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194 lines
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<title>02 May, 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>Correcting prevalence estimation for biased sampling with testing errors</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Sampling for prevalence estimation of infection is subject to bias by both oversampling of symptomatic individuals and error-prone tests. This results in naive estimators of prevalence (i.e., proportion of observed infected individuals in the sample) that can be very far from the true proportion of infected. In this work, we present a method of prevalence estimation that reduces both the effect of bias due to testing errors and oversampling of symptomatic individuals, eliminating it altogether in some scenarios. Moreover, this procedure considers stratified errors in which tests have different error rate profiles for symptomatic and asymptomatic individuals. This results in easily implementable algorithms, for which code is provided, that produce better prevalence estimates than other methods (in terms of reducing and/or removing bias), as demonstrated by formal results, simulations, and on COVID-19 data from the Israeli Ministry of Health.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.11.12.21266254v3" target="_blank">Correcting prevalence estimation for biased sampling with testing errors</a>
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</div></li>
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<li><strong>New Approach to the SIR Inversion Problem: From the 1905-1906 Plague Outbreak in the Isle of Bombay to the 2021-2022 Omicron Surge in New York City</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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We describe a novel approach to recovering the underlying parameters of the SIR dynamic epidemic model from observed data on case incidence or deaths. We formulate a discrete-time approximation to the original continuous-time model and search for the parameter vector that minimizes the standard least squares criterion function. We show that the gradient vector and matrix of second-order derivatives of the criterion function with respect to the parameters adhere to their own systems of difference equations and thus can be exactly calculated iteratively. Applying our new approach, we estimate four-parameter SIR models on two datasets: (1) daily reported cases of COVID-19 during the SARS-CoV-2 Omicron/BA.1 surge of December 2021 - March 2022 in New York City; and (2) weekly deaths from a plague outbreak on the Isle of Bombay during December 1905 - July 1906, originally studied by Kermack and McKendrick in their now-classic 1927 paper. The estimated parameters from the COVID-19 data suggest a duration of persistent infectivity beyond that reported in small-scale clinical studies of mostly symptomatic subjects. The estimated parameters from the plague data suggest that the Bombay outbreak was in fact driven by pneumonic rather than bubonic plague.
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</p>
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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/10.1101/2023.03.13.23287177v2" target="_blank">New Approach to the SIR Inversion Problem: From the 1905-1906 Plague Outbreak in the Isle of Bombay to the 2021-2022 Omicron Surge in New York City</a>
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</div></li>
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<li><strong>Elevated Levels of IL-6 in IgA Nephropathy patients are induced by an Epigenetically Driven Mechanism Triggered by Viral and Bacterial RNA</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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Immunoglobulin A nephropathy (IgAN) is the most frequent primary glomerulonephritis characterized by the presence of IgA immune complexes in the glomeruli. Recently, a multihit model has been proposed to describe the pathogenesis of IgAN, but it is believed that further predisposing factors are present, including immunological, genetic and environmental factors. Newly, the role of IL-6 in pathogenesis is becoming increasingly important but reason why levels of IL-6 are elevated in IgAN patients is not well understood. One attainable hypothesis on high levels of IL-6 in IgAN comes out from our recent whole genome DNA methylation screening in IgAN patients, that identified, among others, a hypermethylated region comprising Vault RNA 2-1 (VTRNA2-1), a non-coding RNA. Here we confirm that VTRNA2-1 is low expressed in IgAN subjects compared to HS and we found that also in transplanted IgAN patients (TP-IgAN), compared to non-IgAN transplanted patients (TP), the VTRNA2-1 transcript was expressed at level very low. We found that in IgAN patients with downregulated VTRNA2-1, PKR is overactivated, coherently with the role of the VTRNA2-1 that binds to PKR and inhibits its phosphorylation. The loss of the VTRNA2-1 natural restrain caused the activation of CREB by PKR, a classical cAMP-inducible CRE-binding factor interacting with a region of the IL-6 promoter and leading to IL-6 production, both in IgAN and in TP-IgAN patients. PKR is normally activated by bacterial and viral RNA and we found that both the RNA poly(I:C), the and the COVID-19 RNA-vaccine stimulation significantly increase the IL-6 levels in PBMCs from HS but had an opposite effect in those from IgAN patients. In conclusion, the discovery of the upregulated VTRNA2-1/PKR/CREB/IL-6 pathway in IgAN patients may provide novel approach to treat the disease and may be useful for development of precision nephrology and personalized therapy, possibly by checking the VTRNA2-1 methylation level in IgAN patients.
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</p>
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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/10.1101/2022.03.05.22271944v3" target="_blank">Elevated Levels of IL-6 in IgA Nephropathy patients are induced by an Epigenetically Driven Mechanism Triggered by Viral and Bacterial RNA</a>
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</div></li>
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<li><strong>Evaluation of the Pilot Wastewater Surveillance for SARS-CoV-2 in Norway, June 2022 - March 2023</strong> -
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Background: During the COVID-19 pandemic, wastewater-based surveillance gained great international interest as an additional tool to monitor SARS-CoV-2. In autumn 2021, the Norwegian Institute of Public Health decided to pilot a national wastewater surveillance (WS) system for SARS-CoV-2 and its variants between June 2022 and March 2023. We evaluated the system to assess if it met its objectives and its attribute-based performance. Methods: We adapted the available guidelines for evaluation of surveillance systems. The evaluation was carried out as a descriptive analysis and consisted of the following three steps: (i) description of the WS system, (ii) identification of users and stakeholders, and (iii) analysis of the system attributes and performance including sensitivity, specificity, timeliness, usefulness, representativeness, simplicity, flexibility, stability, and communication. Cross-correlation analysis was performed to assess the system ability to provide early warning signal of new wave of infections. Results: The pilot WS system was a national surveillance system using existing wastewater infrastructures from the largest Norwegian municipalities. We found that the system was sensitive, timely, useful, representative, simple, flexible, acceptable, and stable to follow the general trend of infection. Preliminary results indicate that the system could provide an early signal of changes in variant distribution. However, challenges may arise with: (i) specificity due to temporary fluctuations of RNA levels in wastewater, (ii) representativeness when downscaling, and (iii) flexibility and acceptability when upscaling the system due to limited resources and/or capacity. Conclusions: Our results showed that the pilot WS system met most of its surveillance objectives. The system was able to provide an early warning signal of 1-2 weeks, and the system was useful to monitor infections at population level and complement routine surveillance when individual testing activity was low. However, temporary fluctuations of WS values need to be carefully interpreted. To improve quality and efficiency, we recommend to standardise and validate methods for assessing trends of new waves of infection and variants, evaluate the WS system using a longer operational period particularly for new variants, and conduct prevalence studies in the population to calibrate the system and improve data interpretation.
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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/10.1101/2023.04.27.23289199v2" target="_blank">Evaluation of the Pilot Wastewater Surveillance for SARS-CoV-2 in Norway, June 2022 - March 2023</a>
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</div></li>
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<li><strong>Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design</strong> -
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Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or “Long COVID”) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH’s REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of five cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n=10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. Conclusions and Relevance: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions.
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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/10.1101/2023.04.27.23289228v1" target="_blank">Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design</a>
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</div></li>
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<li><strong>Lack of detection of SARS-CoV-2 in British wildlife 2020-21 and first description of a stoat (Mustela erminea) Minacovirus</strong> -
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<div>
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Repeat spill over of SARS-CoV-2 into new hosts has highlighted the critical role of cross species transmission of coronaviruses and establishment of new reservoirs of virus in pandemic and epizootic spread of coronaviruses. Species particularly susceptible to SARS-CoV-2 spill-over include Mustelidae (mink, ferrets and related animals) and cricetid rodents (hamsters and related animals). These predispositions led us to screen British wildlife with sarbecovirus specific qPCR and pan coronavirus PCR assays for SARS-CoV-2 using samples collected during the human pandemic to establish if widespread spill-over was occurring. Fourteen wildlife species (n=402) were tested, including : 2 Red Foxes (Vulpes vulpes), 101 Badgers (Meles meles), 2 wild American Mink (Neovison vison), 41 Pine Marten (Martes martes), 2 Weasels (Mustela nivalis), 7 Stoats (Mustela erminea), 108 Water Voles (Arvicola amphibius), 39 Bank voles (Myodes glareolous), 10 Field Voles ( Microtus agrestis), 15 Wood Mice (Apodemus sylvaticus), 1 Common Shrew (Sorex aranaeus), 2 Pygmy Shrews (Sorex minutus), 2 Hedgehogs (Erinaceus europaeus) and 75 Eurasian Otters (Lutra lutra). No cases of SARS-CoV-2 were detected in any animals, however a novel minacovirus related to mink and ferret alphacoronaviruses was detected in stoats recently introduced to the Orkney Islands. This group of viruses is of interest due to pathogenicity in ferrets. The impact of this virus on the health of stoat populations remains to be established.
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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/10.1101/2023.04.28.538769v1" target="_blank">Lack of detection of SARS-CoV-2 in British wildlife 2020-21 and first description of a stoat (Mustela erminea) Minacovirus</a>
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<li><strong>Characterising subgroups of people with severe COVID anxiety by latent profile analysis.</strong> -
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Background: Severe COVID anxiety describes people whose experiences of the COVID-19 pandemic are overwhelming, and have lead to patterns of behaviours that add little protective benefit but are at the expense of other priorities in life. It appears to be a complex social and psychological phenomenon, influenced by demographic and social factors. Identifying subgroups of people with severe COVID anxiety would better place clinicians to assess and support this distress where indicated. Methods: Measurement tools assessing depression, generalised and health anxiety, obsessive-compulsive symptoms, personality difficulty and alcohol use from 284 people living in United Kingdom with severe COVID anxiety were explored with latent profile analysis. Further analyses examined the associations of identified clusters with demographic and social factors and daily functioning, quality of life and protective behaviours. Results: A model with 4 classes provided the best fit. Distinct patterns of psychopathology emerged which were variably associated with demographic factors and COVID behaviours. Limitations: Given the complex aetiology of COVID anxiety a number of factors which might better cluster subgroups are likely to have gone uncollected. Moreover, using data collected at a single time-point limits these results ability to conclude whether observed relationships were the product of the pandemic or longstanding. Conclusions: People living with severe COVID anxiety are a heterogenous group. This analysis adds to evidence that certain health behaviours and demographic factors are inextricably linked to poor mental health in people with COVID anxiety, and that targeting health behaviours with specific intervention might be beneficial.
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</p>
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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/10.1101/2023.04.28.23289248v1" target="_blank">Characterising subgroups of people with severe COVID anxiety by latent profile analysis.</a>
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<li><strong>Effect of vaccination on time till Long COVID, a comparison of two ways to model effect of vaccination and two outcome definitions</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Long COVID, or post-COVID syndrome, is a constellation of symptoms observed in patients at least four weeks after COVID-19 infection. We analyzed the effect of COVID-19 vaccination status on risk of either developing Long COVID symptoms or being diagnosed with Long COVID. In separate analyses we compared the effect of vaccination status at time of COVID-19 infection and the effect of vaccination status as a time-dependent covariate where vaccination could occur at any point with respect to COVID-19 infection. To address this question, we identified a subset of adult patients from Truveta Data who experienced a COVID-19 infection as indicated by a positive laboratory test between 2021-10-01 and 2022-11-31. We considered two distinct ways of modeling the effect of vaccination status (time-independent and time-dependent) and two distinct outcomes of interest (Long COVID symptoms or diagnosis with Long COVID), representing four distinct analyses. The presence of Long COVID symptoms was defined as the presence of one or more new symptoms consistent with COVID-19/Long COVID at least four weeks post COVID-19 infection. Diagnosis of Long COVID was determined by the presence of one or more ICD-10-CM or SNOMED-CT codes explicitly identifying a patient as having been diagnosed with Long COVID. Our analysis focusing on the effect of COVID-19 vaccination status at time of COVID-19 infection found that patients who had completed a primary COVID-19 vaccination sequence or had completed a primary vaccination sequence and received a booster dose at time of COVID-19 infection were on average at lower risk of either developing Long COVID symptoms or being diagnosed with Long COVID than unvaccinated patients (vaccinated versus unvaccinated HR of symptoms 0.9 [0.87-0.94], HR of diagnosis 0.86 [0.74-0.99]; vaccinated and boosted versus unvaccinated HR of symptoms 0.87 [0.83-0.91], HR of diagnosis 0.81 [0.69-0.95]). We do not find evidence that having received a booster dose in addition to having completed a primary vaccination sequence offers additional protection over having completed the primary sequence alone (vaccinated and boosted versus vaccinated HR of symptoms 0.96 [0.91-1.01], HR of diagnosis 0.94-1.13) . Our analysis of COVID-19 vaccination status modeled as a time-dependent covariate yielded similar results for patients who had completed a primary COVID-19 vaccination sequence or had completed a primary vaccination sequence and a booster dose. Both groups were on average at lower risk of developing Long COVID symptoms or being diagnosed with Long COVID than patients who where never vaccinated (vaccinated versus unvaccinated HR of symptoms 0.91 [0.88-0.95], HR of diagnosis 0.86 [0.75-0.99]; vaccinated and boosted versus unvaccinated HR of symptoms 0.88 [0.85-0.91], HR of diagnosis 0.77 [0.67-0.9]). As with the time-independent analysis, we also find that having completed a booster dose in addition to a primary COVID-19 vaccination sequence does not provide additional protection from developing Long COVID symptoms or being diagnosed with Long COVID over having completed the primary sequence alone (vaccinated and boosted versus vaccinated HR of symptoms 0.96 [0.92-1.01], HR of diagnosis 0.89 [0.76-1.06]) . We find that completing a primary vaccination sequence is associated with a decreased risk of developing Long COVID symptoms or being diagnosed with Long COVID compared with no vaccination regardless of whether vaccination status is modeled as a time-independent or time-dependent covariate. We find a similar protective effect in patients who have completed a primary vaccination sequence and a booster dose when compared to the those who are unvaccinated. However, we do not find evidence for a difference in protective effect between patients who have completed a primary vaccination sequence and a booster dose and those patients who have only completed a primary vaccination sequence. Our results support the growing evidence that having complete a primary vaccination sequence is protective against the development of Long COVID symptoms or the diagnosis of Long COVID.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.28.23289271v1" target="_blank">Effect of vaccination on time till Long COVID, a comparison of two ways to model effect of vaccination and two outcome definitions</a>
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<li><strong>Temporal Trend in Mortality from COVID-19 Associated with Cardiovascular Disease</strong> -
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Background: The COVID-19 pandemic has endured for over three years with over twelve variants afflicting humans worldwide. The impact and longevity of the pandemic has driven the medical community and researchers to identify high-risk populations, yet few studies have explored temporal trends during the pandemic. The objective of this study is to investigate trends in all-cause mortality associated with co-morbid cardiovascular disease (CVD) throughout the consecutive waves of the COVID-19 pandemic. Methods: A retrospective cohort study was conducted on patients with COVID-19 infection who received care at a tertiary care center in Chicago between March 2020 and September 2022. Multivariable logistic regression was used to investigate associations between co-existing CVD (defined as congestive heart failure, myocardial infarction, cerebrovascular disease, peripheral vascular disease) and mortality, adjusting for age, sex, race, and comorbidities defined in the Charlson comorbidity index. Results: The study included 38651 participants (mean age 45 years, 57.6% female, 11.4% with co-existing CVD). All-cause mortality in COVID-19 patients was highest during the Delta wave and remained elevated until the late Omicron wave. Mortality associated with co-existing CVD increased during the early pandemic waves, decreased in the later waves, but remained elevated relative to the overall population. When adjusted for age, sex, and race, all-cause mortality was 2.3-fold higher in patients with co-existing CVD compared to those with non-CVD comorbidities (OR = 2.30, 95% CI 1.95 – 2.62; p < 0.001). Conclusions: While overall mortality rates declined toward the later waves of the pandemic, all-cause mortality associated with CVD remained elevated compared to individuals without CVD.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.26.23289183v1" target="_blank">Temporal Trend in Mortality from COVID-19 Associated with Cardiovascular Disease</a>
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<li><strong>Characterization and Resistance to Mutation of a Single-Channel Multiplex PCR Assay for SARS-CoV-2</strong> -
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Throughout the COVID-19 pandemic, wastewater surveillance has been used worldwide to provide valuable public health data. RT-qPCR is frequently used as a quantitative methodology for wastewater surveillance but is susceptible to mutations in target regions. These mutations may lead to misinterpretation of surveillance data; a drop in signal could be concluded to be a result of lower viral load, when in fact it is caused by reduced detection efficiency. We describe a novel approach to mitigating the impacts of such mutations: monitoring the cumulative signal from two targets (N1 and N2) via independent amplification reactions using identically labeled probes; a single-channel multiplex approach. Using the IDEXX Water SARS-CoV-2 RT-qPCR test, we demonstrate equivalent intra-assay repeatability and quantitative results from the combined N1N2 test when compared to individual N1 and N2 assays. Furthermore, we show that while mutations in B.1.1.529, BA.5.2, and BA.5.2.1 significantly impact the performance of the N1 assay, the impact on the N1N2 assay was negligible, and nearly within acceptable margin of error for technical replicates. These findings demonstrate that a single-channel multiplex approach can be used to improve the robustness of wastewater surveillance and minimize the risk of future mutations leading to unreliable public health data.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.27.23289205v1" target="_blank">Characterization and Resistance to Mutation of a Single-Channel Multiplex PCR Assay for SARS-CoV-2</a>
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<li><strong>The COV50 classifier predicts frailty and future death, independent from SARS-CoV-2 infection</strong> -
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COV50, a urinary proteomic classifier, predicts disease progression and death from SARS-CoV-2 at early stage, suggesting it might predict pre-established vulnerability. This study investigated the value of COV50 in predicting non-COVID-19 associated death. Urinary proteomic data were extracted from the Human Urinary Proteome Database. In the ICU group (n=1719), an increase in the COV50 score of one unit resulted in a 20% higher relative risk of death (adj. HR 1.2 [95% CI 1.17-1.24]). The same increase in COV50 in non-ICU patients (n=7474) resulted in a higher relative risk of 61% (adj. HR 1.61 [95% CI 1.47-1.76]), in line with adjusted meta-analytic HR estimate of 1.55. A higher COV50 scoring was observed in frail patients (p<0.0001). The COV50 classifier is predictive of death, and is associated with frailty suggesting that it detects pre-existing vulnerability. These data may serve as basis for proteomics guided intervention, reducing the risk of death and frailty.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.28.23289257v1" target="_blank">The COV50 classifier predicts frailty and future death, independent from SARS-CoV-2 infection</a>
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<li><strong>Mediators of monocyte chemotaxis and matrix remodeling are associated with the development of fibrosis in patients with COVID-19</strong> -
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Acute respiratory distress syndrome (ARDS) has a fibroproliferative phase that may be followed by pulmonary fibrosis. This has been described in patients with COVID-19 pneumonia, but the underlying mechanisms have not been completely defined. We hypothesized that protein mediators of tissue remodeling and monocyte chemotaxis are elevated in the plasma and endotracheal aspirates of critically ill patients with COVID-19 who subsequently develop radiographic fibrosis. We enrolled COVID-19 patients admitted to the ICU who had hypoxemic respiratory failure, were hospitalized and alive for at least 10 days, and had chest imaging done during hospitalization (n = 119). Plasma was collected within 24h of ICU admission and at 7d. In mechanically ventilated patients, endotracheal aspirates (ETA) were collected at 24h and 48-96h. Protein concentrations were measured by immunoassay. We tested for associations between protein concentrations and radiographic evidence of fibrosis using logistic regression adjusting for age, sex, and APACHE score. We identified 39 patients (33%) with features of fibrosis. Within 24h of ICU admission, plasma proteins related to tissue remodeling (MMP-9, Amphiregulin) and monocyte chemotaxis (CCL-2/MCP-1, CCL-13/MCP-4) were associated with the subsequent development of fibrosis whereas markers of inflammation (IL-6, TNF-α) were not. After 1 week, plasma MMP-9 increased in patients without fibrosis. In ETAs, only CCL-2/MCP-1 was associated with fibrosis at the later timepoint. This cohort study identifies proteins of tissue remodeling and monocyte recruitment that may identify early fibrotic remodeling following COVID-19. Measuring changes in these proteins over time may allow for early detection of fibrosis in patients with COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.28.23289261v1" target="_blank">Mediators of monocyte chemotaxis and matrix remodeling are associated with the development of fibrosis in patients with COVID-19</a>
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<li><strong>Characterization of the SARS-CoV-2 BA.5.5 and BQ.1.1 Omicron Variants in Mice and Hamsters</strong> -
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The continued evolution and emergence of novel SARS-CoV-2 variants has resulted in challenges to vaccine and antibody efficacy. The emergence of each new variant necessitates the need to re-evaluate and refine animal models used for countermeasure testing. Here, we tested a currently circulating SARS-CoV-2 Omicron lineage variant, BQ.1.1, in multiple rodent models including K18-hACE2 transgenic, C57BL/6J, and 129S2 mice, and Syrian golden hamsters. In contrast to a previously dominant BA.5.5 Omicron variant, inoculation of K18-hACE2 mice with BQ.1.1 resulted in a substantial weight loss, a characteristic seen in pre-Omicron variants. BQ.1.1 also replicated to higher levels in the lungs of K18-hACE2 mice and caused greater lung pathology than the BA.5.5 variant. However, C57BL/6J mice, 129S2 mice, and Syrian hamsters inoculated with BQ.1.1 showed no differences in respiratory tract infection or disease compared to animals administered BA.5.5. Airborne or direct contact transmission in hamsters was observed more frequently after BQ.1.1 than BA.5.5 infection. Together, these data suggest that the BQ.1.1 Omicron variant has increased virulence in some rodent species, possibly due to the acquisition of unique spike mutations relative to other Omicron variants.
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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/10.1101/2023.04.28.538747v1" target="_blank">Characterization of the SARS-CoV-2 BA.5.5 and BQ.1.1 Omicron Variants in Mice and Hamsters</a>
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<li><strong>The changing mix of gay bar subtypes after COVID-19 restrictions in the United States, 2017-2023</strong> -
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What was the impact on gay bars of COVID-19 occupancy restrictions? Gay bars had been closing steadily for 30 years before public health authorities shuttered all bars and restaurants in March 2020. Trends are drawn from historic data from printed business guides were supplemented with two national censuses of online business listings for LGBTQ+ bars. Results show a rebound from a nadir of 470 gay bars in Spring 2021 to 803 two years later. Not all bars rebounded: bars serving mostly/only cisgender men plummeted in their share from 44.6% of all gay bars to only 24.2% in Spring 2023. Bars serving men’s kink communities also declined, from 8.5% to 6.6% of all gay bars. Bars serving men and women increased from 44.2% to more than 65.6% of all gay bars, by far the largest gay bar subtype. Lesbian bars, a small share of all gay bars, nevertheless nearly doubled from 15 to 29 establishments to 3.6% of the total. Bars serving people of color experienced a small decline in their share 2019-23. The COVID-19 pandemic marked a dramatic change in the gender composition of gay bars and a slowing rate of decline.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/4uw6j/" target="_blank">The changing mix of gay bar subtypes after COVID-19 restrictions in the United States, 2017-2023</a>
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<li><strong>In Support of Universal Admission Testing for SARS-CoV-2 During Significant Community Transmission</strong> -
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Many hospitals have stopped or are considering stopping universal admission testing for SARS-CoV-2. We discuss reasons why admission testing should still be part of a layered system to prevent hospital-acquired SARS-CoV-2 infections during times of significant community transmission. These include the morbidity of SARS-CoV-2 in vulnerable patients, the predominant contribution of presymptomatic and asymptomatic people to transmission, the high rate of transmission between patients in shared rooms, and the data suggesting surveillance testing is associated with fewer nosocomial infections. Preferences of diverse patient populations, particularly the hardest hit communities, should be surveyed and used to inform prevention measures. Hospitals’ ethical responsibility to protect patients from serious infections should predominate over concerns about costs, labor, and inconvenience. We call for more rigorous data on the incidence and morbidity of nosocomial SARS-CoV-2 infections and more research to help determine when to start, stop, and restart universal admission testing and other prevention measures.
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🖺 Full Text HTML: <a href="https://osf.io/unfz7/" target="_blank">In Support of Universal Admission Testing for SARS-CoV-2 During Significant Community Transmission</a>
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</div></li>
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</ul>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of mRNA-1283.222 Injection Compared With mRNA-1273.222 Injection in Participants ≥12 Years of Age to Prevent COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: mRNA-1283.222; Biological: mRNA-1273.222<br/><b>Sponsor</b>: ModernaTX, 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>Evaluation of the RD-X19 Treatment Device in Individuals With Mild COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Device: RD-X19; Device: Sham<br/><b>Sponsor</b>: EmitBio 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>Postoperative Sugammadex After COVID-19</strong> - <b>Conditions</b>: General Anesthesia; COVID-19<br/><b>Interventions</b>: Drug: Sugammadex Sodium; Drug: neostigmine 50µg/kg + glycopyrollate 0.01mg/kg<br/><b>Sponsor</b>: Korea University Ansan Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study to Determine the Safety and Effectiveness of Azeliragon in the Treatment of Patients Hospitalized for Coronavirus Disease 2019 (COVID-19)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Azeliragon; Drug: Placebo<br/><b>Sponsor</b>: Salim S. Hayek<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>Cognitive-behavioral Therapy for Mental Disorder in COVID-19 Survivors</strong> - <b>Condition</b>: Post Acute COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: mindfulness-based stress reduction (MBSR) and cognitive behavioral therapy (CBT)<br/><b>Sponsor</b>: Azienda Socio Sanitaria Territoriale di Lecco<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>Long COVID-19 Syndrome Lifestyle Intervention Study</strong> - <b>Condition</b>: Long COVID-19 Syndrome<br/><b>Intervention</b>: Dietary Supplement: Low carbohydrate diet intervention<br/><b>Sponsor</b>: University of Southern California<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 Coping and Resilience Intervention for Adolescents</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Behavioral: Coping and Resilience Intervention for Adolescents; Other: Printing materials of Coping and Resilience Intervention for Adolescents<br/><b>Sponsor</b>: Taipei Medical University<br/><b>Enrolling by invitation</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>Effectiveness of Modified Diaphragmatic Training for Gastroesophageal Reflux Disease Post Covid-19</strong> - <b>Conditions</b>: GERD; Post COVID-19 Condition; Diaphragm Issues<br/><b>Interventions</b>: Other: modified diaphragmatic training; Other: standard diaphragmatic training<br/><b>Sponsor</b>: Indonesia University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Telerehabilitation Practice in Long COVID-19 Patients</strong> - <b>Conditions</b>: Long COVID-19; Long COVID; Post COVID-19 Condition; Post-COVID-19 Syndrome; Post-COVID Syndrome<br/><b>Interventions</b>: Behavioral: Telerehabilitation; Behavioral: Standard rehabilitation care<br/><b>Sponsor</b>: Indonesia University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Safety, Tolerability and Pharmacokinetics Study of RAY1216 in Healthy Adult Participants</strong> - <b>Condition</b>: COVID-19 (Coronavirus Disease 2019)<br/><b>Interventions</b>: Drug: RAY1216 dose 1; Drug: RAY1216 dose 2; Drug: RAY1216 dose 3; Drug: RAY1216 dose 4 &ritonavir Drug: RAY1216 dose 5; Drug: RAY1216 dose 6; Drug: RAY1216 dose 7; Drug: RAY1216 dose 8; Drug: RAY1216 dose 9; Drug: RAY1216 dose 10<br/><b>Sponsor</b>: Guangdong Raynovent Biotech Co., Ltd<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>Computerized Training of Attention and Working Memory in Post COVID-19 Patients With Cognitive Complaints</strong> - <b>Conditions</b>: COVID-19; Cognitive Impairment; Cognition Disorder; Memory Disorders; Attention Deficit; Memory Impairment; Memory Loss; Attention Impaired<br/><b>Intervention</b>: Device: RehaCom<br/><b>Sponsor</b>: Erasmus 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>Strategies and Treatments for Respiratory Infections &Amp; Viral Emergencies (STRIVE): Immune Modulation Strategy Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: abatacept infusion; Drug: Placebo group<br/><b>Sponsor</b>: University of Minnesota<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of Silmitasertib (CX-4945) in Healthy Subject</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: CX-4945<br/><b>Sponsor</b>: Senhwa Biosciences, Inc.<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of the Efficacy and Safety of Nano-S1</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Drug: NANOS1 , argent colloïdal ,<br/><b>Sponsor</b>: General Administration of Military Health, Tunisia<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>Digital Mental Health Care for COVID-19 High-Risk Populations - Phase 2</strong> - <b>Conditions</b>: Stigma, Social; Help-Seeking Behavior<br/><b>Interventions</b>: Other: Adjusted Content Intervention; Other: Non-Adjusted Intervention Video<br/><b>Sponsors</b>: Research Foundation for Mental Hygiene, Inc.; Columbia University<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Oridonin inhibits SARS-CoV-2 replication by targeting viral proteinase and polymerase</strong> - COVID-19 has become a global public health crisis since its outbreak in China in December 2019. Currently there are few clinically effective drugs to combat SARS-CoV-2 infection. The main protein (M^(pro)), papain-like protease (PLpro) and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 are involved in the viral replication, and might be prospective targets for anti-coronavirus drug development. Here, we investigated the antiviral activity of oridonin, a natural small-molecule compound,…</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>Advanced Nitric Oxide Generating Nanomedicine for Therapeutic Applications</strong> - Nitric oxide (NO), a gaseous transmitter extensively present in the human body, regulates vascular relaxation, immune response, inflammation, neurotransmission, and other crucial functions. Nitrite donors have been used clinically to treat angina, heart failure, pulmonary hypertension, and erectile dysfunction. Based on NO’s vast biological functions, it further can treat tumors, bacteria/biofilms and other infections, wound healing, eye diseases, and osteoporosis. However, delivering NO 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>Identification of diphenylurea derivatives as novel endocytosis inhibitors that demonstrate broad-spectrum activity against SARS-CoV-2 and influenza A virus both in vitro and in vivo</strong> - Rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) poses enormous challenge in the development of broad-spectrum antivirals that are effective against the existing and emerging viral strains. Virus entry through endocytosis represents an attractive target for drug development, as inhibition of this early infection step should block downstream infection processes, and potentially inhibit viruses sharing the same entry route. In this study,…</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 Mitochondria in Phytochemically Mediated Disease Amelioration</strong> - Mitochondrial dysfunction may cause cell death, which has recently emerged as a cancer prevention and treatment strategy mediated by chemotherapy drugs or phytochemicals. However, most existing drugs cannot target cancerous cells and may adversely affect normal cells via side effects. Mounting studies have revealed that phytochemicals such as resveratrol could ameliorate various diseases with dysfunctional or damaged mitochondria. For instance, resveratrol can regulate mitophagy, inhibit…</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>Fighting cytokine storm and immunomodulatory deficiency: By using natural products therapy up to now</strong> - A novel coronavirus strain (COVID-19) caused severe illness and mortality worldwide from 31 December 2019 to 21 March 2023. As of this writing, 761,071,826 million cases have been diagnosed worldwide, with 6,879,677 million deaths accorded by WHO organization and has spread to 228 countries. The number of deaths is closely connected to the growth of innate immune cells in the lungs, mainly macrophages, which generate inflammatory cytokines (especially IL-6 and IL-1β) that induce "cytokine storm…</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>Interactions of heparin with key glycoproteins of human respiratory syncytial virus</strong> - Introduction: The unexpected surge of respiratory syncytial virus (RSV) cases following pandemic phase of COVID-19 has drawn much public attention. Drawing on the latest antiviral research, revisiting this heightened annual outbreak of respiratory disease could lead to new treatments. The ability of sulfated polysaccharides to compete for a variety of viruses binding to cell surface heparan sulfate, suggests several drugs that might have therapeutic potential for targeting RSV-glycosaminoglycan…</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>Powerful Avidity with a Limited Valency for Virus-Attachment Blockers on DC-SIGN: Combining Chelation and Statistical Rebinding with Structural Plasticity of the Receptor</strong> - The C-type lectin receptor DC-SIGN has been highlighted as the coreceptor for the spike protein of the SARS-CoV-2 virus. A multivalent glycomimetic ligand, Polyman26, has been found to inhibit DC-SIGN-dependent trans-infection of SARS-CoV-2. The molecular details underlying avidity generation in such systems remain poorly characterized. In an effort to dissect the contribution of the known multivalent effects - chelation, clustering, and statistical rebinding - we studied a series of dendrimer…</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>Cognitive inhibition deficit in long COVID-19: An exploratory study</strong> - BACKGROUND AND OBJECTIVES: An increasing number of research studies point toward the importance and prevalence of long-term neurocognitive symptoms following infection with COVID-19. Our objectives were to capture the prevalence of cognitive impairments from 1 to 16 months post-COVID-19 infection, assess the changes in neuropsychological functions over time, and identify factors that can predict long-term deficits in cognition.</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>SNAP@CQD as a promising therapeutic vehicle against HCoVs: an overview</strong> - This report discusses potential therapies for treating human coronaviruses (HCoVs) and their economic impact. Specifically, we explore therapeutics that can support the body’s immune response, including immunoglobulin (Ig)A, IgG and T-cell responses, to inhibit the viral replication cycle and improve respiratory function. We hypothesize that carbon quantum dots conjugated with S-nitroso-N-acetylpenicillamine (SNAP) could be a synergistic alternative cure for treating respiratory injuries caused…</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>GMI, a fungal immunomodulatory protein, ameliorates SARS-CoV-2 envelope protein-induced inflammation in macrophages via inhibition of MAPK pathway</strong> - Clinically, COVID-19 is often accompanied by a severe immune response (cytokine storm) which produces a large number of cytokines, such as TNF-α, IL-6 and IL-12, and consequently causes acute respiratory distress syndrome (ARDS). GMI is a type of fungal immunomodulatory protein that is cloned from Ganoderma microsporum and acts as modulating immunocyte for various inflammatory diseases. This study identifies GMI as a potential anti-inflammatory agent and determines the effects of GMI on 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>Innate immune pathway modulator screen identifies STING pathway activation as a strategy to inhibit multiple families of arbo and respiratory viruses</strong> - RNA viruses continue to remain a threat for potential pandemics due to their rapid evolution. Potentiating host antiviral pathways to prevent or limit viral infections is a promising strategy. Thus, by testing a library of innate immune agonists targeting pathogen recognition receptors, we observe that Toll-like receptor 3 (TLR3), stimulator of interferon genes (STING), TLR8, and Dectin-1 ligands inhibit arboviruses, Chikungunya virus (CHIKV), West Nile virus, and Zika virus to varying degrees….</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>Robust SARS-CoV-2-specific and heterologous immune responses in vaccine-naïve residents of long-term care facilities who survive natural infection</strong> - We studied humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 152 long-term care facility staff and 124 residents over a prospective 4-month period shortly after the first wave of infection in England. We show that residents of long-term care facilities developed high and stable levels of antibodies against spike protein and receptor-binding domain. Nucleocapsid-specific responses were also elevated but waned over time. Antibodies showed stable…</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>Sulfated endospermic nanocellulose crystals prevent the transmission of SARS-CoV-2 and HIV-1</strong> - Biomaterials with antimicrobial activity are gaining attention due to their biodegradability and efficacy in interacting with a wide range of microorganisms. A new cellulose nano-biomaterial, endospermic nanocellulose crystals (ENC) obtained from parenchymal tissue of ivory nut endosperm, has a natural capacity as a universal binder. This feature is enhanced when it is chemically functionalized, and can be exploited in the fight against microbes. We tested the ability of sulfated ENC in aqueous…</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>MasitinibL shows promise as a drug-like analog of masitinib that elicits comparable SARS-Cov-2 3CLpro inhibition with low kinase preference</strong> - SARS-CoV-2 infection has led to several million deaths worldwide and ravaged the economies of many countries. Hence, developing therapeutics against SARS-CoV-2 remains a core priority in the fight against COVID-19. Most of the drugs that have received emergency use authorization for treating SARS-CoV-2 infection exhibit a number of limitations, including side effects and questionable efficacy. This challenge is further compounded by reinfection after vaccination and the high likelihood 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>Recuperative herbal formula Jing Si maintains vasculature permeability balance, regulates inflammation and assuages concomitants of “Long-Covid”</strong> - Coronavirus disease 2019 (COVID-19) is a worldwide health threat that has long-term effects on the patients and there is currently no efficient cure prescribed for the treatment and the prolonging effects. Traditional Chinese medicines (TCMs) have been reported to exert therapeutic effect against COVID-19. In this study, the therapeutic effects of Jing Si herbal tea (JSHT) against COVID-19 infection and associated long-term effects were evaluated in different in vitro and in vivo models. The…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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