How have researchers defined institutions, politics, organizations and governance in research related to epidemic and pandemic response? A scoping review to map current concepts.

In recent years, the literature on public health interventions and health outcomes in the context of epidemic and pandemic response has grown immensely. However, relatively few of these studies have situated their findings within the institutional, political, organizational and governmental (IPOG) context in which interventions and outcomes exist. This conceptual mapping scoping study synthesized the published literature on the impact of IPOG factors on epidemic and pandemic response and critically examined definitions and uses of the terms IPOG in this literature. This research involved a comprehensive search of four databases across the social, health and biomedical sciences as well as multi-level eligibility screening conducted by two independent reviewers. Data on the temporal, geographic and topical range of studies were extracted, then descriptive statistics were calculated to summarize these data. Hybrid inductive and deductive qualitative analysis of the full-text articles was conducted to critically analyse the definitions and uses of these terms in the literature. The searches retrieved 4918 distinct articles; 65 met the inclusion criteria and were thus reviewed. These articles were published from 2004 to 2022, were mostly written about COVID-19 (61.5%) and most frequently engaged with the concept of governance (36.9%) in relation to epidemic and pandemic response. Emergent themes related to the variable use of the investigated terms, the significant increase in relevant literature published amidst the COVID-19 pandemic, as well as a lack of consistent definitions used across all four terms: institutions, politics, organizations and governance. This study revealed opportunities for health systems researchers to further engage in interdisciplinary work with fields such as law and political science, to become more forthright in defining factors that shape responses to epidemics and pandemics and to develop greater consistency in using these IPOG terms in order to lessen confusion among a rapidly growing body of literature.

Investigating the influence of institutions, politics, organizations, and governance on the COVID-19 response in British Columbia, Canada: a jurisdictional case study protocol.

BACKGROUND: Research on public health responses to COVID-19 globally has largely focused on understanding the virus' epidemiology, identifying interventions to curb transmission, and assessing the impact of interventions on outcomes. Only recently have studies begun to situate their findings within the institutional, political, or organizational contexts of jurisdictions. Within British Columbia (BC), Canada, the COVID-19 response in early 2020 was deemed highly coordinated and effective overall; however, little is understood as to how these upstream factors influenced policy decisions. METHODS: Using a conceptual framework we developed, we are conducting a multidisciplinary jurisdictional case study to explore the influence of institutional (I), political (P), organizational (O), and governance (G) factors on BC's COVID-19 public health response in 2020-2021. A document review (e.g. policy documents, media reports) is being used to (1) characterize relevant institutional and political factors in BC, (2) identify key policy decisions in BC's epidemic progression, (3) create an organizational map of BC's public health system structure, and (4) identify key informants for interviews. Quantitative data (e.g. COVID-19 case, hospitalization, death counts) from publicly accessible sources will be used to construct BC's epidemic curve. Key informant interviews (n = 15-20) will explore governance processes in the COVID-19 response and triangulate data from prior procedures. Qualitative data will be analysed using a hybrid deductive-inductive coding approach and framework analysis. By integrating all of the data streams, our aim is to explore decision-making processes, identify how IPOG factors influenced policy decisions, and underscore implications for decision-making in public health crises in the BC context and elsewhere. Knowledge users within the jurisdiction will be consulted to construct recommendations for future planning and preparedness. DISCUSSION: As the COVID-19 pandemic evolves, governments have initiated retrospective examinations of their policies to identify lessons learned. Our conceptual framework articulates how interrelations between IPOG contextual factors might be applied to such analysis. Through this jurisdictional case study, we aim to contribute findings to strengthen governmental responses and improve preparedness for future health crises. This protocol can be adapted to and applied in other jurisdictions, across subnational jurisdictions, and internationally.

Computationally Designed ACE2 Decoy Receptor Binds SARS-CoV-2 Spike (S) Protein with Tight Nanomolar Affinity.

Even with the availability of vaccines, therapeutic options for COVID-19 still remain highly desirable, especially in hospitalized patients with moderate or severe disease. Soluble ACE2 (sACE2) is a promising therapeutic candidate that neutralizes SARS CoV-2 infection by acting as a decoy. Using computational mutagenesis, we designed a number of sACE2 derivatives carrying three to four mutations. The top-predicted sACE2 decoy based on the in silico mutagenesis scan was subjected to molecular dynamics and free-energy calculations for further validation. After illuminating the mechanism of increased binding for our designed sACE2 derivative, the design was verified experimentally by flow cytometry and BLI-binding experiments. The computationally designed sACE2 decoy (ACE2-FFWF) bound the receptor-binding domain of SARS-CoV-2 tightly with low nanomolar affinity and ninefold affinity enhancement over the wild type. Furthermore, cell surface expression was slightly greater than wild-type ACE2, suggesting that the design is well-folded and stable. Having an arsenal of high-affinity sACE2 derivatives will help to buffer against the emergence of SARS CoV-2 variants. Here, we show that computational methods have become sufficiently accurate for the design of therapeutics for current and future viral pandemics.

Modeling the effect of exposure notification and non-pharmaceutical interventions on COVID-19 transmission in Washington state.

Contact tracing is increasingly used to combat COVID-19, and digital implementations are now being deployed, many based on Apple and Google's Exposure Notification System. These systems utilize non-traditional smartphone-based technology, presenting challenges in understanding possible outcomes. In this work, we create individual-based models of three Washington state counties to explore how digital exposure notifications combined with other non-pharmaceutical interventions influence COVID-19 disease spread under various adoption, compliance, and mobility scenarios. In a model with 15% participation, we found that exposure notification could reduce infections and deaths by approximately 8% and 6% and could effectively complement traditional contact tracing. We believe this can provide health authorities in Washington state and beyond with guidance on how exposure notification can complement traditional interventions to suppress the spread of COVID-19.

Gibberellin driven growth in elf3 mutants requires PIF4 and PIF5.

The regulatory connections between the circadian clock and hormone signaling are essential to understand, as these two regulatory processes work together to time growth processes relative to predictable environmental events. Gibberellins (GAs) are phytohormones that control many growth processes throughout all stages of the plant life cycle, including germination and flowering. An increasing number of examples demonstrate that the circadian clock directly influences GA biosynthesis and signaling. EARLY FLOWERING 3 (ELF3) participates in a tripartite transcriptional complex known as the Evening Complex (EC). In this capacity, ELF3 is fundamental to core circadian clock activity, as well as time-of-day specific regulation of genes directly responsible for growth control, namely the PHYTOCHROME INTERACTING FACTOR 4 (PIF4) and PIF5 genes. Here we show that the GA biosynthesis inhibitor paclobutrazol substantially reduces the long hypocotyl and petiole phenotypes of Arabidopsis elf3 mutants. In addition, loss of ELF3 activity causes upregulation of the key GA biosynthesis genes GA20ox1 and GA20ox2. Moreover, GA20ox1 and GA20ox2 expression depends strongly on the redundant activities of PIF4 and PIF5. These findings indicate that the defining growth phenotypes of elf3 mutants arise from altered GA biosynthesis due to misregulation of PIF4 and PIF5. These observations agree with recent work linking increased GA production with the elongated growth phenotypes of the barley elf3 mutant. Thus, the role of the EC in regulation of GA biosynthesis and signaling in eudicots is shared with monocots and, therefore, is a highly conserved mechanism for growth control.