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<title>22 March, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>The RBPome of influenza A virus mRNA reveals a role for TDP-43 in viral replication</strong> -
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Recent technical advances have significantly improved our understanding of the RNA-binding protein (RBP) repertoire present within eukaryotic cells, with a particular focus on the RBPs that interact with cellular polyadenylated mRNAs. However, recent studies utilising the same technologies have begun to tease apart the RBP interactome of viral mRNAs, notably SARS-CoV-2, revealing both similarities and differences between the RBP profiles of viral and cellular mRNAs. Herein, we comprehensively identified the RBPs that associate with the NP mRNA of an influenza A virus. Moreover, we provide evidence that the viral polymerase is essential for the recruitment of RPBs to viral mRNAs through direct polymerase-RBP interactions during transcription. We show that loss of TDP-43, which associates with the viral mRNAs, results in lower levels of viral mRNAs within infected cells, and a decreased yield of infectious viral particles. Overall, our results uncover an important role for TDP-43 in the influenza A virus replication cycle via a direct interaction with viral mRNAs, and point to a role of the viral polymerase in orchestrating the assembly of viral mRNPs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.21.533609v1" target="_blank">The RBPome of influenza A virus mRNA reveals a role for TDP-43 in viral replication</a>
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<li><strong>SARS-CoV-2 infection activates endogenous retroviruses of the LTR69 subfamily</strong> -
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Accumulating evidence suggests that endogenous retroviruses (ERVs) play an important role in the host response to infection and the development of disease. By combining RNA- and ChIP-sequencing analyses with RT-qPCR, we show that SARS-CoV-2 infection induces the LTR69 subfamily of ERVs, both in vitro and in vivo. Using functional assays, we identified one SARS-CoV-2-activated LTR69 locus, termed Dup69, which exhibits enhancer activity and is responsive to the transcription factors IRF3 and p65/RelA. LTR69-Dup69 is located about 500 bp upstream of a long non-coding RNA gene (ENSG00000289418) and within the PTPRN2 gene encoding a diabetes-associated autoantigen. Both ENSG00000289418 and PTPRN2 showed a significant increase in expression upon SARS-CoV-2 infection. Thus, our study sheds light on the interplay of exogenous with endogenous viruses and helps to understand how ERVs regulate gene expression during infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.21.533610v1" target="_blank">SARS-CoV-2 infection activates endogenous retroviruses of the LTR69 subfamily</a>
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<li><strong>Nasopharyngeal Angiotensin Converting Enzyme 2 (ACE2) Expression as a Risk-Factor for SARS-CoV-2 Transmission in Concurrent Hospital Associated Outbreaks</strong> -
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Background: Widespread human-to-human transmission of the severe acute respiratory syndrome coronavirus two (SARS-CoV-2) stems from a strong affinity for the cellular receptor angiotensin converting enzyme two (ACE2). We investigate the relationship between a patient9s nasopharyngeal ACE2 transcription and secondary transmission within a series of concurrent hospital associated SARS-CoV-2 outbreaks in British Columbia, Canada. Methods: Epidemiological case data from the outbreak investigations was merged with public health laboratory records and viral lineage calls, from whole genome sequencing, to reconstruct the concurrent outbreaks using infection tracing transmission network analysis. ACE2 transcription and RNA viral load were measured by quantitative real-time polymerase chain reaction. The transmission network was resolved to calculate the number of potential secondary cases. Bivariate and multivariable analyses using Poisson and Negative Binomial regression models was performed to estimate the association between ACE2 transcription the number of SARS-CoV-2 secondary cases. Results: The infection tracing transmission network provided n = 76 potential transmission events across n = 103 cases. Bivariate comparisons found that on average ACE2 transcription did not differ between patients and healthcare workers (P = 0.86). High ACE2 transcription was observed in 98.6% of transmission events, either the primary or secondary case had above average ACE2. Multivariable analysis found that the association between ACE2 transcription and the number of secondary transmission events differs between patients and healthcare workers. In health care workers Negative Binomial regression estimated that a one unit change in ACE2 transcription decreases the number of secondary cases (B = -0.132 (95%CI: -0.255 to -0.0181) adjusting for RNA viral load. Conversely, in patients a one unit change in ACE2 transcription increases the number of secondary cases (B = 0.187 (95% CI: 0.0101 to 0.370) adjusting for RNA viral load. Sensitivity analysis found no significant relationship between ACE2 and secondary transmission in health care workers and confirmed the positive association among patients. Conclusion: Our study suggests that ACE2 transcription has a positive association with SARS-CoV-2 secondary transmission in admitted inpatients, but not health care workers in concurrent hospital associated outbreaks, and it should be further investigated as a risk-factor for viral transmission.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.20.23287264v1" target="_blank">Nasopharyngeal Angiotensin Converting Enzyme 2 (ACE2) Expression as a Risk-Factor for SARS-CoV-2 Transmission in Concurrent Hospital Associated Outbreaks</a>
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</div></li>
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<li><strong>SARS-CoV-2 infection induces dopaminergic neuronal loss in midbrain organoids during short and prolonged cultures</strong> -
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COVID-19 is mainly associated with respiratory symptoms, although several reports showed that SARS-CoV-2 affects the nervous system. We evaluated the effects of infection in prolonged culture of midbrain organoids, showing that the virus induces changes in gene expression, and fragmentation and loss of dopaminergic neurons. Our findings highlight the direct viral-induced damage to midbrain organoids indicating the relevance of assessing the neurological long-term evolution of COVID-19 patients.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.20.533485v1" target="_blank">SARS-CoV-2 infection induces dopaminergic neuronal loss in midbrain organoids during short and prolonged cultures</a>
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<li><strong>Nanograms of SARS-CoV-2 Spike Protein Delivered by Exosomes Induce Potent Neutralization of Both Delta and Omicron Variants.</strong> -
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Exosomes are emerging as potent and safe delivery carriers for use in vaccinology and therapeutics. A better vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to provide improved, broader, longer lasting neutralization of SARS-CoV-2, a more robust T cell response, enable widespread global usage, and further enhance the safety profile of vaccines given the likelihood of repeated booster vaccinations. Here, we use Capricor’s StealthXTM platform to engineer exosomes to express native SARS-CoV-2 spike Delta variant (STX-S) protein on the surface for the delivery of a protein-based vaccine for immunization against SARS-CoV-2 infection. The STX-S vaccine induced a strong immunization with the production of a potent humoral immune response as demonstrated by high levels of neutralizing antibody not only against the delta SARS-CoV-2 virus but also two Omicron variants (BA.1 and BA.5), providing broader protection than current mRNA vaccines. Additionally, both CD4+ and CD8+ T cell responses were increased significantly after treatment. Quantification of spike protein by ELISA showed that only nanograms of protein were needed to induce a potent immune response. This is a significantly lower dose than traditional recombinant protein vaccines with no adjuvant required, which makes the StealthXTM exosome platform ideal for the development of multivalent vaccines with a better safety profile. Importantly, our exosome platform allows novel proteins, or variants in the case of SARS-CoV-2, to be engineered onto the surface of exosomes in a matter of weeks, comparable with mRNA vaccine technology, but without the cold storage requirements. The ability to utilize exosomes for cellular delivery of proteins, as demonstrated by STX-S, has enormous potential to revolutionize vaccinology by rapidly facilitating antigen presentation at an extremely low dose resulting in a potent, broad antibody response.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.20.533560v1" target="_blank">Nanograms of SARS-CoV-2 Spike Protein Delivered by Exosomes Induce Potent Neutralization of Both Delta and Omicron Variants.</a>
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<li><strong>COVID-19 on mind: Daily worry about the coronavirus is linked to negative affect experienced during mind-wandering and dreaming</strong> -
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Despite a surge of studies on the effects of COVID-19 on our well-being, we know little about how the pandemic is reflected in people’s spontaneous thoughts and experiences, such as mind-wandering (or daydreaming) during wakefulness and dreaming during sleep. We investigated whether and how COVID-19 related general concern, anxiety, and daily worry are associated with the daily fluctuation of the affective quality of mind-wandering and dreaming, and to what extent these associations can be explained by poor sleep quality. We used ecological momentary assessment by asking participants to rate the affect they experienced during mind-wandering and dreaming in daily logs over a two-week period. Our preregistered analyses based on 1755 dream logs from 172 individuals and 1496 mind-wandering logs from 152 individuals showed that, on days when people reported higher levels of negative affect and lower levels of positive affect during mind-wandering, they experienced more worry. Only daily sleep quality was associated with affect experienced during dreaming at the within-person level: on nights with poorer sleep quality people reported experiencing more negative and less positive affect in dreams and were more likely to experience nightmares. However, at the between-person level, individuals who experienced more daily COVID-19 worry during the study period also reported experiencing more negative affect during mind-wandering and during dreaming. As such, the continuity between daily and nightly experiences seems to rely more on stable trait-like individual differences in affective processing.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/bk4tn/" target="_blank">COVID-19 on mind: Daily worry about the coronavirus is linked to negative affect experienced during mind-wandering and dreaming</a>
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<li><strong>Design and implementation of a system for automated monitoring of adherence to evidenced-based clinical guideline recommendations</strong> -
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Background Clinical practice guidelines are systematically developed statements intended to optimize patient care. However, a gap-less implementation of guideline recommendations requires health care personnel not only to be aware of the recommendations and to support their content, but also to recognize every situation in which they are applicable. To not miss situations in which guideline recommendations should be applied, computerized clinical decision support could be given through a system that allows an automated monitoring of adherence to clinical guideline recommendation in individual patients. Objectives (1) To derive the requirements for a system that allows to monitor the adherence to evidence-based clinical guideline recommendations in individual patients, and based on these requirements, (2) to implement a software prototype that integrates clinical guideline recommendations with individual patient data and (3) to demonstrate the prototype9s utility on a COVID-19 intensive care treatment recommendation. Methods We performed a work process analysis with experienced intensive care clinicians to develop a conceptual model of how to support guideline adherence monitoring in clinical routine and identified which steps in the model could be supported electronically. We then identified the core requirements of a software system for supporting recommendation adherence monitoring in a consensus-based requirements analysis within loosely structured focus group work of key stakeholders (clinicians, guideline developers, health data engineers, software developers). Based on these requirements, we implemented a prototype and demonstrated its functionality by integrating clinical data with a treatment recommendation. Results Based on our conceptual flow chart model of recommendation adherence monitoring in clinical routine, we identified four main requirements of a software system for automated support of recommendation adherence monitoring of in-hospital patients: (i) Ability to interpret guideline recommendations9 semantics and logics, (ii) integration of clinical routine data from various underlying data structures, (iii) automatic adoption of new or updated guideline recommendations, and (iv) user interfaces optimized for distinct groups of users. Using a prototype implementation that fulfills these requirements, we demonstrate how such a system could be applied to monitor guideline recommendation adherence over time in clinical patients. Conclusions The four main requirements identified through our model-based analysis represent the most important aspects that need to be considered when developing a clinical decision support system for monitoring the adherence to evidence-based clinical guideline recommendations in individual patients. As each of the requirements corresponds to a different expertise (guideline development, health data engineering, software development, patient treatment), a modularized software architecture separated by area of required expertise seems favorable. Our prototype successfully demonstrates how such a modular architecture can be implemented to allow real-time monitoring of guideline recommendation adherence. This prototype, which we released as open source to invigorate collaboration, could serve as a basis for further development to integrate guideline recommendations with clinical information systems.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.18.22277750v2" target="_blank">Design and implementation of a system for automated monitoring of adherence to evidenced-based clinical guideline recommendations</a>
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<li><strong>Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID</strong> -
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BACKGROUND Mechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 “PASC” or “Long COVID”) remain unclear. This study sought to elucidate mechanisms of cardiopulmonary symptoms and reduced exercise capacity using advanced cardiac testing. METHODS We performed cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring among adults > 1 year after confirmed SARS-CoV-2 infection in Long-Term Impact of Infection with Novel Coronavirus cohort (LIINC; substudy of NCT04362150). Adults who completed a research echocardiogram (at a median 6 months after SARS-CoV-2 infection) without evidence of heart failure or pulmonary hypertension were asked to complete additional cardiopulmonary testing approximately 1 year later. Although participants were recruited as a prospective cohort, to account for selection bias, the primary analyses were as a case-control study comparing those with and without persistent cardiopulmonary symptoms. We also correlated findings with previously measured biomarkers. We used logistic regression and linear regression models to adjust for potential confounders including age, sex, body mass index, time since SARS-CoV-2 infection, and hospitalization for acute SARS-CoV-2 infection, with sensitivity analyses adjusting for medical history. RESULTS Sixty participants (unselected for symptoms, median age 53, 42% female, 87% non-hospitalized) were studied at median 17.6 months following SARS-CoV-2 infection. On maximal CPET, 18/37 (49%) with symptoms had reduced exercise capacity (peak VO2<85% predicted) compared to 3/19 (16%) without symptoms (p=0.02). The adjusted peak VO2 was 5.2 ml/kg/min (95%CI 2.1-8.3; p=0.001) or 16.9% lower actual compared to predicted (95%CI 4.3-29.6; p=0.02) among those with symptoms compared to those without symptoms. Chronotropic incompetence was present among 12/21 (57%) with reduced VO2 including 11/37 (30%) with symptoms and 1/19 (5%) without (p=0.04). Inflammatory markers (hsCRP, IL-6, TNF-α) and SARS-CoV-2 antibody levels measured early in PASC were negatively correlated with peak VO2 more than 1 year later. Late-gadolinium enhancement on CMR and arrhythmias on ambulatory monitoring were not present. CONCLUSIONS We found evidence of objectively reduced exercise capacity among those with cardiopulmonary symptoms more than 1 year following COVID-19, which was associated with elevated inflammatory markers early in PASC. Chronotropic incompetence may explain exercise intolerance among some with cardiopulmonary phenotype Long COVID.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.17.22275235v3" target="_blank">Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID</a>
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<li><strong>The short- and long-term impacts of COVID-19 on household energy consumption in England and Wales</strong> -
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The COVID-19 pandemic changed the way many people lived, worked, and studied around the world, both during and after the lockdowns. Changes to daily routines affected domestic electricity and gas use. While early studies estimated the impact of the first national lockdown, the long-term effects remain under-researched. In this paper we analyse how domestic electricity and gas consumption changed in the two years since the first UK lockdown in terms of both total demand and timing of demand. We develop counterfactual (predictive) models using elastic net regression, neural networks, and extreme gradient boosting and compare observed energy use with predicted use given weather and calendar variables for each household (508 for electricity, 326 for gas). We apply cluster analysis to identify common daily energy demand profiles and observe the changes in the proportions of households in each cluster for 3540 (electricity) and 2850 (gas) households between January 2020 and March 2022. We compare the results for different subsamples, such as those with and without children or working adults, households with different levels of financial wellbeing, and households in different Energy Performance Certificate (EPC) bands. We find that the pandemic increased electricity consumption throughout the two-year period, and increased gas consumption during the winter lockdowns. Demand profiles for weekdays became more similar to those on weekends for households with children or with adults in work. On average electricity consumption was still around 5% higher than predicted at the start of 2022, largely due to increased use in households with children. On average, gas consumption was lower than predicted during winter 2021/22, which may be attributable to rising gas prices.
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🖺 Full Text HTML: <a href="https://osf.io/m5p3b/" target="_blank">The short- and long-term impacts of COVID-19 on household energy consumption in England and Wales</a>
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<li><strong>Troops on the Front Line of a Health Battle: Filipino Nurses’ Lived Experiences in the Pandemic</strong> -
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The deadly pandemic spread due to infections with the Coronavirus (COVID-19). It has a disproportionately large effect on healthcare workers and presents unique challenges for this vital sector of society. As a result, the pandemic has heightened public awareness of the dangers that nurses face around the world. This study aimed at exploring the lived experiences of five purposively selected nurses in a public hospital in the southern Philippines. The phenomenological inquiry brought out themes encompassing (1) putting up with occupational stress, (2) reconfiguring personal and social time, and (3) coping with the situation’s gravity. These themes have been fleshed out to capture deeper meanings in the experiences of nurses during the health crisis in which they are deemed to be crucial front liners. The study concludes that while the nurses’ quality of life has been impacted due to the unprecedented situation, they remain committed to their profession. The study then implies that the government should be more responsive to the needs of the nurses and that support and assistance in their practice of the nursing profession amid the pandemic be provided substantially. Implications for hospital administrators and future researchers are also offered.
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🖺 Full Text HTML: <a href="https://osf.io/q6frb/" target="_blank">Troops on the Front Line of a Health Battle: Filipino Nurses’ Lived Experiences in the Pandemic</a>
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<li><strong>Surveillance of 16 UK native bat species through conservationist networks uncovers coronaviruses with zoonotic potential</strong> -
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There has been limited characterisation of bat-borne coronaviruses in Europe. Here, we screened for coronaviruses 48 faecal samples from 16 of the 17 bat species breeding in the UK and collected through a bat rehabilitation and conservationist network. We recovered nine (two novel) complete genomes across six bat species: four alphacoronaviruses, a MERS-related betacoronavirus, and four closely-related sarbecoviruses. We demonstrate that at least one of these sarbecoviruses can bind and use the human ACE2 receptor for infecting human cells, albeit suboptimally. Additionally, the spike proteins of these sarbecoviruses possess an R-A-K-Q motif, which lies only one nucleotide mutation away from a furin cleavage site (FCS) that enhances infectivity in other coronaviruses, including SARS-CoV-2. However, mutating this motif to an FCS does not enable spike cleavage. Overall, while UK sarbecoviruses would require further molecular adaptations to infect humans, their zoonotic risk is unknown but warrants closer surveillance.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.17.524183v4" target="_blank">Surveillance of 16 UK native bat species through conservationist networks uncovers coronaviruses with zoonotic potential</a>
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<li><strong>Introducing the COVID-19 crisis Special Education Needs Coping Survey</strong> -
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Individuals with special education needs have been particularly affected by the COVID-19 pandemic as they have been shown to be at high risk of losing medical and institutional support at a time when people are being asked to stay isolated, suffering increased anxiety and depression as a consequence. Their families have often found themselves under tremendous pressure to provide support, engendering financial hardship, and physical and emotional strains. In such times, it is vital that international collaborations assess the impact on the individuals and their families, affording the opportunity to make national and international comparisons of how people have coped and what needs to be done to optimize the measures taken by families, associations and governments. This paper introduces one such collaboration.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/rtswa/" target="_blank">Introducing the COVID-19 crisis Special Education Needs Coping Survey</a>
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<li><strong>An interpretable, finite sample valid alternative to Pearson’s X2 for scientific discovery</strong> -
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Contingency tables, data represented as counts matrices, are ubiquitous across quantitative research and data-science applications. Existing statistical tests are insufficient however, as none are simultaneously computationally efficient and statistically valid for a finite number of observations. In this work, motivated by a recent application in reference-genome-free inference (Chaung et al., 2022), we develop OASIS (Optimized Adaptive Statistic for Inferring Structure), a family of statistical tests for contingency tables. OASIS constructs a test-statistic which is linear in the normalized data matrix, providing closed form p-value bounds through classical concentration inequalities. In the process, OASIS provides a decomposition of the table, lending interpretability to its rejection of the null. We derive the asymptotic distribution of the OASIS test statistic, showing that these finite-sample bounds correctly characterize the p-value bound derived up to a variance term. Experiments on genomic sequencing data highlight the power and interpretability of OASIS. The same method based on OASIS significance calls detects SARS-CoV-2 and Mycobacterium Tuberculosis strains de novo, which cannot be achieved with current approaches. We demonstrate in simulations that OASIS is robust to overdispersion, a common feature in genomic data like single cell RNA-sequencing, where under accepted noise models OASIS still provides good control of the false discovery rate, while Pearson’s X2 test consistently rejects the null. Additionally, we show on synthetic data that OASIS is more powerful than Pearson’s X2 test in certain regimes, including for some important two group alternatives, which we corroborate with approximate power calculations.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.16.533008v1" target="_blank">An interpretable, finite sample valid alternative to Pearson’s X2 for scientific discovery</a>
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<li><strong>Defining drivers of under-immunisation and vaccine hesitancy in refugee and migrant populations globally to support strategies to strengthen vaccine uptake for COVID-19: a rapid review</strong> -
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Background Some refugee and migrant populations have been disproportionately impacted by the COVID-19 pandemic, yet evidence suggests lower uptake of COVID-19 vaccines. They are also an under-immunised group for many routine vaccines. We did a rapid review to explore drivers of under-immunisation and vaccine hesitancy among refugee and migrant populations globally to define strategies to strengthen both COVID-19 and routine vaccination uptake. Methods We collected global literature (01/01/2010 - 05/05/2022) pertaining to drivers of under-immunisation and vaccine hesitancy in refugees and migrants, incorporating all vaccines. We searched MEDLINE, Embase, Global Health PsycINFO and the WHO Global Research on COVID-19 database and grey literature. Qualitative data were analysed thematically to identify drivers of under-immunisation and vaccine hesitancy, then categorised using the Increasing Vaccination Model. Results 63 papers were included in this review, reporting data on diverse population groups, including refugees, asylum seekers, labour and undocumented migrants from 22 countries, with six papers reporting on a regional or global scale. Drivers of under-immunisation and vaccine hesitancy pertaining to a wide range of vaccines were covered, including COVID-19 (n=27), HPV (13), measles or MMR (3), influenza (3), tetanus (1), and vaccination in general. We found a range of factors driving under-immunisation and hesitancy in refugee and migrant groups, including unique awareness and access factors that need to be better considered in policy and service delivery. Acceptability of vaccination was often deeply rooted in social and historical context and influenced by personal risk perception. Conclusions These findings hold direct relevance to current efforts to ensure high levels of global immunisation coverage, key to which is to ensure marginalised refugees and migrant populations are included in national vaccination plans of low- middle- and high-income countries. We found a stark lack of research from low- and middle-income and humanitarian contexts on vaccination in mobile groups, a situation that needs to be urgently rectified to ensure high coverage for COVID-19 and routine vaccinations.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.20.23287477v1" target="_blank">Defining drivers of under-immunisation and vaccine hesitancy in refugee and migrant populations globally to support strategies to strengthen vaccine uptake for COVID-19: a rapid review</a>
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<li><strong>Leveraging global genomic sequencing data to estimate local variant dynamics</strong> -
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Accurate, reliable, and timely estimates of pathogen variant risk are essential for informing public health responses. Unprecedented rates of genomic sequencing have generated new insights into variant dynamics. However, estimating the fitness advantage of a novel variant shortly after emergence, or its dynamics more generally in data-sparse settings, remains difficult. This challenge is exacerbated in countries where surveillance is limited or intermittent. To stabilize inference in these data-sparse settings, we develop a hierarchical modeling approach to estimate variant fitness advantage and prevalence by pooling data across geographic regions. We demonstrate our method by reconstructing SARS-CoV-2 BA.5 variant emergence, and assess performance using retrospective, out-of-sample validation. We show that stable and robust estimates can be obtained even when sequencing data are sparse. Finally, we discuss how this method can inform risk assessment of novel variants and provide situational awareness on circulating variants for a range of pathogens and use-cases.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.02.23284123v4" target="_blank">Leveraging global genomic sequencing data to estimate local variant dynamics</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>Clinical Performance Evaluation of the CareSuperb™ COVID-19 Antigen Home Test</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: CareSuperb COVID-19 Antigen Home Test Kit<br/><b>Sponsor</b>: AccessBio, 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>Use of E-health Based Exercise Intervention After COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Exercise training using an e-health tool<br/><b>Sponsors</b>: Norwegian University of Science and Technology; University of Oslo<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>Phase I Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102)</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant variant COVID-19 vaccine(Sf9 cell)<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase II Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant variant COVID-19 vaccine (Sf9 cell); Biological: Recombinant COVID-19 vaccine (CHO cell); Biological: Recombinant COVID-19 vaccine (Sf9 cell)<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Short-term Effects of Transdermal Estradiol on Female COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Hormone Replacement Therapy<br/><b>Interventions</b>: Drug: Climara 0.1Mg/24Hr Transdermal System; Other: Hydrogel patch<br/><b>Sponsors</b>: Istanbul University - Cerrahpasa (IUC); Turkish Menopause and Osteoporosis Society; Karakoy Rotary Club; Rebul Pharmacy<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 Kinesio Tape Versus Diaphragmatic Breathing Exercise In Post COVID-19</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Interventions</b>: Other: Pursed lip breathing; Other: Cognitive Behavior Therapy; Other: Diaphragmatic breathing exercise; Other: Kinesio tape<br/><b>Sponsor</b>: Cairo 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>Effect Of Calcitriol On Neutrophil To Lymphocytes Ratio And High Sensitivity C-Reactive Protein Covid-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Calcitriol; Other: Placebo<br/><b>Sponsor</b>: Universitas Sebelas Maret<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>Clinical Study for the Efficacy and Safety of Ropeginterferon Alfa-2b in Moderate COVID19.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: P1101 (Ropeginterferon alfa-2b); Procedure: SOC<br/><b>Sponsor</b>: National Taiwan University Hospital<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>Teletechnology-assisted Home-based Exercise Program for Severe COVID-19</strong> - <b>Conditions</b>: COVID-19; Telerehabilitation<br/><b>Intervention</b>: Behavioral: Teletechnology-assisted home-based pulmonary rehabilitation<br/><b>Sponsor</b>: National Taiwan University 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>Hydrogen-Oxygen Generator With Nebulizer for Adjuvant Treatment of Novel Coronavirus Disease 2019 (COVID-19)</strong> - <b>Conditions</b>: Covid19; Hydrogen-oxygen Gas; AMS-H-03<br/><b>Interventions</b>: Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03; Device: OLO-1 Medical Molecular Sieve Oxygen Generator<br/><b>Sponsor</b>: Guangzhou Institute of Respiratory Disease<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>Cluster-Randomized Trial of Air Filtration and Ventilation to Reduce Covid19 Spread in Homes</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Device: Filtration Fan; Behavioral: Safe-home pamphlet; Behavioral: Mid-week phone call<br/><b>Sponsor</b>: Stanford 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>The Use of Photobiomodulation in the Treatment of Oral Complaints of Long COVID-19.A Randomized Controlled Trial.</strong> - <b>Conditions</b>: Xerostomia; COVID-19; Long COVID; Persistent COVID-19<br/><b>Interventions</b>: Combination Product: Institutional standard treatment for xerostomia and Long Covid; Radiation: Photobiomodulation Therapy; Radiation: Placebo Photobiomodulation Therapy<br/><b>Sponsor</b>: University of Nove de Julho<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>Zinc Supplementation Impact in Acute COVID-19 Clinical Outcomes</strong> - <b>Conditions</b>: Zinc Deficiency; Sars-CoV-2 Infection<br/><b>Intervention</b>: Dietary Supplement: Zinc Acetate<br/><b>Sponsors</b>: Parc de Salut Mar; Universitat Pompeu Fabra<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>Balneotherapy for Patients With Post-acute Coronavirus Disease (COVID) Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Other: Balneotherapy and aquatic exercises<br/><b>Sponsors</b>: Parc de Salut Mar; Caldes de Montbui’s City Council; Consorcio Centro de Investigación Biomédica en Red (CIBER); European Regional Development Fund<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 Study to Assess the Efficacy of HH-120 Nasal Spray for Prevention of SARS-CoV-2 Infection in Adult Close Contacts of Individuals Infected With SARS-CoV-2</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Drug: HH-120 nasal spray 1; Drug: HH-120 nasal spray 2; Drug: Placebo Comparator 1; Drug: Placebo Comparator 2<br/><b>Sponsor</b>: Beijing Ditan Hospital<br/><b>Completed</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>Dietary fish intake increased the concentration of soluble ACE2 in rats. Can fish consumption reduce the risk of COVID-19 infection through interception of SARS-CoV-2 by soluble ACE2?</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells after binding to the membrane-bound receptor angiotensin-converting enzyme 2 (ACE2), but this may be prevented through interception by soluble ACE2 (sACE2) or by inhibition of the ACE2 receptor, thus obstructing cell entry and replication. The main objective of this study was to investigate if fish intake affected the concentration of sACE2 in rats. The secondary aim was to evaluate the in vitro ACE2 inhibiting…</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>Pseudoknot-targeting Cas13b combats SARS-CoV-2 infection by suppressing viral replication</strong> - CRISPR-Cas13-mediated viral genome targeting is a novel strategy for defending against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Here, we generated mRNA-encoded Cas13b targeting the open reading frame 1b (ORF1b) region to effectively degrade the RNA-dependent RNA polymerase gene. Of the 12 designed CRISPR RNAs (crRNAs), those targeting the pseudoknot site upstream of ORF1b were found to be the most effective in suppressing SARS-CoV-2 propagation. Pseudoknot-targeting…</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>Using data mining techniques deep analysis and theoretical investigation of COVID-19 pandemic</strong> - This study uses K-Means Clustering to analyze Corona-Virus Diseases (Covid-19). Data mining in medicine has generated novel approaches to examine diseases. Coronavirus is difficult to treat because of its intricate structure, shape, and texture. Due to data mining improvements, the K-Means approach has been developed for evaluating covid-19. Observe the outbreak’s evolution, including its peak, and containment measures. A basic K-Means model is used to simulate Coronavirus’s prevalence in Iraq….</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>Ceftazidime exhibits a broad inhibition to the infection of SARS-CoV-2 prototype and Omicron variant in vitro by blocking spike protein-ACE2 interaction</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>FXR inhibition: an innovative prophylactic strategy against SARS-CoV-2 infection</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>New bi-phosphonate derivative: Synthesis, characterization, antioxidant activity in vitro and via cyclic voltammetry mode and evaluation of its inhibition of SARS-CoV-2 main protease</strong> - In this study, we have synthesized a new molecule labeled HBPA. Its molecular structure was determined by spectroscopic methods such as: FT-IR, NMR (¹H, ^(13)C and ^(31)P); our compound is subjected to two antioxidant activities assays: DPPH scavenging and ferric reducing antioxidant power (FRAP); in the results, HBPA was expanded remarkable inhibition when compared especially to standard BHT with values of 14.936±0.808 and 7.1486±0.0645 μg/ml, respectively; in addition to the scavenging test 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>Co-pyrolysis of medical protective clothing and oil palm wastes for biofuel: Experimental, techno-economic, and environmental analyses</strong> - The ongoing global pandemic of COVID-19 has devastatingly influenced the environment, society, and economy around the world. Numerous medical resources are used to inhibit the infectious transmission of the virus, resulting in massive medical waste. This study proposes a sustainable and environment-friendly method to convert hazardous medical waste into valuable fuel products through pyrolysis. Medical protective clothing (MPC), a typical medical waste from COVID-19, was utilized for…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An in-solution snapshot of SARS-COV-2 main protease maturation process and inhibition</strong> - The main protease from SARS-CoV-2 (M^(pro)) is responsible for cleavage of the viral polyprotein. M^(pro) self-processing is called maturation, and it is crucial for enzyme dimerization and activity. Here we use C145S M^(pro) to study the structure and dynamics of N-terminal cleavage in solution. Native mass spectroscopy analysis shows that mixed oligomeric states are composed of cleaved and uncleaved particles, indicating that N-terminal processing is not critical for dimerization. A 3.5 Å…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bioactive Compositions of Cinnamon (<em>Cinnamomum verum</em> J. Presl) Extracts and Their Capacities in Suppressing SARS-CoV-2 Spike Protein Binding to ACE2, Inhibiting ACE2, and Scavenging Free Radicals</strong> - Cinnamon (Cinnamomum verum J. Presl) bark and its extracts are popular ingredients added to food and supplement products. It has various health effects, including potentially reducing the risk of coronavirus disease-2019 (COVID-19). In our study, the bioactives in cinnamon water and ethanol extracts were chemically identified, and their potential in suppressing SARS-CoV-2 spike protein-angiotensin-converting enzyme 2 (ACE2) binding, reducing ACE2 availability, and scavenging free radicals was…</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>Structure-based design of a SARS-CoV-2 Omicron-specific inhibitor</strong> - The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) introduced a relatively large number of mutations, including three mutations in the highly conserved heptad repeat 1 (HR1) region of the spike glycoprotein (S) critical for its membrane fusion activity. We show that one of these mutations, N969K induces a substantial displacement in the structure of the heptad repeat 2 (HR2) backbone in the HR1HR2 postfusion bundle. Due to this mutation, fusion-entry peptide…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Omicron-induced interferon signalling prevents influenza A H1N1 and H5N1 virus infection</strong> - Recent findings in permanent cell lines suggested that SARS-CoV-2 Omicron BA.1 induces a stronger interferon response than Delta. Here, we show that BA.1 and BA.5 but not Delta induce an antiviral state in air-liquid interface (ALI) cultures of primary human bronchial epithelial (HBE) cells and primary human monocytes. Both Omicron subvariants caused the production of biologically active type I (α/β) and III (λ) interferons and protected cells from super-infection with influenza A viruses….</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 pharmacokinetic drug-drug interaction study between rosuvastatin and emvododstat, a potent anti-SARS-CoV-2 (COVID-19) DHODH (dihydroorotate dehydrogenase) inhibitor</strong> - A therapeutic agent that targets both viral replication and the hyper-reactive immune response would offer a highly desirable treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) management. Emvododstat (PTC299) was found to be a potent inhibitor of immunomodulatory and inflammation-related processes by the inhibition of dihydroorotate dehydrogenase (DHODH) to reduce SARS-CoV-2 replication. DHODH is the rate-limiting enzyme of the de novo pyrimidine nucleotide…</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>Innovative, rapid, high-throughput method for drug repurposing in a pandemic-A case study of SARS-CoV-2 and COVID-19</strong> - Several efforts to repurpose drugs for COVID-19 treatment have largely either failed to identify a suitable agent or agents identified did not translate to clinical use. Reasons that have been suggested to explain the failures include use of inappropriate doses, that are not clinically achievable, in the screening experiments, and the use of inappropriate pre-clinical laboratory surrogates to predict efficacy. In this study, we used an innovative algorithm, that incorporates dissemination and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Therapeutic developments for SARS-CoV-2 infection-Molecular mechanisms of action of antivirals and strategies for mitigating resistance in emerging variants in clinical practice</strong> - This article systematically presents the current clinically significant therapeutic developments for the treatment of COVID-19 by providing an in-depth review of molecular mechanisms of action for SARS-CoV-2 antivirals and critically analyzing the potential targets that may allow the selection of resistant viral variants. Two main categories of agents can display antiviral activity: direct-acting antivirals, which act by inhibiting viral enzymes, and host-directed antivirals, which target host…</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>Multiple functions of stress granules in viral infection at a glance</strong> - Stress granules (SGs) are distinct RNA granules induced by various stresses, which are evolutionarily conserved across species. In general, SGs act as a conservative and essential self-protection mechanism during stress responses. Viruses have a long evolutionary history and viral infections can trigger a series of cellular stress responses, which may interact with SG formation. Targeting SGs is believed as one of the critical and conservative measures for viruses to tackle the inhibition of…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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