Phylogeographic Inference of SARS-CoV-2 Delta Wave in Texas, USA using a Novel Spatial Transmission Count Statistic (preprint)

Viral genomes contain records of geographic movements and cross-scale transmission dynamics. However, the impact of population heterogeneity, particularly among rural and urban areas, on viral spread and epidemic trajectory has been less explored due to limited data availability. Intensive and widespread efforts to collect and sequence SARS-CoV-2 viral samples have enabled the development of comparative genomic approaches to reconstruct spatial transmission history and understand viral transmission across different scales. Large genomic datasets with few mutations present challenges for traditional phylodynamic approaches. To address this issue, we propose a novel spatial transmission count statistic that efficiently summarizes the geographic transmission patterns imprinted on viral phylogenies. Our analysis pipeline reconstructs a time-scaled phylogeny with ancestral trait states and identifies spatial transmission linkages, categorized as imports, local transmission, and exports. These linkages are summarized to represent the epidemic profile of the focal area. We demonstrate the utility of this approach for near real-time outbreak analysis using over 12,000 full genomes and linked epidemiological data to investigate the spread of the SARS-CoV-2 Delta variant in Texas. Our goal is to trace the Delta variants origin, timing and to understand the role of urban and rural areas in the spatial diffusion patterns observed in Texas. Our study shows (1) highly populated urban centers were the main sources of the epidemic in Texas; (2) the outbreaks in urban centers were connected to the global epidemic; and (3) outbreaks in urban centers were locally maintained, while epidemics in rural areas were driven by repeated introductions. Significance StatementWe developed a novel phylogeographic approach that analyzes transmission patterns at low computational cost. This method not only facilitates the inference of spatial scales of transmission but also enables exploration of how specific demographic characteristics influence transmission patterns among heterogenous populations. The rural population in the US, comprising approximately 60 million individuals, has been significantly impacted by COVID-19. Applying our new method, we examined the variations in epidemic patterns between urban centers (e.g., Houston) and rural areas in Texas. We found that urban centers are the primary source for SARS-CoV-2 in rural areas. This analysis lays the groundwork for designing effective public health interventions specifically tailored to the needs of affected areas.

Planning for Emerging Infectious Disease Pandemics

Problem, research strategy, and findingsPlanners have not paid enough attention to managing the risk of emerging infectious diseases (EIDs), of which COVID-19 is the most recent manifestation. Overlooking aggressive policies to manage this risk of zoonotic viruses reassorting between sick animals and humans misses the greatest opportunity for stopping future disease pandemics. In this study we review several disciplines, outline the scant planning literature on EIDs, and identify the increasing calls from virologists and medical professionals to address urbanization as a key EID driver. Using the case of avian influenza outbreaks in Vietnam in 2004 and 2005, we conceptualize a preventive planning approach to managing the risk of zoonotic transmission that results in EID pandemics.Takeaway for practiceWe make several recommendations for planners. Practicing planners should consider how their plans manage the risk of zoonotic disease transmission between animals and humans through land use planning and community planning. Planning education and certification organizations should develop positions regarding the role of planning for EIDs. Food systems planners should consider the importance of livestock practices in food production as a risk factor for EIDs. Diverse research teams should combine geographic scales, data sources, and disciplinary knowledge to examine how an extended series of upstream and downstream events can result in a global pandemic. Such empirical examination can lead to effective planning policies to greatly reduce this risk.

Family Dinners and Family Relationships following the Initial Onset of the COVID-19 Pandemic

In the context of the COVID-19 shutdowns, we explored associations between family dinner and family well-being among 731 adult parents in the United States who currently had at least one child residing in their home. The panel survey was administered during the summer of 2020 (June 18 through July 22). Participants were asked to respond to questions about relational processes before the COVID-19 shutdowns, at the height of the shutdowns, and currently (i.e., at the time of data collection). Results suggest that maintaining regular family meals or increasing the frequency of these meals was associated with increased closeness and more positive perceptions of the impact of the pandemic. Participants' qualitative responses to several open-ended questions are used to provide additional insights and nuance to the quantitative findings.

Changes in Spiritual Practices and Relational Well-Being During the COVID-19 Pandemic

Given disruptions to families' routines and processes wrought by the COVID-19 pandemic, this article explores associations between changes in the frequency of spiritual practices and relational well-being during COVID-19. Using a survey of 1,510 adults in the United States administered during the summer of 2020, we employed a mixed methods approach. Significant associations were found between the frequency of engaging in spiritual practices and relational well-being. Specifically, engaging in spiritual practices was associated with increased emotional closeness and a greater likelihood of reporting a positive lasting effect of the pandemic on family relationships. Our findings suggest that some families and individuals may find that engaging in individual or group spiritual practices, including yoga and meditation, mindfulness, and enjoying nature, fostered resilience and growth during the pandemic.

Changes in Home-Centered Religious Practices and Relational Wellbeing following the Initial Onset of the COVID-19 Pandemic

We explored associations between changes in the frequency of home-centered religious practices and family relational conflict, emotional closeness, and the perceived long-term impact of the COVID-19 pandemic on relationships. The panel survey of 1,510 adult individuals in the United States, was administered during the summer of 2020. Given our interest in understanding changes in religious practices following the COVID-19 related closures of religious institutions, the panel included an intentional oversampling of religious individuals from diverse religious affiliations. We employed a mixed methods approach (integrated quantitative and qualitative measures). Controlling for a large group of demographic variables (e.g., age, gender, race/ethnicity) and other factors (e.g., religiosity, stage of COVID-19 closures), OLS and logistic regressions found some significant associations between retrospectively reported changes in the frequency of religious practices and emotional closeness and perceived lasting impact of the pandemic on family well-being. Qualitative data from a subsample of survey participants (n = 624) suggested that family prayer, scripture study, shared sacred rituals, and home-based worship helped foster positive family interactions.

Discovery of SARS-CoV-2 Mpro peptide inhibitors from modelling substrate and ligand binding.

The main protease (Mpro) of SARS-CoV-2 is central to viral maturation and is a promising drug target, but little is known about structural aspects of how it binds to its 11 natural cleavage sites. We used biophysical and crystallographic data and an array of biomolecular simulation techniques, including automated docking, molecular dynamics (MD) and interactive MD in virtual reality, QM/MM, and linear-scaling DFT, to investigate the molecular features underlying recognition of the natural Mpro substrates. We extensively analysed the subsite interactions of modelled 11-residue cleavage site peptides, crystallographic ligands, and docked COVID Moonshot-designed covalent inhibitors. Our modelling studies reveal remarkable consistency in the hydrogen bonding patterns of the natural Mpro substrates, particularly on the N-terminal side of the scissile bond. They highlight the critical role of interactions beyond the immediate active site in recognition and catalysis, in particular plasticity at the S2 site. Building on our initial Mpro-substrate models, we used predictive saturation variation scanning (PreSaVS) to design peptides with improved affinity. Non-denaturing mass spectrometry and other biophysical analyses confirm these new and effective 'peptibitors' inhibit Mpro competitively. Our combined results provide new insights and highlight opportunities for the development of Mpro inhibitors as anti-COVID-19 drugs.

A landscape planning agenda for global health security: Learning from the history of HIV/AIDS and pandemic influenza.

This paper considers the role of landscape planning and design in the context of a growing need for research and policy recommendations associated with Emerging Infectious Diseases (EIDs), of which COVID-19 is the most recent. Beginning with a definition of EIDs and their origins within the context of landscape planning, the paper then argues that planning and design scholars and practitioners should begin by seeing the importance of a "global urban ecosystem" (GUE) comprised of rapidly transforming metropolitan and regional "patches" connected through "corridors" of relatively unregulated global transportation and mobility networks. It then revisits the history of the two prior global pandemics of HIV/AIDS and pandemic influenza to establish the importance of a landscape planning perspective at the intersection of wildlife, livestock, and globally connected human communities. The essay concludes by arguing that this GUE concept can facilitate creative planning and design by adapting concepts established in other patch and corridor networks like urban transit systems to the ongoing risk of future pandemic EIDs.

Molecular Simulations suggest Vitamins, Retinoids and Steroids as Ligands of the Free Fatty Acid Pocket of the SARS-CoV-2 Spike Protein*.

We investigate binding of linoleate and other potential ligands to the recently discovered fatty acid binding site in the SARS-CoV-2 spike protein, using docking and molecular dynamics simulations. Simulations suggest that linoleate and dexamethasone stabilize the locked spike conformation, thus reducing the opportunity for ACE2 interaction. In contrast, cholesterol may expose the receptor-binding domain by destabilizing the closed structure, preferentially binding to a different site in the hinge region of the open structure. We docked a library of FDA-approved drugs to the fatty acid site using an approach that reproduces the structure of the linoleate complex. Docking identifies steroids (including dexamethasone and vitamin D); retinoids (some known to be active in vitro, and vitamin A); and vitamin K as potential ligands that may stabilize the closed conformation. The SARS-CoV-2 spike fatty acid site may bind a diverse array of ligands, including dietary components, and therefore provides a promising target for therapeutics or prophylaxis.

Planning for Emerging Infectious Disease Pandemics

Problem, research strategy, and findings Takeaway for practice Planners have not paid enough attention to managing the risk of emerging infectious diseases (EIDs), of which COVID-19 is the most recent manifestation. Overlooking aggressive policies to manage this risk of zoonotic viruses reassorting between sick animals and humans misses the greatest opportunity for stopping future disease pandemics. In this study we review several disciplines, outline the scant planning literature on EIDs, and identify the increasing calls from virologists and medical professionals to address urbanization as a key EID driver. Using the case of avian influenza outbreaks in Vietnam in 2004 and 2005, we conceptualize a preventive planning approach to managing the risk of zoonotic transmission that results in EID pandemics.We make several recommendations for planners. Practicing planners should consider how their plans manage the risk of zoonotic disease transmission between animals and humans through land use planning and community planning. Planning education and certification organizations should develop positions regarding the role of planning for EIDs. Food systems planners should consider the importance of livestock practices in food production as a risk factor for EIDs. Diverse research teams should combine geographic scales, data sources, and disciplinary knowledge to examine how an extended series of upstream and downstream events can result in a global pandemic. Such empirical examination can lead to effective planning policies to greatly reduce this risk. [ABSTRACT FROM AUTHOR] Copyright of Journal of the American Planning Association is the property of Routledge and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

COVID-19 in Ghana: Changes and the Way Forward

As a lower-middle income country, Ghana is noted for having a progressive economy, health system, and family trends. However, COVID-19, with it associated restrictions, has brought changes to various aspects of Ghanaians’ lives. In this paper, we review information from government websites, online media websites, social media, academic articles, and anecdotal evidence to track changes brought about by the pandemic. Specifically, we focus on economic well-being, education and schooling, family interaction, mental health and communication in community as well ethnic, cultural, and social class variations. Findings show that the COVID-19 pandemic is changing life for all Ghanaians, notably by reinforcing existing inequalities and highlighting previously known gaps in service, coverage, and access across multiple sectors, including healthcare, business and education. Family patterns are changing for both the nuclear and extended family units. The pandemic has created both challenges and opportunities for parents to engage with their children. Anxiety levels are heightened and psychological services have consequently been made widely available. Education has slowly and unevenly gone virtual. Further, the crisis has generated local innovations to meet the nation’s needs during the pandemic. The findings call for national reforms in the production and distribution of goods and services in all sectors as well as empirical work into the long-term effects of the pandemic on Ghanaians.Alternate abstract: En tant que pays à revenu intermédiaire de la tranche inférieure, le Ghana est réputé pour son économie, son système de santé et ses tendances familiales progressistes. Cependant, COVID-19, avec ses restrictions associées, a apporté des changements à divers aspects de la vie des Ghanéens. Dans cet article, nous examinons les informations provenant des sites Web du gouvernement, des sites Web des médias en ligne, des médias sociaux, des articles universitaires et des preuves anecdotiques pour suivre les changements provoqués par la pandémie. Plus précisément, nous nous concentrons sur le bien-être économique, l'éducation et la scolarité, l'interaction familiale, la santé mentale et la communication au sein de la communauté ainsi que les variations de classe ethnique, culturelle et sociale. Les résultats montrent que la pandémie de COVID-19 change la vie de tous les Ghanéens, notamment en renforçant les inégalités existantes et en mettant en évidence les lacunes précédemment connues en matière de services, de couverture et d'accès dans plusieurs secteurs, notamment les soins de santé, les affaires et l'éducation. Les schémas familiaux évoluent aussi bien pour les unités nucléaires que pour les familles élargies. La pandémie a créé à la fois des défis et des opportunités pour les parents de s'engager avec leurs enfants. Les niveaux d'anxiété augmentent et les services psychologiques sont par conséquent largement diffusés. L'éducation est devenue lentement et inégalement virtuelle. De plus, la crise a généré des innovations locales pour répondre aux besoins du pays pendant la pandémie. Les résultats appellent à des réformes nationales dans la production et la distribution de biens et services dans tous les secteurs ainsi qu'à des travaux empiriques sur les effets à long terme de la pandémie sur les Ghanéens.

Frontispiece: Molecular Simulations suggest Vitamins, Retinoids and Steroids as Ligands of the Free Fatty Acid Pocket of the SARS-CoV-2 Spike Protein

Drug Docking The binding of linoleate and other potential ligands to the recently discovered fatty acid binding site in the SARS-CoV-2 spike protein is investigated by James Spencer, Adrian J. Mulholland et?al. in their Research Article on page?7098.