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186 lines
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<title>21 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>Accuracy of Expired BinaxNOW Rapid Antigen Tests</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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The widespread existence of expired antigen testing kits in households and potential coronavirus outbreaks necessitate evaluating the reliability of these expired kits. Our study examined BinaxNOW COVID-19 rapid antigen tests 27 months post-manufacture and 5 months past their FDA extended expiration dates, using SARS-CoV-2 variant XBB.1.5 viral stock. We conducted testing at two concentrations: the Limit of Detection (LoD) and 10 times the LoD. 100 expired and unexpired kits were tested at each concentration for a total of 400 antigen tests. At the LoD (2.32x10^2 TCID50/mL), both expired and unexpired tests displayed 100% sensitivity (95% CI 96.38% to 100%), with no statistical difference (95% CI -3.92% to 3.92%). Similarly, at 10 times the LoD, unexpired tests retained 100% sensitivity (95% CI 96.38% to 100%), while expired tests exhibited 99% sensitivity (95% CI 94.61% to 99.99%), demonstrating a statistically insignificant 1% difference (95% CI -2.49% to 4.49%, p=0.56). Expired rapid antigen tests had fainter lines than the unexpired tests at each viral concentration. The expired rapid antigens tests at LoD were only just visible. These findings carry significant implications for waste management, cost efficiency, and supply chain resilience in pandemic readiness efforts. They also provide critical insights for formulating clinical guidelines for interpreting results from expired kits. In light of expert warnings of a potential outbreak of a severity rivaling the Omicron variant, our study underscores the importance of maximizing the utility of expired antigen testing kits in managing future health emergencies.
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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/10.1101/2023.05.17.23290131v1" target="_blank">Accuracy of Expired BinaxNOW Rapid Antigen Tests</a>
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</div></li>
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<li><strong>Bard explains the main content and further development’s potential of “Social identity loss and reverse culture shock: Experiences of international students in China during the COVID-19 pandemic”</strong> -
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<div>
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I have read the article “Social identity loss and reverse culture shock: Experiences of international students in China during the COVID-19 pandemic” by Rameez Raja, Jianfu Ma, Miwei Zhang,corresponding, Xi Yuan Li, Nayef Shabbab Almutairi, and Aeshah Hamdan Almutairi, explained its content through Mindsponge Theory, and indicated how Bayesian Mindsponge Framework (BMF) analytics can be used to develop the study further.
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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/psvxn/" target="_blank">Bard explains the main content and further development’s potential of “Social identity loss and reverse culture shock: Experiences of international students in China during the COVID-19 pandemic”</a>
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</div></li>
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<li><strong>The Federal Reserve’s Response to the Global Financial Crisis and Its Long-Term Impact: An Interrupted Time-Series Natural Experimental Analysis</strong> -
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<div>
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This paper examines the monetary policies the Federal Reserve implemented in response to the Global Financial Crisis. More specifically, it analyzes the Federal Reserve’s quantitative easing (QE) programs, liquidity facilities, and forward guidance operations conducted from 2007 to 2018. The essay’s detailed examination of these policies culminates in an interrupted time-series (ITS) analysis of the long-term causal effects of the QE programs on U.S. inflation and real GDP. The results of this formal design-based natural experimental approach show that the QE operations positively affected U.S. real GDP but did not significantly impact U.S. inflation. Specifically, it is found that, for the 2011Q2-2018Q4 post-QE period, real GDP per capita in the U.S. increased by an average of 231 dollars per quarter relative to how it would have changed had the QE programs not been conducted. Moreover, the results show that, in 2018Q4, ten years after the beginning of the QE programs, real GDP per capita in the U.S. was 14% higher relative to what it would have been during that quarter had there not been the QE programs. These findings contradict Williamson’s (2017) informal natural experimental evidence and confirm the conclusions of VARs and new Keynesian DSGE models that the Federal Reserve’s QE policies positively affected U.S. real GDP. The results suggest that the current U.S. and worldwide high inflation rates are likely not because of the QE programs implemented in response to the financial crisis that accompanied the COVID-19 pandemic. They are likely due to the unprecedentedly large fiscal stimulus packages used, the peculiar nature of the financial downturn itself, the negative supply shocks from the war in Ukraine, or a combination of these factors. To the best of my knowledge, this paper is the first study to measure the macroeconomic effects of QE using a design-based natural experimental approach.
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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/53qbm/" target="_blank">The Federal Reserve’s Response to the Global Financial Crisis and Its Long-Term Impact: An Interrupted Time-Series Natural Experimental Analysis</a>
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</div></li>
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<li><strong>Changes in Transmission and Symptoms of SARS-CoV-2 in United States Households, April 2020-September 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: The natural history of SARS-CoV-2 infection and transmission dynamics may have changed as SARS-CoV-2 has evolved and population immunity has shifted. Methods: Household contacts, enrolled from two multi-site case-ascertained household transmission studies (April 2020-April 2021 and September 2021-September 2022), were followed for 10-14 days after enrollment with daily collection of nasal swabs and/or saliva for SARS-CoV-2 testing and symptom diaries. SARS-CoV-2 virus lineage was determined by whole genome sequencing, with multiple imputation where sequences could not be recovered. Adjusted infection risks were estimated using modified Poisson regression. Findings: 858 primary cases with 1473 household contacts were examined. Among unvaccinated household contacts, the infection risk adjusted for presence of prior infection and age was 58% (95% confidence interval [CI]: 49-68%) in households currently exposed to pre-Delta lineages and 90% (95% CI: 74-100%) among those exposed to Omicron BA.5 (detected May - September 2022). The fraction of infected household contacts reporting any symptom was similarly high between pre-Delta (86%, 95% CI: 81-91%) and Omicron lineages (77%, 70-85%). Among Omicron BA.5-infected contacts, 48% (41-56%) reported fever, 63% (56-71%) cough, 22% (17-28%) shortness of breath, and 20% (15-27%) loss of/change in taste/smell. Interpretation: The risk of infection among household contacts exposed to SARS-CoV-2 is high and increasing with more recent SARS-CoV-2 lineages. This high infection risk highlights the importance of vaccination to prevent severe disease. Funding: Funded by the Centers for Disease Control and Prevention and the Food and Drug Administration.
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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/10.1101/2023.05.18.23290185v1" target="_blank">Changes in Transmission and Symptoms of SARS-CoV-2 in United States Households, April 2020-September 2022</a>
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</div></li>
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<li><strong>State Variation in Neighborhood COVID-19 Burden: Findings from the COVID Neighborhood Project</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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A lack of fine, spatially-resolute case data for the U.S. has prevented the examination of how COVID-19 burden has been distributed across neighborhoods, a known geographic unit of both risk and resilience, and is hampering efforts to identify and mitigate the long-term fallout from COVID-19 in vulnerable communities. Using spatially-referenced data from 21 states at the ZIP code or census tract level, we documented how the distribution of COVID-19 at the neighborhood-level varies significantly within and between states. The median case count per neighborhood (IQR) in Oregon was 3,608 (2,487) per 100,000 population, indicating a more homogenous distribution of COVID-19 burden, whereas in Vermont the median case count per neighborhood (IQR) was 8,142 (11,031) per 100,000. We also found that the association between features of the neighborhood social environment and burden varied in magnitude and direction by state. Our findings underscore the importance of local contexts when addressing the long-term social and economic fallout communities will face from COVID-19.
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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/10.1101/2023.05.19.23290222v1" target="_blank">State Variation in Neighborhood COVID-19 Burden: Findings from the COVID Neighborhood Project</a>
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</div></li>
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<li><strong>Assessing the effect of zoo closure on the soundscape using multiple measures</strong> -
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<div>
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The zoo soundscape has a number of important implications for animal welfare, management, and conservation. However, despite its importance, the zoo soundscape is yet to be examined in depth using multiple measures. Consistent human presence can influence the zoo soundscape. However, it is difficult to determine the specific impact of human presence, as visitors are usually present during the day when animals are active. The COVID-19 lockdown in 2020 provided a unique opportunity to study zoo soundscapes in the absence of visitors. We compared the sound environment during the 2020 closure period to a comparable open period in 2019 across three zoo aviaries, examining broad band frequency measures of sound pressure levels, sound pressure levels in defined frequency bands, and acoustic indices (Acoustic Complexity Index and Normalized Difference Soundscape Index) to describe the zoo soundscape. Acoustic indices have not, to our knowledge, previously been used in the zoo setting, although they may provide a useful metric to assess sound disturbance. Therefore, we also used this natural experiment to explore how successful these measures may be in assessing disturbances in captive environments. We found a significant effect of human presence on the sound environment; aviaries were generally quieter with less low frequency noise and with a greater proportion of biotic sound during the 2020 zoo closure period. We argue that NDSI could be a useful index for determining anthropogenic disturbance in zoos, although further information on how it is influenced by additional factors, such as human speech, would be beneficial. The use of multiple measures to assess the sound environment in zoos can provide additional information beyond 'loudness', such as frequencies where sound energy is concentrated and characteristics of the soundscape, which could be used to better target management and mitigation.
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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/10.1101/2023.05.19.540934v1" target="_blank">Assessing the effect of zoo closure on the soundscape using multiple measures</a>
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</div></li>
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<li><strong>A scoping review of behavioural science approaches and frameworks for health protection and emergency response</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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Aim: Rapid intervention development, implementation and evaluation is required for emergency public health contexts, such as the recent COVID-19 pandemic. A novel Agile Co-production and Evaluation (ACE) framework has been developed to assist this endeavour in future public health emergencies. This scoping review aimed to map available behavioural science resources that can be used to develop and evaluate public health guidance, messaging, and interventions in emergency contexts onto components of ACE: rapid development and implementation, co-production with patients or the public including seldom heard voices from diverse communities, and inclusion of evaluation. Methods: A scoping review methodology was used. Searches were run on MEDLINE, EMBASE, PsychInfo, and Google, with search terms covering emergency response and behavioural science. Papers published since 2014 and which discussed a framework or guidance for using behavioural science in response to a public health emergency, were included. A narrative synthesis was conducted. Results: Seventeen records were included in the synthesis. The records covered a range of emergency contexts, the most frequent of which were COVID-19 (n=7) and non-specific emergencies (n=4). One record evaluated existing tools, six proposed new tools, and ten described existing tools. Commonly used tools included the Behavioural Change Wheel, Capability, Opportunity, and Motivation Behaviour model (COM-B model) and social identity theory. Three records discuss co-production with the target audience and consideration of diverse populations. Four records incorporate rapid testing, evaluation, or validation methods. Six records state that their tool is designed to be implemented rapidly. No records cover all components of ACE. Conclusion: We recommend that future research explores how to create guidance involving rapid implementation, co-production with patients or the public including seldom-heard voices from diverse communities, and evaluation. Keywords: behavioural insights, emergency response, health protection.
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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/10.1101/2023.05.19.23290226v1" target="_blank">A scoping review of behavioural science approaches and frameworks for health protection and emergency response</a>
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</div></li>
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<li><strong>A systematic narrative review of coroners’ prevention of future deaths reports (PFDs): a potential metric for patient safety in hospitals</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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Patient harm due to unsafe healthcare is widespread, potentially devastating, and often preventable. Hoping to eliminate avoidable harms, the World Health Organization (WHO) published the Global Patient Safety Action Plan in July 2021. The UK9s National Health Service relies on several measures, including “never events”, “serious incidents”, patient safety events, and coroners9 prevention of future death reports (PFDs) to monitor healthcare quality and safety. We conducted a systematic narrative review of PubMed and medRxiv on 19 February 2023 to explore the strengths and limitations of coroners9 PFDs and whether they could be a safety metric to help meet the WHO9s Global Patient Safety Action Plan. We identified 17 studies that investigated a range of PFDs, including preventable deaths involving medicines and an assessment during the COVID-19 pandemic. We found that PFDs offered important information that could support hospitals to improve patient safety and prevent deaths. However, inconsistent reporting, low response rates to PFDs, and difficulty in accessing, analysing, and monitoring PFDs limited their use and adoption as a patient safety metric for hospitals. To fulfil the potential of PFDs, a national system is required that develops guidelines, sanctions failed responses, and embeds technology to encourage the prevention of future deaths.
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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/10.1101/2023.05.19.23290187v1" target="_blank">A systematic narrative review of coroners’ prevention of future deaths reports (PFDs): a potential metric for patient safety in hospitals</a>
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</div></li>
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<li><strong>Assessing changes in incubation period, serial interval, and generation time of SARS-CoV-2 variants of concern: a systematic review and meta-analysis</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: After the first COVID-19 wave caused by the ancestral lineage, the pandemic has been fueled from the continuous emergence of new SARS-CoV-2 variants. Understanding key time-to-event periods for each emerging variant of concern is critical as it can provide insights into the future trajectory of the virus and help inform outbreak preparedness and response planning. Here, we aim to examine how the incubation period, serial interval, and generation time have changed from the ancestral SARS-CoV-2 lineage to different variants of concern. Methods: We conducted a systematic review and meta-analysis that synthesized the estimates of incubation period, serial interval, and generation time (both realized and intrinsic) for the ancestral lineage, Alpha, Beta, and Omicron variants of SARS-CoV-2. Results: Our study included 274 records obtained from 147 household studies, contact tracing studies or studies where epidemiological links were known. With each emerging variant, we found a progressive shortening of each of the analyzed key time-to-event periods. Specifically, we found that Omicron had the shortest pooled estimates for the incubation period (3.63 days, 95%CI: 3.25-4.02 days), serial interval (3.19 days, 95%CI: 2.95-3.43 days), and realized generation time (2.96 days, 95%CI: 2.54-3.38 days) whereas the ancestral lineage had the highest pooled estimates for each of them. We also observed shorter pooled estimates for the serial interval compared to the incubation period across the virus lineages. We found considerable heterogeneities (I2 > 80%) when pooling the estimates across different virus lineages, indicating potential unmeasured confounding from population factors (e.g., social behavior, deployed interventions). Conclusion: Our study supports the importance of conducting contact tracing and epidemiological investigations to monitor changes in SARS-CoV-2 transmission patterns. Our findings highlight a progressive shortening of the incubation period, serial interval, and generation time, which can lead to epidemics that spread faster, with larger peak incidence, and harder to control. We also consistently found a shorter serial interval than incubation period, suggesting that a key feature of SARS-CoV-2 is the potential for pre-symptomatic transmission. These observations are instrumental to plan for future COVID-19 waves. Keywords: COVID-19, variants of concern, incubation period, serial interval, realized generation time, intrinsic generation time, systematic review, meta-analysis
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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/10.1101/2023.05.19.23290208v1" target="_blank">Assessing changes in incubation period, serial interval, and generation time of SARS-CoV-2 variants of concern: a systematic review and meta-analysis</a>
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</div></li>
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<li><strong>Enhanced Airway Epithelial Response to SARS-CoV-2 Infection in Children is Critically Tuned by the Cross-Talk Between Immune and Epithelial Cells</strong> -
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<div>
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To cope with novel virus infections to which no prior adaptive immunity exists, the body strongly relies on the innate immune system. In such cases, including infections with SARS-CoV-2, children tend to fair better than adults. In the context of COVID-19, it became evident that a rapid interferon response at the site of primary infection is key for successful control of the virus and prevention of severe disease. The airway epithelium of children was shown to exhibit a primed state already at homeostasis and to respond particularly well to SARS-CoV-2 infection. However, the underlying mechanism for this priming remained elusive. Here we show that interactions between airway mucosal immune cells and epithelial cells are stronger in children, and via cytokine-mediated signaling lead to IRF-1-dependent upregulation of the viral sensors RIG-I and MDA5. Based on a cellular in vitro model we show that stimulated human peripheral blood mononuclear cells (PBMC) can induce a robust interferon-beta response towards SARS-CoV-2 in a lung epithelial cell line otherwise unresponsive to this virus. This is mediated by type I interferon, interferon-gamma and TNF, and requires induction of both, RIG-I and MDA5. In single cell-analysis of nasal swab samples the same cytokines are found to be elevated in mucosal immune cells of children, correlating with elevated epithelial expression of viral sensors. In vitro analysis of PBMC derived from healthy adolescents and adults confirm that immune cells of younger individuals show increased cytokine production and potential to prime epithelial cells. In co-culture with SARS-CoV-2-infected A549 cells, PBMC from adolescents significantly enhance the antiviral response. Taken together, our study suggests that higher numbers and a more vigorous activity of innate immune cells in the airway mucosa of children tune the set-point of the epithelial antiviral system. This likely is a major contributor to the robust immune response to SARS-CoV-2 in children. Our findings shed light on the molecular underpinnings of the stunning resilience of children towards severe COVID-19, and may propose a novel concept for immunoprophylactic treatments.
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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/10.1101/2023.05.17.541103v1" target="_blank">Enhanced Airway Epithelial Response to SARS-CoV-2 Infection in Children is Critically Tuned by the Cross-Talk Between Immune and Epithelial Cells</a>
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</div></li>
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<li><strong>Uncovering strain- and age-dependent differences in innate immune response to SARS-CoV-2 infection in nasal epithelia using 10X single-cell sequencing</strong> -
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<div>
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Assessing the impact of SARS-CoV-2 variants on the host is crucial with continuous emergence of new variants. We employed single-cell sequencing to investigate host transcriptomic response to ancestral and Alpha-strain SARS-CoV-2 infections within air-liquid-interface human nasal epithelial cells from adults and adolescents. Strong innate immune responses were observed across lowly-infected and bystander cell-types, and heightened in Alpha-infection. Contrastingly, the innate immune response of highly-infected cells was comparable to mock-control cells. Alpha highly-infected cells showed increased expression of protein refolding genes compared with ancestral-strain-infected adolescent cells. Oxidative phosphorylation- and translation-related genes were down-regulated in bystander cells versus infected and mock-control cells, suggesting that the down-regulation is protective and up-regulation supports viral activity. Infected adult cells revealed up-regulation of these pathways compared with infected adolescents, implying enhanced pro-viral states in infected adults. Overall, this highlights the complexity of cell-type-, age- and viral-strain-dependent host epithelial responses to SARS-CoV-2 and the value of air-liquid-interface cultures.
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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/10.1101/2023.03.04.531075v2" target="_blank">Uncovering strain- and age-dependent differences in innate immune response to SARS-CoV-2 infection in nasal epithelia using 10X single-cell sequencing</a>
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</div></li>
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<li><strong>Structure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2</strong> -
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<div>
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Proline is widely known as the only proteogenic amino acid with a secondary amine. In addition to its crucial role in protein structure, the secondary amino acid modulates neurotransmission and regulates the kinetics of signaling proteins. To understand the structural basis of proline import, we solved the structure of the proline transporter SIT1 in complex with the COVID-19 viral receptor ACE2 by cryo-electron microscopy. The structure of pipecolate-bound SIT1 reveals the specific sequence requirements for proline transport in the SLC6 family and how this protein excludes amino acids with extended side chains. By comparing apo and substrate-bound SIT1 states, we also identify the structural changes which link substrate release and opening of the cytoplasmic gate, and provide an explanation for how a missense mutation in the transporter causes iminoglycinuria.
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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/10.1101/2023.05.17.541173v1" target="_blank">Structure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2</a>
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</div></li>
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<li><strong>Marginated aberrant red blood cells induce pathologic vascular stress fluctuations in a computational model of hematologic disorders</strong> -
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<div>
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Red blood cell (RBC) disorders affect billions worldwide. While alterations in the physical properties of aberrant RBCs and associated hemodynamic changes are readily observed, in conditions such as sickle cell disease and iron deficiency, RBC disorders can also be associated with vascular dysfunction. The mechanisms of vasculopathy in those diseases remain unclear and scant research has explored whether biophysical alterations of RBCs can directly affect vascular function. Here we hypothesize that the purely physical interactions between aberrant RBCs and endothelial cells, due to the margination of stiff aberrant RBCs, play a key role in this phenomenon for a range of disorders. This hypothesis is tested by direct simulations of a cellular scale computational model of blood flow in sickle cell disease, iron deficiency anemia, COVID-19, and spherocytosis. We characterize cell distributions for normal and aberrant RBC mixtures in straight and curved tubes, the latter to address issues of geometric complexity that arise in the microcirculation. In all cases aberrant RBCs strongly localize near the vessel walls (margination) due to contrasts in cell size, shape, and deformability from the normal cells. In the curved channel, the distribution of marginated cells is very heterogeneous, indicating a key role for vascular geometry. Finally, we characterize the shear stresses on the vessel walls; consistent with our hypothesis, the marginated aberrant cells generate large transient stress fluctuations due to the high velocity gradients induced by their near-wall motions. The anomalous stress fluctuations experienced by endothelial cells may be responsible for the observed vascular inflammation.
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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/10.1101/2023.05.16.541016v1" target="_blank">Marginated aberrant red blood cells induce pathologic vascular stress fluctuations in a computational model of hematologic disorders</a>
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</div></li>
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<li><strong>CParty: Conditional partition function for density-2RNA pseudoknots</strong> -
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<div>
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RNA molecules fold into biologically important functional structures. Efficient dynamic programming RNA (secondary) structure prediction algorithms restrict the the search space to evade NP-hardness of general pseudoknot prediction. While such prediction algorithms can be extended to provide a stochastic view on RNA ensembles, they are either limited to pseudoknot-free structures or extremely complex. To overcome this dilemma, we follow the hierarchical folding hypothesis, i.e. the bio-physically well-motivated assumption that non-crossing structures fold relatively fast prior to the formation of pseudoknot interactions. Thus, we efficiently compute the conditional partition function (CPF) given a non-crossing structure G for a subset of pseudoknotted stuctures i.e. density-2 structures G {cup} G' for non-crossing disjoint G'. Notably, this enables sampling from the hierarchical distribution P (G'|G). As our main contribution, we devise the algorithm CParty, which transfers the dynamic programming scheme of HFold to a partition function variant by for the first time de-ambiguating its decomposition of density-2 structures. Compared to the only other available pseudoknot partition function algorithm, which covers simple pseudoknots, our method covers a much larger structure class; at the same time, it is significantly more efficient (reducing the time as well as the space complexity by a quadratic factor). Summarizing, we provide a highly efficient (cubic time) algorithm for the stochastic analysis of pseudoknotted RNAs, which enables novel applications. For example, we discuss how the CPF for a pseudoknotted therapeutic target in SARS-CoV-2 provides insights into RNA structure formation kinetic paths.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.16.541023v1" target="_blank">CParty: Conditional partition function for density-2RNA pseudoknots</a>
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</div></li>
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<li><strong>Composite interventions on outcomes of severely and critically ill patients with COVID-19 in Shanghai, China</strong> -
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Abstract Background: The sixty-day effects of initial composite interventions for the treatment of severely and critically ill patients with COVID-19 are not fully assessed. Methods: Using a bayesian piecewise exponential model, we analyzed the 60-day mortality, health-related quality of life (HRQoL) and disability in 1082 severely and critically patients with COVID-19 between December 8, 2022 and February 9, 2023 in Shanghai, China. The final 60-day follow-up was completed on April 10, 2023. Results: Among 1082 patients (mean age, 78.0 years), 421 [38.9%] women), 139 patients (12.9%) died within 60 days. Azvudine had a 99.8% probability of improving 2-month survival (adjusted HR, 0.44 [95% credible interval, 0.24-0.79]) and Paxlovid had a 91.9% probability of improving 2-month survival (adjusted HR, 0.71 [95% credible interval, 0.44-1.14]) compared with the control. IL-6 receptor antagonist, Baricitinib, and a-thymosin each had a high probability of benefit (99.5%, 99.4%, and 97.5%, respectively) compared to their controls, while the probability of trail-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.8%; HR, 1.64 [95% CrI, 1.06-2.50]), and glucocorticoid (91.4%; HR, 1.20 [95% CrI, 0.71-2.16]). Paxlovid, Azvudine and therapeutic anticoagulation showed significant reduction in disability (p<0.05) Conclusions: Among severely and critically ill patients with COVID-19 who received 1 or more therapeutic interventions, treatment with Azvudine had a high probability of improved 60-day mortality compared with the control, indicating its potential in resource-limited scenario. Treatment with IL-6 receptor antagonist, Baricitinib, and a-thymosin also had high probabilities of benefit of improving 2-month survival, among which a-thymosin could improve HRQoL. Treatment with Paxlovid, Azvudine and therapeutic anticoagulation could significantly reduce disability at day 60. Keyword: COVID-19; Azvudine; Paxlovid; Interleukin-6 receptor antagonist; Baricitinib, α-thymosin, Intravenous immunoglobulin
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.10.23289325v3" target="_blank">Composite interventions on outcomes of severely and critically ill patients with COVID-19 in Shanghai, China</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>The Standard of Care Combined With Glucocorticoid in Elderly People With Mild or Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Glucocorticoid<br/><b>Sponsor</b>: Huashan 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>Investigation of the Effect on Cognitive Skills of COVID-19 Survivors</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: green walking and intelligence gam<br/><b>Sponsors</b>: Bayburt University; Karadeniz Technical 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>Conducting Clinical Trials of the Medicine “Rutan Tablets 0.1g” No. 10 in the Complex Therapy of COVID-19</strong> - <b>Condition</b>: Patients With COVID-19<br/><b>Interventions</b>: Drug: The drug “Rutan 0.1”.; Other: Basic treatment<br/><b>Sponsor</b>: Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan<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>Arginine Replacement Therapy in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Arginine Hydrochloride<br/><b>Sponsor</b>: Emory 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>Effectiveness of a Second COVID-19 Vaccine Booster in Chinese Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Intramuscularly administered Ad5-nCoV vaccine; Biological: Aerosolized Ad5-nCoV; Biological: DelNS1-2019-nCoV-RBD-OPT1; Biological: SYS6006<br/><b>Sponsor</b>: Jiangsu Province Centers 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>Studying the Efficiency of the Natural Preparation Rutan in Children in the Treatment of COVID-19, ARVI</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Interventions</b>: Drug: Rutan 25 mg; Other: Control group<br/><b>Sponsor</b>: Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan<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>A Pilot Study Evaluating the Efficacy of the Vielight Neuro RX Gamma in the Treatment of Post COVID-19 Cognitive Impairment</strong> - <b>Condition</b>: Post COVID-19 Cognitive Impairment<br/><b>Interventions</b>: Device: Vielight Neuro RX Gamma active device; Device: Vielight Neuro RX Gamma sham device<br/><b>Sponsor</b>: Vielight 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>PAxlovid loNg cOvid-19 pRevention triAl With recruitMent In the Community in Norway</strong> - <b>Conditions</b>: Post COVID-19 Condition, Unspecified; SARS-CoV2 Infection; COVID-19<br/><b>Interventions</b>: Drug: Nirmatrelvir/ritonavir; Drug: Placebo<br/><b>Sponsors</b>: Haukeland University Hospital; University of Bergen<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>Use of a Hypochlorous Acid Spray Solution in the Treatment of COVID-19 Patients : COVICONTROL Study .</strong> - <b>Condition</b>: SARS CoV 2 Infection<br/><b>Interventions</b>: Other: Spray with Hypochlorous Acid Group; Other: Spray with Placebo Group<br/><b>Sponsor</b>: University of Monastir<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>Role of Vit-D Supplementation on BioNTech, Pfizer Vaccine Side Effect and Immunoglobulin G Response</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Intervention</b>: Combination Product: Vitamin-D<br/><b>Sponsor</b>: Sulaimany Polytechnic 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>Telerehabilitation Program and Detraining in Patients With Post-COVID-19 Sequelae</strong> - <b>Condition</b>: COVID-19 Acute Respiratory Distress Syndrome<br/><b>Intervention</b>: Other: Telerehabilitation program<br/><b>Sponsor</b>: Campus docent Sant Joan de Déu-Universitat de Barcelona<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>COVID-19 Vaccine Uptake Amongst Underserved Populations in East London</strong> - <b>Conditions</b>: COVID-19; Influenza; Vaccination Refusal<br/><b>Intervention</b>: Device: Patient Engagement tool<br/><b>Sponsors</b>: Queen Mary University of London; Social Action for Health<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>REVERSE-Long COVID-19 With Baricitinib Pilot Study</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>: Drug: Baricitinib 4 MG<br/><b>Sponsors</b>: Vanderbilt University Medical Center; Emory University; University of California, San Francisco; University of Minnesota; Vanderbilt University; Yale 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>Post Covid-19 Dysautonomia Rehabilitation Randomized Controlled Trial</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome; Dysautonomia<br/><b>Interventions</b>: Procedure: Rehabilitation; Procedure: Standard of Care<br/><b>Sponsors</b>: Evangelismos Hospital; National and Kapodistrian University of Athens; LONG COVID GREECE; 414 Military Hospital of Special Diseases<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exercise for Health in Patients With Post-acute Sequelae of COVID-19</strong> - <b>Condition</b>: Long COVID<br/><b>Intervention</b>: Other: Rehabilitation program<br/><b>Sponsors</b>: Campus docent Sant Joan de Déu-Universitat de Barcelona; Hospital de Mataró; University of Barcelona<br/><b>Active, not 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>Optimization, and biological evaluation of 3-O-β-chacotriosyl betulinic acid amide derivatives as novel small-molecule Omicron</strong> - SARS-CoV-2 Omicron viruses possess a high antigenic shift, and the approved anti-SARS-CoV-2 drugs are extremely limited, which makes the development of new antiviral drugs for the clinical treatment and prevention of SARS-CoV-2 outbreaks imperative. We have previously discovered a new series of markedly potent small-molecule inhibitors of SARS-CoV-2 virus entry, exampled by the hit compound 2. Here, we report a further study of bioisosteric replacement of the eater linker at the C-17 position 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>Synthetic and natural guanidine derivatives as antitumor and antimicrobial agents: A review</strong> - Guanidines are fascinating small nitrogen-rich organic compounds, which have been frequently associated with a wide range of biological activities. This is mainly due to their interesting chemical features. For these reasons, for the past decades, researchers have been synthesizing and evaluating guanidine derivatives. In fact, there are currently on the market several guanidine-bearing drugs. Given the broad panoply of pharmacological activities displayed by guanidine compounds, in this review,…</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>Dose-response and type-dependent effects of antiviral drugs in anaerobic digestion of waste-activated sludge for biogas production</strong> - In the context of the COVID-19 pandemic, antiviral drugs (AVDs) were heavily excreted into wastewater and subsequently enriched in sewage sludge due to their widespread use. The potential ecological risks of AVDs have attracted increasing attention, but information on the effects of AVDs on sludge anaerobic digestion (AD) is limited. In this study, two typical AVDs (lamivudine and ritonavir) were selected to investigate the responses of AD to AVDs by biochemical methane potential tests. 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>Potential role of tirzepatide towards Covid-19 infection in diabetic patients: a perspective approach</strong> - In Covid-19, variations in fasting blood glucose are considered a distinct risk element for a bad prognosis and outcome in Covid-19 patients. Tirazepatide (TZT), a dual glucagon-like peptide-1 (GLP-1)and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist may be effective in managing Covid-19-induced hyperglycemia in diabetic and non-diabetic patients. The beneficial effect of TZT in T2DM and obesity is related to direct activation of GIP and GLP-1 receptors with subsequent…</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>Heat waves accelerate the spread of infectious diseases</strong> - COVID-19 pandemic appeared summer surge in 2022 worldwide and this contradicts its seasonal fluctuations. Even as high temperature and intense ultraviolet radiation can inhibit viral activity, the number of new cases worldwide has increased to >78% in only 1 month since the summer of 2022 under unchanged virus mutation influence and control policies. Using the attribution analysis based on the theoretical infectious diseases model simulation, we found the mechanism of the severe COVID-19…</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>Dextran sulfate from <em>Leuconostoc mesenteroides</em> B512F exerts potent antiviral activity against SARS-CoV-2 <em>in vitro</em> and <em>in vivo</em></strong> - The emergent human coronavirus SARS-CoV-2 and its resistance to current drugs makes the need for new potent treatments for COVID-19 patients strongly necessary. Dextran sulfate (DS) polysaccharides have long demonstrated antiviral activity against different enveloped viruses in vitro. However, their poor bioavailability has led to their abandonment as antiviral candidates. Here, we report for the first time the broad-spectrum antiviral activity of a DS-based extrapolymeric substance produced by…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The novel hyaluronic acid granular hydrogel attenuates osteoarthritis progression by inhibiting the TLR-2/NF-κB signaling pathway through suppressing cellular senescence</strong> - In patients with mild osteoarthritis (OA), two to four monthly injections are required for 6 months due to the degradation of hyaluronic acid (HA) by peroxidative cleavage and hyaluronidase. However, frequent injections may lead to local infection and also cause inconvenience to patients during the COVID-19 pandemic. Herein, we developed a novel HA granular hydrogel (n-HA) with improved degradation resistance. The chemical structure, injectable capability, morphology, rheological properties,…</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>Biochemical and HDX Mass Spectral Characterization of the SARS-CoV-2 Nsp1 Protein</strong> - A major challenge in defining the pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is to better understand virally encoded multifunctional proteins and their interactions with host factors. Among the many proteins encoded by the positive-sense, single-stranded RNA genome, nonstructural protein 1 (Nsp1) stands out due to its impact on several stages of the viral replication cycle. Nsp1 is the major virulence factor that inhibits mRNA translation. Nsp1 also…</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>Organoid modeling of lung-resident immune responses to SARS-CoV-2 infection</strong> - Tissue-resident immunity underlies essential host defenses against pathogens, but analysis in humans has lacked in vitro model systems where epithelial infection and accompanying resident immune cell responses can be observed en bloc. Indeed, human primary epithelial organoid cultures typically omit immune cells, and human tissue resident-memory lymphocytes are conventionally assayed without an epithelial infection component, for instance from peripheral blood, or after extraction from organs….</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>Optimization of urban emergency support material distribution under major public health emergencies based on improved sparrow search algorithm</strong> - The outbreak of major public health emergencies such as the coronavirus epidemic has put forward new requirements for urban emergency management procedures. Accuracy and effective distribution model of emergency support materials, as an effective tool to inhibit the deterioration of the public health sector, have gradually become a research hotspot. The distribution of urban emergency support devices, under the secondary supply chain structure of “material transfer center-demand point,” which…</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>Passive swab versus grab sampling for detection of SARS-CoV-2 markers in wastewater</strong> - Early detection of the COVID-19 virus, SARS-CoV-2, is key to mitigating the spread of new outbreaks. Data from individual testing is increasingly difficult to obtain as people conduct non-reported home tests, defer tests due to logistics or attitudes, or ignore testing altogether. Wastewater based epidemiology is an alternative method for surveilling a community while maintaining individual anonymity; however, a problem is that SARS-CoV-2 markers in wastewater varies throughout the day….</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>Oxalic acid blocked the binding of spike protein from SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variants to human angiotensin-converting enzymes 2</strong> - An epidemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. Moreover, the emergence of SARS-CoV-2 variants of concern, such as Delta and Omicron, has seriously challenged the application of current therapeutics including vaccination and drugs. Relying on interaction of spike protein with receptor angiotensin-converting enzymes 2 (ACE2), SARS-CoV-2 successfully invades to the host cells, which indicates a…</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>Antifungal Activity and Potential Action Mechanism of Allicin against Trichosporon asahii</strong> - Trichosporon asahii is an emerging opportunistic pathogen that causes potentially fatal disseminated trichosporonosis. The global prevalence of coronavirus disease 2019 (COVID-19) poses an increasing fungal infection burden caused by T. asahii. Allicin is the main biologically active component with broad-spectrum antimicrobial activity in garlic. In this study, we performed an in-depth analysis of the antifungal characteristics of allicin against T. asahii based on physiological, cytological,…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 Nucleocapsid Protein Is a Potential Therapeutic Target for Anticoronavirus Drug Discovery</strong> - SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, is a highly contagious positive-sense RNA virus. Its explosive community spread and the emergence of new mutant strains have created palpable anxiety even in vaccinated people. The lack of effective anticoronavirus therapeutics continues to be a major global health concern, especially due to the high evolution rate of SARS-CoV-2. The nucleocapsid protein (N protein) of SARS-CoV-2 is highly conserved and involved in diverse processes 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>Six-month immune responses to mRNA-1273 Vaccine in cART-treated late presenter people living with HIV according to previous SARS-CoV-2 Infection</strong> - CONCLUSIONS: Altogether, these findings support the need for additional vaccine doses in PLWH with a history of advanced immune depression and poor immune recovery on effective cART.</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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