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190 lines
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<title>25 September, 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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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Basic Psychological Needs, Quality of Motivation, and Protective Behavior Intentions: A Nationally Representative Survey</strong> -
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<div>
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Objective: Citizens’ volitional engagement in protective behaviors is essential for successful pandemic management, as much of the required adherence is beyond authorities’ control and difficult to monitor. Building on the Self-Determination Theory (SDT), this study examines how basic psychological need satisfaction (BPNS) related to COVID-19 behavioral measures is associated with the quality of motivation (autonomous vs. controlled), and whether this quality of motivation is predictive of the intention to wear a face mask and to avoid meeting others. Methods: Cross-sectional survey study involving a nationally representative sample (N = 2272) was conducted in Finland in May 2021, when protective behaviors were recommended to prevent acceleration of the epidemic. Mann-Whitney U tests, Kruskal-Wallis tests, linear regression analysis, and multinomial logistic regression were conducted. Results: All three psychological needs were positively related to autonomous motivation (all p<.001). Satisfaction of autonomy (β = .234) and relatedness (β = .402) had larger effects than competence (β = .091). Autonomous motivation (range Exp(B) = 1.82‒3.55, p = .001) was consistently related to intention to wear a mask and intention to avoid meeting people. Controlled motivation (range Exp(B) = .66‒.93, p = .001‒.457) was associated with decreased protective behavior intentions. The effects of amotivation (range Exp(B) = .65‒1.02, p = .001‒.911) varied across analyses. Conclusions: Fostering autonomous motivation could increase adherence to protective behaviors in situations without clear mandates. The results also suggest that increasing perceptions of pressure or appealing to personal risk and fear may not advance adherence as effectively.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/qgvua/" target="_blank">Basic Psychological Needs, Quality of Motivation, and Protective Behavior Intentions: A Nationally Representative Survey</a>
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</div></li>
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<li><strong>Characterization of Patients Requiring Inpatient Hospital Ethics Consults- A Single Center Study</strong> -
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<div>
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Ethics consultations are often needed at difficult junctures of medical care. However, data on the nature of how patient characteristics, including race/ethnicity, language, and diagnosis, affect ethics consult outcomes are lacking. We performed a retrospective cohort study of all patients who were seen by the Ethics Consult Service between 2017 and 2021 at a large tertiary academic center with the aim of determining whether patient demographic and clinical factors were associated with the timing of ethics consult requests and recommendations of the ethics team. We found that patients admitted for COVID-19 had significantly longer median times to consult from admission compared with other primary diagnoses (19 vs 8 days respectively, p=0.015). Spanish-speaking patients had longer median times to consult from admission compared to English speaking patients (20 vs 7 days respectively, p=0.008), indicating that language barriers may play a role in the timing of ethics consultation. This study demonstrates the need to consider clinical and demographic features when planning and prioritizing ethics consultations at large institutions to enhance consult efficiency, resource utilization, and patient experience and autonomy.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/ce9by/" target="_blank">Characterization of Patients Requiring Inpatient Hospital Ethics Consults- A Single Center Study</a>
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</div></li>
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<li><strong>Mapping the Open-Source Response to Covid-19: Growth, Interactions, and Impact</strong> -
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<div>
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The COVID-19 pandemic necessitated rapid innovation to address emergent healthcare challenges, spotlighting the open-source community’s role in fostering collaborative solutions. This study explores the engagement dynamics within this community by analysing keyword mentions across academic databases, GitHub, and Google search from January 2020 to December 2022. Findings reveal a wave-based engagement pattern with spikes in mentions and search interest during critical pandemic junctures, particularly around ventilators, masks, and personal protective equipment. A challenge in maintaining heightened engagement post the peak of each wave was observed, reflecting the evolving focus of the crisis. The study also noted a shift in focus within the open-source community from ventilators to other healthcare necessities as the pandemic unfolded. These findings underscore the potential of open-source initiatives in fostering agile solutions amidst evolving crisis landscapes. The results advocate for strengthened engagement between policymakers, public health organisations, and the open-source community to align with real-world healthcare needs, augmenting the potential for innovative solutions during future crises. This study illuminates the significance of open-source paradigms as resilient frameworks for navigating complex healthcare challenges and underscores the value of collaborative, transparent, and innovative approaches in addressing global health exigencies.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/wf5c4/" target="_blank">Mapping the Open-Source Response to Covid-19: Growth, Interactions, and Impact</a>
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</div></li>
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<li><strong>Impact of bivalent BA.4/5 BNT162b2 COVID-19 vaccine on acute symptoms, quality of life, work productivity and activity levels among symptomatic US adults testing positive for SARS-CoV-2 at a national retail pharmacy</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: Evidence on the impact of COVID-19 vaccination on symptoms, Health-Related Quality of Life (HRQoL), Work Productivity and Activity Impairment (WPAI) is scarce. We analyzed associations between bivalent BA.4/5 BNT162b2 and these patient-reported outcomes (PROs). Methods: Symptomatic US adults who tested positive for SARS-CoV-2 were recruited between 03/02-05/18/2023. PROs were assessed using a CDC-based symptom questionnaire, EQ-5D-5L, WPAI-GH, and PROMIS Fatigue, from pre-COVID to Week 4 following infection. Multivariable analysis using mixed models for repeated measures was conducted, adjusting for several covariates. Results: The study included 641 participants: 314 vaccinated with bivalent BA.4/5 BNT162b2 and 327 unvaccinated/not up-to-date. Mean (SD) age was 46.5 years (15.9), 71.2% were female, 44.2% reported prior infection, 25.7% had ≥1 comorbidity. The BA.4/5 BNT162b2 cohort reported fewer acute symptoms through Week 4, especially systemic and respiratory symptoms. All PROs were adversely affected, especially at Week 1; however, at that time point, the bivalent BA.4/5 BNT162b2 cohort reported better work performance, driven by less absenteeism, and fewer work hours lost. No significant differences were observed for HRQoL. Conclusions: COVID-19 negatively impacted patient outcomes. Compared with unvaccinated/not up-to-date participants, those vaccinated with bivalent BA.4/5 BNT162b2 reported fewer and less persistent symptoms and improved work performance. Clinicaltrials.gov NCT05160636 Keywords: SARS-CoV-2; BA.4/5 BNT162b2; Bivalent; COVID-19; COVID-19 symptoms; HRQoL; Humanistic; Quality of life; WPAI; PROMIS Fatigue.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.21.23295904v1" target="_blank">Impact of bivalent BA.4/5 BNT162b2 COVID-19 vaccine on acute symptoms, quality of life, work productivity and activity levels among symptomatic US adults testing positive for SARS-CoV-2 at a national retail pharmacy</a>
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</div></li>
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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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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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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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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.22.23295850v1" 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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</div></li>
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<li><strong>Positive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Knockout of the ORF8 protein has repeatedly spread through the global viral population during SARS-CoV-2 evolution. Here we use both regional and global pathogen sequencing to explore the selection pressures underlying its loss. In Washington State, we identified transmission clusters with ORF8 knockout throughout SARS-CoV-2 evolution, not just on novel, high fitness viral backbones. Indeed, ORF8 is truncated more frequently and knockouts circulate for longer than for any other gene. Using a global phylogeny, we find evidence of positive selection to explain this phenomenon: nonsense mutations resulting in shortened protein products occur more frequently and are associated with faster clade growth rates than synonymous mutations in ORF8. Loss of ORF8 is also associated with reduced clinical severity, highlighting the diverse clinical impacts of SARS-CoV-2 evolution.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.21.23295927v1" target="_blank">Positive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution</a>
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</div></li>
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<li><strong>Hierarchical assembly of single-stranded RNA</strong> -
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<div>
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Single-stranded RNA (ssRNA) plays a major role in the flow of genetic information–most notably in the form of messenger RNA (mRNA)–and in the regulation of biological processes. The highly dynamic nature of chains of unpaired nucleobases challenges structural characterizations of ssRNA by experiments or molecular dynamics (MD) simulations alike. Here we use hierarchical chain growth (HCG) to construct ensembles of ssRNA chains. HCG assembles the structures of protein and nucleic acid chains from fragment libraries created by MD simulations. Applied to homo- and heteropolymeric ssRNAs of different lengths, we find that HCG produces structural ensembles that overall are in good agreement with diverse experiments including nuclear magnetic resonance (NMR), small-angle X-ray scattering (SAXS), and single-molecule Forster resonance energy transfer (FRET). The agreement can be further improved by ensemble refinement using Bayesian inference of ensembles (BioEn). HCG can also be used to assemble RNA structures that combine base-paired and unpaired regions, as illustrated for the 5’ untranslated region (UTR) of SARS-CoV-2 mRNA.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.01.551474v2" target="_blank">Hierarchical assembly of single-stranded RNA</a>
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</div></li>
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<li><strong>Liver abnormalities following SARS-CoV-2 infection in children under 10 years of age</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Objective: Beginning in October 2021 in the US and elsewhere, cases of severe pediatric hepatitis of unknown etiology were identified in young children. While the adenovirus and adenovirus-associated virus have emerged as leading etiologic suspects, we attempted to investigate a potential role for SARS-CoV-2 in the development of subsequent liver abnormalities. Design: We conducted a study utilizing retrospective cohorts of de-identified, aggregated data from the electronic health records of over 100 million patients contributed by US health care organizations. Results: Compared to propensity-score-matched children with other respiratory infections, children aged 1-10 years with COVID-19 had a higher risk of elevated transaminases (Hazard ratio (HR) (95% Confidence interval (CI)) 2.16 (1.74-2.69)) or total bilirubin (HR (CI) 3.02 (1.91-4.78)), or new diagnoses of liver diseases (HR (CI) 1.67 (1.21-2.30)) from one to six months after infection. Patients with pre-existing liver abnormalities, liver abnormalities surrounding acute infection, younger age (1-4 years), or illness requiring hospitalization all had similarly elevated risk. Children who developed liver abnormalities following COVID-19 had more pre-existing conditions than those who developed abnormalities following other infections. Conclusion: These results indicate that SARS-CoV-2 may prime the patient for subsequent development of liver infections or non-infectious liver diseases. While rare (~1 in 1,000), SARS-CoV-2 is a risk for subsequent abnormalities in liver function or the diagnosis of diseases of the liver.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.21.23295905v1" target="_blank">Liver abnormalities following SARS-CoV-2 infection in children under 10 years of age</a>
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</div></li>
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<li><strong>Simulation-based validation of a method to detect changes in SARS-CoV-2 reinfection risk</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: Given the high global seroprevalence of SARS-CoV-2, understanding the risk of reinfection becomes increasingly important. Models developed to track trends in reinfection risk should be robust against possible biases arising from imperfect data observation processes. Objectives: We performed simulation-based validation of an existing catalytic model designed to detect changes in the risk of reinfection by SARS-CoV-2. Methods: The catalytic model assumes the risk of reinfection is proportional to observed infections. Validation involved using simulated primary infections, consistent with the number of observed infections in South Africa. We then simulated reinfection datasets that incorporated different processes that may bias inference, including imperfect observation and mortality, to assess the performance of the catalytic model. A Bayesian approach was used to fit the model to simulated data, assuming a negative binomial distribution around the expected number of reinfections, and model projections were compared to the simulated data generated using different magnitudes of change in reinfection risk. We assessed the approach9s ability to accurately detect changes in reinfection risk when included in the simulations, as well as the occurrence of false positives when reinfection risk remained constant. Key Findings: The model parameters converged in most scenarios leading to model outputs aligning with anticipated outcomes. The model successfully detected changes in the risk of reinfection when such a change was introduced to the data. Low observation probabilities (10%) of both primary- and re-infections resulted in low numbers of observed cases from the simulated data and poor convergence. Limitations: The model9s performance was assessed on simulated data representative of the South African SARS-CoV-2 epidemic, reflecting its timing of waves and outbreak magnitude. Model performance under similar scenarios may be different in settings with smaller epidemics (and therefore smaller numbers of reinfections). Conclusions: Ensuring model parameter convergence is essential to avoid false-positive detection of shifts in reinfection risk. While the model is robust in most scenarios of imperfect observation and mortality, further simulation-based validation for regions experiencing smaller outbreaks is recommended. Caution must be exercised in directly extrapolating results across different epidemiological contexts without additional validation efforts.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.21.23295891v1" target="_blank">Simulation-based validation of a method to detect changes in SARS-CoV-2 reinfection risk</a>
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</div></li>
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<li><strong>Anti-SARS-CoV-2 Antibody Levels Associated with COVID-19 Protection in Outpatients Tested for SARS-CoV-2, US Flu VE Network, October 2021 to June 2022</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: We assessed the association between antibody concentration within 5 days of symptom onset and COVID-19 illness among patients enrolled in a test-negative study. Methods: From October 2021 to June 2022, study sites in seven states enrolled and tested respiratory specimens from patients of all ages presenting with acute respiratory illness for SARS-CoV-2 infection using rRT-PCR. In blood specimens, we measured concentration of anti-SARS-CoV-2 antibodies against the ancestral strain spike protein receptor binding domain (RBD) and nucleocapsid (N) antigens in standardized binding antibody units (BAU/mL). Percent reduction in odds of symptomatic COVID-19 by anti-RBD antibody was estimated using logistic regression modeled as (1-adjusted odds ratio of COVID-19)x100, adjusting for COVID-19 vaccination status, age, site, and high-risk exposure. Results: A total of 662 (33%) of 2,018 symptomatic patients tested positive for acute SARS-CoV-2 infection. During the Omicron-predominant period, geometric mean anti-RBD binding antibody concentrations measured 823 BAU/mL (95% CI:690 to 981) among COVID-19 case-patients versus 1,189 BAU/mL (95% CI:1,050 to 1,347) among SARS-CoV-2 test-negative patients. In the adjusted logistic regression, increasing levels of anti-RBD antibodies were associated with reduced odds of COVID-19 for both Delta and Omicron infections. Conclusion: Higher anti-RBD antibodies in patients were associated with protection against symptomatic COVID-19 during emergence of SARS-CoV-2 Delta and Omicron variants.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.21.23295919v1" target="_blank">Anti-SARS-CoV-2 Antibody Levels Associated with COVID-19 Protection in Outpatients Tested for SARS-CoV-2, US Flu VE Network, October 2021 to June 2022</a>
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</div></li>
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<li><strong>Intestinal microbiota programming of alveolar macrophages influences severity of respiratory viral infection</strong> -
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<div>
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Investigating the influence of intestinal microbiota composition on respiratory viral infection (RVI) revealed that segmented filamentous bacteria (SFB), naturally acquired or exogenously administered, protected mice against influenza virus (IAV) infection, as assessed by viral titers, histopathology, and clinical disease features. Such protection, which also applied to RSV and SARS-CoV-2, was independent of interferon and adaptive immunity but required basally resident alveolar macrophages (AM), which, in SFB-negative mice, were quickly depleted as RVI progressed. Examination of AM from SFB-colonized mice revealed that they were intrinsically altered to resist IAV-induced depletion and inflammatory signaling. Yet, AM from SFB-colonized mice were not quiescent. Rather, they directly disabled IAV via enhanced complement production and phagocytosis. Transplant of SFB-transformed AM into SFB-free hosts recapitulated SFB-mediated protection against IAV mechanistically linking intestinal microbiota, AM phenotype, and RVI severity.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.21.558814v1" target="_blank">Intestinal microbiota programming of alveolar macrophages influences severity of respiratory viral infection</a>
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</div></li>
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<li><strong>TMPRSS2 activation of Omicron lineage Spike glycoproteins is regulated by TMPRSS2 cleavage of ACE2</strong> -
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<div>
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Continued high levels spread of SARS-CoV-2 globally enabled accumulation of changes within the Spike glycoprotein, leading to resistance to neutralising antibodies and concomitant changes to entry requirements that increased viral transmission fitness. Herein, we demonstrate a significant change in ACE2 and TMPRSS2 use by primary SARS-CoV-2 isolates that occurred upon arrival of Omicron lineages. Mechanistically we show this shift to be a function of two distinct ACE2 pools based on cleavage or non-cleavage of ACE2 by TMPRSS2 activity. In engineered cells overexpressing ACE2 and TMPRSS2, ACE2 was cleaved by TMPRSS2 and this led to either augmentation or progressive attenuation of pre-Omicron and Omicron lineages, respectfully. In contrast, TMPRSS2 resistant ACE2 restored infectivity across all Omicron lineages through enabling ACE2 binding that facilitated TMPRSS2 spike activation. Therefore, our data support the tropism shift of Omicron lineages to be a function of evolution towards the use of uncleaved pools of ACE2 with the latter consistent with its role as a chaperone for many tissue specific amino acid transport proteins.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.22.558930v1" target="_blank">TMPRSS2 activation of Omicron lineage Spike glycoproteins is regulated by TMPRSS2 cleavage of ACE2</a>
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</div></li>
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<li><strong>Healthcare system barriers impacting the care of Canadians with myalgic encephalomyelitis: a scoping review</strong> -
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Background: Myalgic encephalomyelitis (ME, also known as chronic fatigue syndrome or ME/CFS) is a debilitating, complex, multi-system illness. Developing a comprehensive understanding of the multiple and interconnected barriers to optimal care will help advance strategies and care models to improve quality of life for people living with ME in Canada. Objectives: To: (1) identify and systematically map the available evidence; (2) investigate the design and conduct of research; (3) identify and categorize key characteristics; and (4) identify and analyze knowledge gaps related to healthcare system barriers for people living with ME in Canada. Methods: The protocol was preregistered in July 2022. Peer-reviewed and grey literature was searched, and patient partners retrieved additional records. Eligible records were Canadian, included people with ME/CFS and included data or synthesis relevant to healthcare system barriers. Results: In total, 1821 records were identified, 406 were reviewed in full, and 21 were included. Healthcare system barriers arose from an underlying lack of consensus and research on ME and ME care; the impact of long-standing stigma, disbelief, and sexism; inadequate or inconsistent healthcare provider education and training on ME; and the heterogeneity of care coordinated by family physicians. Conclusions: People living with ME in Canada face significant barriers to care, though this has received relatively limited attention. This synthesis, which points to several areas for future research, can be used as a starting point for researchers, healthcare providers and decision-makers who are new to the area or encountering ME more frequently due to the COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.20.23295809v2" target="_blank">Healthcare system barriers impacting the care of Canadians with myalgic encephalomyelitis: a scoping review</a>
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<li><strong>Spatio-temporal surveillance and early detection of SARS-CoV-2 variants of concern: a retrospective analysis</strong> -
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The SARS-CoV-2 pandemic has been characterized by the repeated emergence of genetically distinct virus variants of increased transmissibility and immune evasion compared to pre-existing lineages. In many countries, their containment required the intervention of public health authorities and the imposition of control measures. While the primary role of testing is to identify infection, target treatment, and limit spread (through isolation and contact tracing), a secondary benefit is in terms of surveillance and the early detection of new variants. Here we study the spatial invasion and early spread of the Alpha, Delta, and Omicron (BA.1 and BA.2) variants in England from September 2020 to February 2022 using the random neighbourhood covering (RaNCover) method. This is a statistical technique for the detection of aberrations in spatial point processes, which we tailored here to community PCR (polymerase-chain-reaction) test data where the TaqPath kit provides a proxy measure of the switch between variants. Retrospectively, RaNCover detected the earliest signals associated with the four novel variants that led to large infection waves in England. With suitable data our method therefore has the potential to rapidly detect outbreaks of future SARS-CoV-2 variants, thus helping to inform targeted public health interventions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.06.23292295v2" target="_blank">Spatio-temporal surveillance and early detection of SARS-CoV-2 variants of concern: a retrospective analysis</a>
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</div></li>
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<li><strong>Human origin ascertained for SARS-CoV-2 Omicron-like spike sequences detected in wastewater: a targeted surveillance study of a cryptic lineage in an urban sewershed</strong> -
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Summary Background: The origin of novel SARS-CoV-2 spike sequences found in wastewater, without corresponding detection in clinical specimens, remains unclear. We sought to determine the origin of one such “cryptic” wastewater lineage by tracking and characterizing its persistence and genomic evolution over time. Methods: We first detected a cryptic lineage in Wisconsin municipal wastewater in January 2022. By systematically sampling wastewater from targeted sub-sewershed lines and maintenance holes using compositing autosamplers, we traced this lineage (labeled WI-CL-001) to its source at a single commercial building. There we detected WI-CL-001 at concentrations as high as 2.7 x 109 genome copies per liter (gc/L) via RT-dPCR. In addition to using metagenomic 12s rRNA sequencing to determine the virus9s host species, we also sequenced SARS-CoV-2 spike receptor binding domains (RBDs), and where possible, whole viral genomes to identify and characterize the evolution of this lineage over the 13 consecutive months that it was detectable. Findings: The vast majority of 12s rRNAs sequenced from wastewater leaving the identified source building were human. Additionally, we generated over 100 viral RBD and whole genome sequences from wastewater samples containing the cryptic lineage collected between January 2022 and January 2023. These sequences contained a combination of fixed nucleotide substitutions characteristic of Pango lineage B.1.234, which circulated in humans in Wisconsin at low levels from October 2020 to February 2021. Despite this, mutations in the spike gene, and elsewhere, resembled those subsequently found in Omicron variants. Interpretation: We propose that prolonged detection of WI-CL-001 in wastewater represents persistent shedding of SARS-CoV-2 from a single human initially infected by an ancestral B.1.234 virus. The accumulation of convergent “Omicron-like” mutations in WI-CL-0019s ancestral B.1.234 genome likely reflects persistent infection and extensive within-host evolution. Funding: The Rockefeller Foundation, Wisconsin Department of Health Services, Centers for Disease Control and Prevention (CDC), National Institute on Drug Abuse (NIDA), and the Center for Research on Influenza Pathogenesis and Transmission. Research in context Evidence before this study: To identify other studies that characterized unusual wastewater-specific SARS-CoV-2 lineages, we conducted a PubMed search using the keywords “cryptic SARS-CoV-2 lineages” or “novel SARS-CoV-2 lineages” in addition to “wastewater” on May 9, 2023. From the 18 papers retrieved, only two reported wastewater-specific cryptic lineages. These lineages were identified by members of our author team in wastewater from California, Missouri, and New York City. None of these could be definitively traced to a specific source. A third study in Nevada identified a unique recombinant variant (designated Pango lineage XL) in wastewater, which was also discovered in two clinical specimens from the same community. However, it was unclear whether the clinical specimens collected were from the same individual(s) responsible for the virus detected in the wastewater. To our knowledge, no prior study has successfully traced novel SARS-CoV-2 lineages detected in wastewater back to a specific location. How and where cryptic lineages are introduced into wastewater is not known. The added value of this study: This study documents the presence and likely source of a novel and highly divergent cryptic SARS-CoV-2 lineage detected in Wisconsin wastewater for 13 months. In contrast to previously reported cryptic lineages, we successfully traced the lineage (WI-CL-001) to a single commercial building with approximately 30 employees. The exceptionally high viral RNA concentrations at the source building facilitated the tracing effort and allowed for the sequencing of WI-CL-0019s whole genome, expanding our view of the lineage9s mutational landscape beyond the spike gene. Implications of all the available evidence: WI-CL-0019s persistence in wastewater, its heavily mutated Omicron-like genotype, and its identified point source at a human-occupied commercial building all support the hypothesis that cryptic wastewater lineages can arise from persistently infected humans. Because cryptic wastewater lineages have some amino acid changes that subsequently emerge in circulating viruses, increased global monitoring of such lineages could help forecast variants that may arise in the future.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.28.22281553v5" target="_blank">Human origin ascertained for SARS-CoV-2 Omicron-like spike sequences detected in wastewater: a targeted surveillance study of a cryptic lineage in an urban sewershed</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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm G (Metformin)</strong> - <b>Condition</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>SA55 Injection: a Potential Therapy for the Prevention and Treatment of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SA55 Injection; Other: Placebo for SA55 injection<br/><b>Sponsor</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>A Study to Assess the Safety, Tolerability and Preliminary Efficacy of HH-120 for the Treatment of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: HH-120; Drug: placebo<br/><b>Sponsor</b>: Huahui Health<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>Psychosomatic, Physical Activity or Both for Post-covid19 Syndrom</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Behavioral: Exercise Therapy; Behavioral: Psychotherapy<br/><b>Sponsors</b>: Hannover Medical School; Health Insurance Audi BKK; occupational health service Volkswagen AG; Helmholtz Centre for Infection Research<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 Investigate the Prevention of COVID-19 withVYD222 in Adults With Immune Compromise and in Participants Aged 12 Years or Older Who Are at Risk of Exposure to SARS-CoV-2</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2<br/><b>Interventions</b>: Drug: VYD222; Drug: Normal saline<br/><b>Sponsor</b>: Invivyd, Inc.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Omicron BA.4/5-Delta COVID-19 Vaccine Phase I Clinical Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Omicron BA.4/5-Delta strain recombinant novel coronavirus protein vaccine (CHO cells); Biological: Placebo<br/><b>Sponsors</b>: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention<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>Reducing COVID-19 Vaccine Hesitancy Among Hispanic Parents</strong> - <b>Conditions</b>: Vaccine-Preventable Diseases; COVID-19 Pandemic; Health-Related Behavior; Health Knowledge, Attitudes, Practice; Narration<br/><b>Interventions</b>: Behavioral: Baseline surveys; Behavioral: Digital Storytelling Intervention; Behavioral: Information Control Intervention<br/><b>Sponsors</b>: Arizona State University; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)<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-pharmacological and TCM-based Treatment for Long COVID Symptoms</strong> - <b>Condition</b>: Long Covid19<br/><b>Intervention</b>: Behavioral: Acupuncture and TCM-based lifestyle management<br/><b>Sponsor</b>: The Hong Kong Polytechnic 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>Evaluation of Safety and Immunogenicity of a SARS-CoV-2(Severe Acute Respiratory Syndrome Coronavirus 2) Booster Vaccine (LEM-mR203)</strong> - <b>Conditions</b>: COVID-19 Infection; COVID-19 Vaccine Adverse Reaction<br/><b>Interventions</b>: Biological: LEM-mR203; Biological: Placebo<br/><b>Sponsor</b>: Lemonex<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>Condition</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 Novel Coronavirus Broad-spectrum Neutralizing Antibody Nasal Spray in Health People</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: SA55 nasal spray<br/><b>Sponsor</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>A Bioequivalence Trial of Fasting Single Oral STI-1558 Capsule in Healthy Chinese Subjects</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: STI-1558<br/><b>Sponsor</b>: Zhejiang ACEA Pharmaceutical Co. Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Determine the Tolerability of Intranasal LMN-301</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: LMN-301<br/><b>Sponsor</b>: Lumen Bioscience, Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mind Body Intervention for Long COVID</strong> - <b>Conditions</b>: Long COVID; Post-Acute Sequelae of COVID-19; COVID Long-Haul<br/><b>Intervention</b>: Behavioral: Mind Body Intervention #1<br/><b>Sponsor</b>: Beth Israel Deaconess Medical Center<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 of Simultaneous mRNA COVID-19 Vaccine With Other Childhood Vaccines in Young Children</strong> - <b>Conditions</b>: Fever After Vaccination; Fever; Seizures Fever<br/><b>Interventions</b>: Biological: Pfizer-BioNTech COVID-19 Vaccine; Biological: Routine Childhood Vaccinations<br/><b>Sponsors</b>: Duke University; Kaiser Permanente; Columbia University; Children’s Hospital Medical Center, Cincinnati; Centers for Disease Control and Prevention<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Heat shock protein 90 inhibition in the endothelium</strong> - No abstract</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>Determinants of <em>de novo</em> B cell responses to drifted epitopes in post-vaccination SARS-CoV-2 infections</strong> - Vaccine-induced immunity may impact subsequent de novo responses to drifted epitopes in SARS-CoV-2 variants, but this has been difficult to quantify due to the challenges in recruiting unvaccinated control groups whose first exposure to SARS-CoV-2 is a primary infection. Through local, statewide, and national SARS-CoV-2 testing programs, we were able to recruit cohorts of individuals who had recovered from either primary or post-vaccination infections by either the Delta or Omicron BA.1…</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>Recurrent Viral Capture of Cellular Phosphodiesterases that Antagonize OAS-RNase L</strong> - Phosphodiesterases (PDEs) encoded by viruses are putatively acquired by horizontal transfer of cellular PDE ancestor genes. Viral PDEs inhibit the OAS-RNase L antiviral pathway, a key effector component of the innate immune response. Although the function of these proteins is well-characterized, the origins of these gene acquisitions is less clear. Phylogenetic analysis revealed at least five independent PDE acquisition events by ancestral viruses. We found evidence that PDE-encoding genes were…</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>Complete substitution with modified nucleotides suppresses the early interferon response and increases the potency of self-amplifying RNA</strong> - Self-amplifying RNA (saRNA) will revolutionize vaccines and in situ therapeutics by enabling protein expression for longer duration at lower doses. However, a major barrier to saRNA efficacy is the potent early interferon response triggered upon cellular entry, resulting in saRNA degradation and translational inhibition. Substitution of mRNA with modified nucleotides (modNTPs), such as N1-methylpseudouridine (N1mΨ), reduce the interferon response and enhance expression levels. Multiple attempts…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Regulation of human interferon signaling by transposon exonization</strong> - Innate immune signaling is essential for clearing pathogens and damaged cells, and must be tightly regulated to avoid excessive inflammation or autoimmunity. Here, we found that the alternative splicing of exons derived from transposable elements is a key mechanism controlling immune signaling in human cells. By analyzing long-read transcriptome datasets, we identified numerous transposon exonization events predicted to generate functional protein variants of immune genes, including the type I…</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>Modelling and analysis of the complement system signalling pathways: roles of C3, C5a and pro-inflammatory cytokines in SARS-CoV-2 infection</strong> - The complement system is an essential part of innate immunity. It is activated by invading pathogens causing inflammation, opsonization, and lysis via complement anaphylatoxins, complement opsonin’s and membrane attack complex (MAC), respectively. However, in SARS-CoV-2 infection overactivation of complement system is causing cytokine storm leading to multiple organs damage. In this study, the René Thomas kinetic logic approach was used for the development of biological regulatory network (BRN)…</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>Utility of coproporphyrin-I determination in first-in-human study for early evaluation of OATP1B inhibitory potential based on investigation of ensitrelvir, an oral SARS-CoV-2 3C-like protease inhibitor</strong> - Coproporphyrin-I (CP-I) has been investigated as an endogenous biomarker of organic anion transporting polypeptide (OATP) 1B. Here, we determined the CP-I concentrations in a cocktail drug-drug interaction (DDI) study of ensitrelvir to evaluate the OATP1B inhibitory potential because ensitrelvir had increased plasma concentrations of rosuvastatin in this study, raising concerns about breast cancer resistance protein and OATP1B inhibition. Furthermore, CP-I concentrations were compared between…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Protection of eIF2B from inhibitory phosphorylated eIF2: a viral strategy to maintain mRNA translation during the PKR-triggered integrated stress response</strong> - The integrated stress response (ISR) protects cells from a variety of insults. Once elicited (e.g. by virus infections), it eventually leads to the block of mRNA translation. Central to the ISR are the interactions between translation initiation factors eIF2 and eIF2B. Under normal conditions, eIF2 drives the initiation of protein synthesis through hydrolysis of GTP, which becomes replenished when binding to the guanine nucleotide exchange factor (GEF) eIF2B. The antiviral branch of the ISR is…</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>Computational analysis of substrate recognition of Sars-Cov-2 Mpro main protease</strong> - M^(pro) main protease takes an essential role in the Sars-Cov-2 viral life cycle by releasing the individual protein from the single poly-peptide chain via proteolytic cleavage in the beginning of the viral infection. Interfering with this step by inhibiting the protease with small compound-based inhibitors has been proven to be an effective strategy to treat the infection. Thus, understanding the substrate recognition mechanism of the M^(pro) main protease has gained great interest from 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>Green synthesis, characterization, anti-SARS-CoV-2 entry, and replication of lactoferrin-coated zinc nanoparticles with halting lung fibrosis induced in adult male albino rats</strong> - The ethanolic extract of Coleus forskohlii Briq leaves was employed in the green synthesis of zinc nanoparticles (Zn-NPs) by an immediate, one-step, and cost-effective method in the present study. Zn-NPs were coated with purified bovine lactoferrin (LF) and characterized through different instrumental analysis. The biosynthesized Zn-NPs were white in color revealing oval to spherical-shaped particles with an average size of 77 ± 5.50 nm, whereas LF-coated Zn-NPs (LF-Zn-NPs) revealed a larger…</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>Age and prior vaccination determine the antibody level in children with primary SARS-CoV-2 Omicron infection</strong> - CONCLUSIONS: In our study, children aged 6 months to 2 years have the highest antibody responses to SARS-CoV-2 Omicron variant infection. Age and prior vaccination are the main factors influencing the immunogenicity of SARS-CoV-2 infection.</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 Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the Novavax COVID-19 Vaccine (NVX-CoV2373), a recombinant spike protein vaccine with Matrix-M adjuvant to prevent disease caused by SARS-CoV-2 viruses</strong> - Novavax, a global vaccine company, began evaluating NVX-CoV2373 in human studies in May 2020 and the pivotal placebo-controlled phase 3 studies started in November 2020; five clinical studies provided adult and adolescent clinical data for over 31,000 participants who were administered NVX-CoV2373. This extensive data has demonstrated a well-tolerated response to NVX-CoV2373 and high vaccine efficacy against mild, moderate, or severe COVID-19 using a two-dose series (Dunkle et al., 2022) [1],…</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 SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes several proteins that inhibit host interferon responses. Among these, ORF6 antagonizes interferon signaling by disrupting nucleocytoplasmic trafficking through interactions with the nuclear pore complex components Nup98-Rae1. However, the roles and contributions of ORF6 during physiological infection remain unexplored. We assessed the role of ORF6 during infection using recombinant viruses carrying a deletion or…</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>TGF-β1 reduces the differentiation of porcine IgA-producing plasma cells by inducing IgM<sup>+</sup> B cells apoptosis via Bax/Bcl2-Caspase3 pathway</strong> - Transforming growth factor β1 (TGF-β1) performs a critical role in maintaining homeostasis of intestinal mucosa regulation and controls the survival, proliferation, and differentiation of many immune cells. In this study, we discovered that the infection of porcine epidemic diarrhea virus (PEDV), a coronavirus, upregulated TGF-β1 expression via activating Tregs. Besides, recombinant porcine TGF-β1 decreased the percentage of CD21^(+) B cells within the lymphocyte population in vitro. We further…</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>Therapeutic benefits of prophetic medicine remedies in treating hematological diseases (A review article)</strong> - Hematological disorders are common medical ailments constituting an important cause of morbidity and mortality worldwide, which may be managed efficiently using different prophetic medicine remedies as adjuvants to current therapeutics. Prophetic medicine includes the body of knowledge about medicine that has been derived from the deeds, customs (sunnah), ahadith (sayings), actions, and agreements of Prophet Muhammad, peace be upon him. This review article aims at exploring the magnitude of…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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