity of 100%, and accuracy of 96% in 30 clinical saliva samples. Significance: IACs play a crucial role in ensuring user confidence with respect to the accuracy and reliability of at-home and POC molecular diagnostics. We demonstrated the multiplex capability of SARS-COV-2 and human18S ribosomal RNA RT-LAMP without complicating assay design. This generic platform can be extended in a similar manner to include human18S ribosomal RNA IACs into different clinical sample matrices.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.03.23296477v1" target="_blank">Development of an Integrated Sample Amplification Control for Salivary Point-of-Care Pathogen Testing</a>
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<li><strong>Some principles for using epidemiologic study results to parameterize transmission models</strong> -
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Background: Infectious disease models, including individual based models (IBMs), can be used to inform public health response. For these models to be effective, accurate estimates of key parameters describing the natural history of infection and disease are needed. However, obtaining these parameter estimates from epidemiological studies is not always straightforward. We aim to 1) outline challenges to parameter estimation that arise due to common biases found in epidemiologic studies and 2) describe the conditions under which careful consideration in the design and analysis of the study could allow us to obtain a causal estimate of the parameter of interest. In this discussion we do not focus on issues of generalizability and transportability. Methods: Using examples from the COVID-19 pandemic, we first identify different ways of parameterizing IBMs and describe ideal study designs to estimate these parameters. Given real-world limitations, we describe challenges in parameter estimation due to confounding and conditioning on a post-exposure observation. We then describe ideal study designs that can lead to unbiased parameter estimates. We finally discuss additional challenges in estimating progression probabilities and the consequences of these challenges. Results: Causal estimation can only occur if we are able to accurately measure and control for all confounding variables that create non-causal associations between the exposure and outcome of interest, which is sometimes challenging given the nature of the variables we need to measure. In the absence of perfect control, non-causal parameter estimates should still be used, as sometimes they are the best available information we have. Conclusions: Identifying which estimates from epidemiologic studies correspond to the quantities needed to parameterize disease models, and determining whether these parameters have causal interpretations, can inform future study designs and improve inferences from infectious disease models. Understanding the way in which biases can arise in parameter estimation can inform sensitivity analyses or help with interpretation of results if the magnitude and direction of the bias is understood.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.03.23296455v1" target="_blank">Some principles for using epidemiologic study results to parameterize transmission models</a>
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<li><strong>SARS-CoV-2 neurotropism-induced anxiety and depression-like behaviors require Microglia activation</strong> -
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The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with a wide range of long COVID neurological symptoms. However, the mechanisms governing SARS-CoV-2 neurotropism and its effects on long-term behavioral changes remain poorly understood. Using a highly virulent mouse-adapted SARS-CoV-2 strain, denoted as SARS2-N501YMA30, we demonstrated that intranasal inoculation of SARS2-N501YMA30 results in viral dissemination to multiple brain regions, including the amygdala and hippocampus. Behavioral assays show a significant increase in anxiety- and depression-like behaviors 14 days following viral infection. Moreover, we observed microglia activation following SARS2-N501YMA30 infection, along with an augmentation in microglia-dependent neuronal activity in the amygdala. Pharmacological inhibition of microglial activity subsequent to viral spike inoculation mitigates microglia-dependent neuronal hyperactivity. Furthermore, transcriptomic analysis of infected brains revealed the upregulation of inflammatory and cytokine-related pathways, implicating microglia-driven neuroinflammation in the pathogenesis of neuronal hyperactivity and behavioral abnormality. Overall, these data provide critical insights into the neurological consequences of SARS-CoV-2 infection and underscore microglia as a potential therapeutic target for ameliorating virus-induced neurobehavioral abnormalities.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.02.560570v1" target="_blank">SARS-CoV-2 neurotropism-induced anxiety and depression-like behaviors require Microglia activation</a>
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<li><strong>Virological characteristics correlating with SARS-CoV-2 spike protein fusogenicity</strong> -
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The severe acute respiratory syndrome coronavirus (SARS-CoV-2) spike (S) protein is essential in mediating membrane fusion of the virus with the target cells. Several reports demonstrated that SARS-CoV-2 S protein fusogenicity is reportedly closely associated with the intrinsic pathogenicity of the virus determined using hamster models. However, the association between S protein fusogenicity and other virological parameters remains elusive. In this study, we investigated the virological parameters of eleven previous variants of concern (VOCs) and variants of interest (VOIs) correlating with S protein fusogenicity. S protein fusogenicity was found to be strongly correlated with S1/S2 cleavage efficiency and plaque size formed by clinical isolates. However, S protein fusogenicity was less associated with pseudoviral infectivity, pseudovirus entry efficiency, and viral replication kinetics. Taken together, our results suggest that S1/S2 cleavage efficiency and plaque size could be potential indicators to predict the intrinsic pathogenicity of newly emerged SARS-CoV-2 variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.03.560628v1" target="_blank">Virological characteristics correlating with SARS-CoV-2 spike protein fusogenicity</a>
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<li><strong>A tale of two springs: contrasting forest soundscapes during the COVID-19 lockdown (2020) and after the record snowstorm Filomena (2021) from Central Spain</strong> -
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During the COVID-19 pandemic, humanity temporarily retired from the outdoors. The strict lockdown measures in Spain coincided with the onset of the nesting season of birds, thriving in an unusually quiet environment. Here, we have recorded in forests near San Lorenzo de El Escorial (Central Spain) during the lockdown period in 2020, and the closer to normal spring in 2021. We found strong differences in soundscapes by recording year and location, regardless of the effects of meteorology and human mobility. Species altered their behaviour by increasing their calling intensity during 2021 to cope with higher noise levels, however, acoustic activity was generally less diverse and complex. The difference between years was particularly detrimental for the highest-pitched biophony in 2021. We interpret that an extreme snowfall, Filomena, may have caused a mortality event with lasting effects in the community during the 2021 spring. Since extreme climatic events are likely going to keep happening in the area due to climate change, our data is a useful baseline to guide future conservation efforts, and examine how our activity and climate change are changing the soundscapes of Spanish Mediterranean forests.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.02.560514v1" target="_blank">A tale of two springs: contrasting forest soundscapes during the COVID-19 lockdown (2020) and after the record snowstorm Filomena (2021) from Central Spain</a>
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<li><strong>Implementing evidence ecosystems in the public health service: Development of a seven-step framework for designing tailored training programs</strong> -
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The COVID-19 pandemic has highlighted the importance of local evidence-ecosystems in which academia and practice in the Public Health Service (PHS) are interconnected. However, appropriate organizational structures and well-trained staff are lacking and evidence use in local public health decision-making has to be integrated into training programs in Germany. To address this issue, we developed a toolbox to conceptualize training programs designed to qualify public health professionals for working at the interface between academia and practice. We conducted a scoping review of training programs, key-informant interviews with public health experts, and a multi-professional stakeholder workshop and triangulated their output. The toolbox consists of four core elements, encompassing 15 parameters: (1) content-related aspects, (2) context-related aspects, (3) aspects relevant for determining the training format, and (4) aspects relevant for consolidation and further development. Guiding questions with examples supports the application of the toolbox. The developed seven-step framework aims to facilitate new training programs for knowledge-transfer at the academia-practice interface, equipping public health researchers and practitioners with relevant skills for needs-based PHS research. The joint development of training approaches can foster cross-institutional collaboration and enhance evidence utilization, resulting in long-term resource savings and a stronger evidence base for implementing complex public health measures on site. In this way, co-development of tailored solutions within the local evidence ecosystem has the potential to enhance both scientific and practical impact.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.02.23295684v1" target="_blank">Implementing evidence ecosystems in the public health service: Development of a seven-step framework for designing tailored training programs</a>
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<li><strong>The impact of COVID-19 on medication reviews in English primary care. An OpenSAFELY-TPP analysis of 20 million adult electronic health records.</strong> -
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Background The COVID-19 pandemic caused significant disruption to routine activity in primary care. Medication reviews are an important primary care activity to ensure safety and appropriateness of ongoing prescribing and a disruption could have significant negative implications for patient care. Aim Using routinely collected data, our aim was to i) describe the SNOMED CT codes used to report medication review activity ii) report the impact of COVID-19 on the volume and variation of medication reviews. Design and setting With the approval of NHS England, we conducted a cohort study of 20 million adult patient records in general practice, in-situ using the OpenSAFELY platform. Method For each month between April 2019 - March 2022, we report the percentage of patients with a medication review coded monthly and in the previous 12 months. These measures were broken down by regional, clinical and demographic subgroups and amongst those prescribed high risk medications. Results In April 2019, 32.3% of patients had a medication review coded in the previous 12 months. During the first COVID-19 lockdown, monthly activity substantially decreased (-21.1% April 2020), but the rate of patients with a medication review coded in the previous 12 months was not substantially impacted according to our classification (-10.5% March 2021). There was regional and ethnic variation (March 2022 - London 21.9% vs North West 33.6%; Chinese 16.8% vs British 33.0%). Following the introduction of “structured medication reviews”, the rate of structured medication review in the last 12 months reached 2.9% by March 2022, with higher percentages in high risk groups (March 2022 - care home residents 34.1%, 90+ years 13.1%, high risk medications 10.2%). The most used SNOMED CT medication review code across the study period was Medication review done - 314530002 (59.5%). Conclusion We have reported a substantial reduction in the monthly rate of medication reviews during the pandemic but rates recovered by the end of the study period.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.31.23293419v3" target="_blank">The impact of COVID-19 on medication reviews in English primary care. An OpenSAFELY-TPP analysis of 20 million adult electronic health records.</a>
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<li><strong>Stringent COVID-19 government restrictions were associated with a marked increase in Twitter activity in Europe</strong> -
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The COVID-19 pandemic has had an unprecedented effect on health, well-being, and socioeconomic conditions worldwide. One consequence was changes in social media activity, disruption of schedules, and potentially sleep. We use Twitter data to explore changes in daily and nightly online activity at the onset of the COVID-19 pandemic in 2020. Using a pseudo-random sample of 2,489 users across 6 cities in the UK (Aberdeen, Belfast, Bristol, Cardiff, London, and Manchester), 4 cities in Italy (Milan, Naples, Rome, and Turin), and 4 cities in Sweden (Göteborg, Malmo, Stockholm, Uppsala), we test the extent to which the COVID-19 pandemic changed online activity in Europe. Using a dataset of ~24 million tweets, we show that tweet activity increased by ~20% in 2020 relative to the previous non-pandemic year of 2019. We further show that tweet activity is associated with the degree of government response to COVID-19, particularly during the day, and that the stringency of restrictions was the strongest predictive component of change in tweet count.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/g9apk/" target="_blank">Stringent COVID-19 government restrictions were associated with a marked increase in Twitter activity in Europe</a>
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<li><strong>Lineage frequency time series reveal elevated levels of genetic drift in SARS-CoV-2 transmission in England</strong> -
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Genetic drift in infectious disease transmission results from randomness of transmission and host recovery or death. The strength of genetic drift for SARS-CoV-2 transmission is expected to be high due to high levels of superspreading, and this is expected to substantially impact disease epidemiology and evolution. However, we don’t yet have an understanding of how genetic drift changes over time or across locations. Furthermore, noise that results from data collection can potentially confound estimates of genetic drift. To address this challenge, we develop and validate a method to jointly infer genetic drift and measurement noise from time-series lineage frequency data. Our method is highly scalable to increasingly large genomic datasets, which overcomes a limitation in commonly used phylogenetic methods. We apply this method to over 490,000 SARS-CoV-2 genomic sequences from England collected between March 2020 and December 2021 by the COVID-19 Genomics UK (COG-UK) consortium and separately infer the strength of genetic drift for pre-B.1.177, B.1.177, Alpha, and Delta. We find that even after correcting for measurement noise, the strength of genetic drift is consistently, throughout time, higher than that expected from the observed number of COVID-19 positive individuals in England by 1 to 3 orders of magnitude, which cannot be explained by literature values of superspreading. Our estimates of genetic drift will be informative for parameterizing evolutionary models and studying potential mechanisms for increased drift.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.21.517390v2" target="_blank">Lineage frequency time series reveal elevated levels of genetic drift in SARS-CoV-2 transmission in England</a>
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<li><strong>Protection of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort</strong> -
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<b>Background</b> The protection of fourth dose mRNA vaccination against SARS-CoV-2 is relevant to current global policy decisions regarding ongoing booster roll-out. We estimate the effect of fourth dose vaccination, prior infection, and duration of PCR positivity in a highly-vaccinated and largely prior-COVID-19 infected cohort of UK healthcare workers. <b>Methods</b> Participants underwent fortnightly PCR and regular antibody testing for SARS-CoV-2 and completed symptoms questionnaires. A multi-state model was used to estimate vaccine effectiveness (VE) against infection from a fourth dose compared to a waned third dose, with protection from prior infection and duration of PCR positivity jointly estimated. <b>Results</b> 1,298 infections were detected among 9,560 individuals under active follow-up between September 2022 and March 2023. Compared to a waned third dose, fourth dose VE was 13.1% (95%CI 0.9 to 23.8) overall; 24.0% (95%CI 8.5 to 36.8) in the first two months post-vaccination, reducing to 10.3% (95%CI -11.4 to 27.8) and 1.7% (95%CI -17.0 to 17.4) at 2-4 and 4-6 months, respectively. Relative to an infection >2 years ago and controlling for vaccination, 63.6% (95%CI 46.9 to 75.0) and 29.1% (95%CI 3.8 to 43.1) greater protection against infection was estimated for an infection within the past 0-6, and 6-12 months, respectively. A fourth dose was associated with greater protection against asymptomatic infection than symptomatic infection, whilst prior infection independently provided more protection against symptomatic infection, particularly if the infection had occurred within the previous 6 months. Duration of PCR positivity was significantly lower for asymptomatic compared to symptomatic infection. <b>Conclusions</b> Despite rapid waning of protection, vaccine boosters remain an important tool in responding to the dynamic COVID-19 landscape; boosting population immunity in advance of periods of anticipated pressure, such as surging infection rates or emerging variants of concern. <b>Funding</b> UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, and others.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.29.23296330v2" target="_blank">Protection of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort</a>
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<li><strong>Group A streptococcal cases and treatments during the COVID-19 pandemic and 2022 outbreak: a retrospective cohort study in England using OpenSAFELY-TPP</strong> -
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Objective To investigate the impact of the COVID-19 pandemic on Group A streptococcal (GAS) cases and related antibiotic prescriptions. Design A retrospective cohort study with supporting dashboards with the approval of NHS England. Setting Primary care practices in England using TPP SystmOne software from January 2018 through March 2023. Participants Patients included were those registered at a TPP practice for each month of the study period. Patients with missing sex or age were excluded, resulting in a population of 23,816,470 in January 2018, increasing to 25,541,940 by March 2023. Main outcome measures We calculated monthly counts and crude rates of GAS cases (sore throat/tonsillitis, scarlet fever, invasive group A strep) and prescriptions linked with a GAS case, before (pre-April 2020), during and after (post-April 2021) COVID-19 restrictions. We calculated the maximum and minimum count and rate for each season (years running September-August), and the rate ratio (RR) of the 2022/23 season to the last comparably high season (2017/18). Results Recording of GAS cases and antibiotic prescription linked with a GAS case peaked in December 2022, higher than the 2017/2018 peak. The peak rate of monthly sore throat/tonsillitis (possible group A strep throat) recording was 5.33 per 1,000 (RR 2022/23 versus 2017/18 1.39 (CI: 1.38 to 1.40)). Scarlet fever recording peaked at 0.51 per 1,000 (RR 2.68 (CI: 2.59 to 2.77)), and invasive group A streptococcal infection (iGAS) at 0.01 per 1,000 (RR 4.37 (CI: 2.94 to 6.48)). First line antibiotics with a record of a GAS infection peaked at 2.80 per 1,000 (RR 1.37 (CI:1.35 to 1.38)), alternative antibiotics at 2.03 per 1,000 (RR 2.30 (CI:2.26 to 2.34)), and reserved antibiotics at 0.09 per 1,000 (RR 2.42 (CI:2.24 to 2.61)). For individual antibiotics, azithromycin with GAS indication showed the greatest relative increase (RR 7.37 (CI:6.22 to 8.74)).This followed a sharp drop in recording of cases and associated prescriptions during the period of COVID-19 restrictions where the maximum count and rates were lower than any pre COVID-19 minimum. More detailed demographic breakdowns can be found in our regularly updated dashboard report. Conclusions Rates of scarlet fever, sore throat/tonsillitis and iGAS recording and associated antibiotic prescribing peaked in December 2022. Primary care data can supplement existing infectious disease surveillance through linkages with relevant prescribing data and detailed clinical and demographic subgroups.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.22.23295850v3" target="_blank">Group A streptococcal cases and treatments during the COVID-19 pandemic and 2022 outbreak: a retrospective cohort study in England using OpenSAFELY-TPP</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of Cacao FLAvonoids in LOng Covid Patients (FLALOC)</strong> - <b>Conditions</b>: Long Covid19; Fatigue Syndrome, Chronic <br/><b>Interventions</b>: Dietary Supplement: Flavonoids <br/><b>Sponsors</b>: Guillermo Ceballos Reyes; Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado <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>Exercise Interventions in Post-acute Sequelae of Covid-19</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Exercise <br/><b>Sponsors</b>: University of Virginia <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 Efficacy of the 2023-2024 Updated COVID-19 Vaccines Against COVID-19 Infection</strong> - <b>Conditions</b>: COVID-19; Vaccine-Preventable Diseases; SARS CoV 2 Infection; Upper Respiratory Tract Infection; Upper Respiratory Disease <br/><b>Interventions</b>: Biological: Novavax COVID-19 vaccine (2023-2024 formula XBB containing); Biological: Pfizer COVID-19 mRNA vaccine (2023-2024 formula XBB containing) <br/><b>Sponsors</b>: Sarang K. Yoon, DO, MOH; Westat; Novavax <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>Motivational Interviewing for Vaccine Uptake in Latinx Adults</strong> - <b>Conditions</b>: Vaccine Hesitancy <br/><b>Interventions</b>: Other: EHR alert; Behavioral: Motivational Interviewing; Behavioral: Warm hand off to nurse <br/><b>Sponsors</b>: Boston College; East Boston Neighborhood Health Center; Harvard School of Public Health (HSPH); Boston Children’s Hospital; National Institute of Nursing Research (NINR) <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Trial to Evaluate the Safety of RQ-01 in SARS-CoV-2 Positive Subjects</strong> - <b>Conditions</b>: COVID-19; Infectious Disease; Symptomatic COVID-19 Infection Laboratory-Confirmed; SARS CoV 2 Infection <br/><b>Interventions</b>: Combination Product: RQ-001; Other: Placebo <br/><b>Sponsors</b>: Red Queen Therapeutics, Inc.; PPD <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of “Sputnik Lite” for the Prevention of COVID-19 With Altered Antigenic Composition.</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: “Sputnik Lite” vaccine for the prevention of COVID-19 with altered antigenic composition <br/><b>Sponsors</b>: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study Will Assess the Safety, Neutralizing Activity and Efficacy of AZD3152 in Adults With Conditions Increasing Risk of Inadequate Protective Immune Response After Vaccination and Thus Are at High Risk of Developing Severe COVID-19</strong> - <b>Conditions</b>: COVID-19, SARS-CoV-2 <br/><b>Interventions</b>: Biological: Biological: AZD3152; Biological: Biological: Placebo <br/><b>Sponsors</b>: AstraZeneca <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>Examining the Function of Cs4 on Post-COVID-19 Disorders</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Other: Chinese medicine nutritional supplement Cs4 <br/><b>Sponsors</b>: The University of Hong Kong <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>Stellate Ganglion Block With Lidocaine for the Treatment of COVID-19-Induced Parosmia</strong> - <b>Conditions</b>: Parosmia <br/><b>Interventions</b>: Procedure: Stellate Ganglion Block; Other: Placebo <br/><b>Sponsors</b>: Lawson Health Research Institute <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Amantadine Therapy for Cognitive Impairment in Long COVID</strong> - <b>Conditions</b>: Long COVID; Post-COVID19 Condition; Post-Acute COVID19 Syndrome <br/><b>Interventions</b>: Drug: Amantadine <br/><b>Sponsors</b>: Ohio State 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>CPAP Efficacy in Post-COVID Patients With Sleep Apnea</strong> - <b>Conditions</b>: COVID-19; Sleep Apnea <br/><b>Interventions</b>: Device: Continuous positive airway pressure <br/><b>Sponsors</b>: University of Pittsburgh <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>Cell Therapy With Treg Cells Obtained From Thymic Tissue (thyTreg) to Control the Immune Hyperactivation Associated With COVID-19 (THYTECH2)</strong> - <b>Conditions</b>: Systemic Inflammatory Response Syndrome <br/><b>Interventions</b>: Biological: Allogeneic thyTreg 5.000.000; Biological: Allogeneic thyTreg 10.000.000 <br/><b>Sponsors</b>: Hospital General Universitario Gregorio Marañon; Instituto de Salud Carlos III <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>SA55 Injection: a Potential Therapy for the Prevention and Treatment of COVID-19</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: SA55 Injection; Other: Placebo for SA55 injection <br/><b>Sponsors</b>: Sinovac Life Sciences 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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm G (Metformin)</strong> - <b>Conditions</b>: Covid19 <br/><b>Interventions</b>: Other: Placebo; Drug: Metformin <br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center <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>Mind Body Intervention for Long COVID</strong> - <b>Conditions</b>: Long COVID; Post-Acute Sequelae of COVID-19; COVID Long-Haul <br/><b>Interventions</b>: Behavioral: Mind Body Intervention #1 <br/><b>Sponsors</b>: Beth Israel Deaconess Medical Center <br/><b>Not yet recruiting</b></p></li>
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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>What do we know about the function of SARS-CoV-2 proteins?</strong> - The COVID-19 pandemic has highlighted the importance in the understanding of the biology of SARS-CoV-2. After more than two years since the first report of COVID-19, it remains crucial to continue studying how SARS-CoV-2 proteins interact with the host metabolism to cause COVID-19. In this review, we summarize the findings regarding the functions of the 16 non-structural, 6 accessory and 4 structural SARS-CoV-2 proteins. We place less emphasis on the spike protein, which has been the subject 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>High-affinity binding to the SARS-CoV-2 spike trimer by a nanostructured, trivalent protein-DNA synthetic antibody</strong> - Multivalency enables nanostructures to bind molecular targets with high affinity. Although antibodies can be generated against a wide range of antigens, their shape and size cannot be tuned to match a given target. DNA nanotechnology provides an attractive approach for designing customized multivalent scaffolds due to the addressability and programmability of the nanostructure shape and size. Here, we design a nanoscale synthetic antibody (“nano-synbody”) based on a three-helix bundle DNA…</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>Bioactive metabolites identified from Aspergillus terreus derived from soil</strong> - Aspergillus terreus has been reported to produce many bioactive metabolites that possess potential activities including anti-inflammatory, cytotoxic, and antimicrobial activities. In the present study, we report the isolation and identification of A. terreus from a collected soil sample. The metabolites existing in the microbial ethyl acetate extract were tentatively identified by HPLC/MS and chemically categorized into alkaloids, terpenoids, polyketides, γ-butyrolactones, quinones, 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>Effects of tea, catechins and catechin derivatives on Omicron subvariants of SARS-CoV-2</strong> - The Omicron subvariants of SARS-CoV-2 have multiple mutations in the S-proteins and show high transmissibility. We previously reported that tea catechin (-)-epigallocatechin gallate (EGCG) and its derivatives including theaflavin-3,3’-di-O-digallate (TFDG) strongly inactivated the conventional SARS-CoV-2 by binding to the receptor binding domain (RBD) of the S-protein. Here we show that Omicron subvariants were effectively inactivated by green tea, Matcha, and black tea. EGCG and TFDG strongly…</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>AMPK inhibitor, compound C, inhibits coronavirus replication in vitro</strong> - The coronavirus disease (COVID-19) pandemic has resulted in more than six million deaths by October 2022. Vaccines and antivirals for severe acute respiratory syndrome coronavirus 2 are now available; however, more effective antiviral drugs are required for effective treatment. Here, we report that a potent AMP-activated protein kinase (AMPK) inhibitor, compound C/dorsomorphin, inhibits the replication of the human coronavirus OC43 strain (HCoV-OC43). We examined HCoV-OC43 replication in control…</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 First-In-Human Phase 1 Study of Simnotrelvir, a 3CL-like Protease Inhibitor for Treatment of COVID-19, in Healthy Adult Subjects</strong> - Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.gov Identifier:…</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>An in-vitro evaluation of antifungal, anti-lungcancer (A549), and anti-hyperglycemic activities potential of Andrographis paniculata (Burm. f.) flower extract</strong> - The medical plant research has received more attention among researchers especially after the Covid-19 pandemic. This research performed to evaluate the antifungal, anti-lung cancer (A549), and anti-hyperglycemic activities of aqueous extract of Andrographis paniculata flower. Interestingly, A. paniculata flower aqueous extract contains pharmaceutically valuable phytochemicals such as alkaloid, phenolics, terpenoids, tannins, flavonoids, and protein. It also showed fine antifungal activity…</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>Development in biomarkers of breast cancer: a bibliometric analysis from 2011 to 2020</strong> - CONCLUSIONS: In the past decade, most research has focused on basic and clinical studies, of which microRNAs (miRNAs) and circulating tumor DNAs (ctDNAs) associated with the inhibition and attenuation of BC have become the focus of recent research.</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 loneliness on depression in young people: a multiple mediated effects model</strong> - CONCLUSIONS: The findings indicate that the inability to alleviate negative emotions through socialization and interpersonal companionship during COVID-19 contributed to increased loneliness and subsequent depression. Reduced resilience due to loneliness may lead individuals to project unfavorable interpersonal experiences onto other aspects of life and believe they are incapable of overcoming challenges, thereby deteriorating depression conditions. Enhancing an individual’s resilience may help…</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>Virus on surfaces: Chemical mechanism, influence factors, disinfection strategies, and implications for virus repelling surface design</strong> - While SARS-CoV-2 is generally under control, the question of variants and infections still persists. Fundamental information on how the virus interacts with inanimate surfaces commonly found in our daily life and when in contact with the skin will be helpful in developing strategies to inhibit the spread of the virus. Here in, a critically important review of current understanding of the interaction between virus and surface is summarized from chemistry point-of-view. The…</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 role of cross-reactive immunity to emerging coronaviruses: Implications for novel universal mucosal vaccine design</strong> - Host immune response to coronaviruses and the role of cross-reactivity immunity among different coronaviruses are crucial for understanding and combating the continuing COVID-19 outbreak and potential subsequent pandemics. This review paper explores how previous exposure to common cold coronaviruses and more pathogenic coronaviruses may elicit a protective immune response against SARS-CoV-2 infection, and discusses the challenges posed by some variants of concern that may escape current…</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-structural molecular docking (MOD) combined with molecular dynamics reveal the structural requirements of designing broad-spectrum inhibitors of SARS-CoV-2 entry to host cells</strong> - New variants of SARS-CoV-2 that can escape immune response continue to emerge. Consequently, there is an urgent demand to design small molecule therapeutics inhibiting viral entry to host cells to reduce infectivity rate. Despite numerous in silico and in situ studies, the structural requirement of designing viral-entry inhibitors effective against multiple variants of SARS-CoV-2 has yet to be described. Here we systematically screened the binding of various natural products (NPs) to six…</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>Effect of monovalent COVID-19 vaccines on viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome</strong> - Epstein-Barr virus (EBV) reactivation may be involved in long-COVID symptoms, but reactivation of other viruses as a factor has received less attention. Here we evaluated the reactivation of parvovirus-B19 and several members of the Herpesviridae family (DNA viruses) in patients with long-COVID syndrome. We hypothesized that monovalent COVID-19 vaccines inhibit viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome, thereby reducing clinical symptoms….</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>Antibacterial and anti-corona virus (229E) activity of Nigella sativa oil combined with photodynamic therapy based on methylene blue in wound infection: in vitro and in vivo study</strong> - Microbial skin infections, antibiotic resistance, and poor wound healing are major problems, and new treatments are needed. Our study targeted solving this problem with Nigella sativa (NS) oil and photodynamic therapy based on methylene blue (MB-PDT). Antibacterial activity and minimum inhibitory concentration (MIC) were determined via agar well diffusion assay and broth microdilution, respectively. Transmission electron microscopy (TEM) proved deformations in Staphylococcus aureus ATCC 6538….</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>N-linked glycoproteins and host proteases are involved in swine acute diarrhea syndrome coronavirus entry</strong> - Swine acute diarrhea syndrome coronavirus (SADS-CoV) is highly pathogenic to piglets and poses a major threat to the swine industry. SADS-CoV has a wide cell tropism and pathogenic potential in younger animals. Therefore, understanding how SADS-CoV enters cells is essential for curbing its re-emergence and spread. Here, we report that tunicamycin, an N-linked glycoprotein inhibitor, inhibited the attachment of SADS-CoV to host cells, suggesting that the SADS-CoV receptor may be an N-linked…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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