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null (Ed.)Abstract Despite the global efforts to mitigate the ongoing COVID-19 pandemic, the disease transmission and the effective controls still remain uncertain as the outcome of the epidemic varies from place to place. In this regard, the province-wise data from Nepal provides a unique opportunity to study the effective control strategies. This is because (a) some provinces of Nepal share an open-border with India, resulting in a significantly high inflow of COVID-19 cases from India; (b) despite the inflow of a considerable number of cases, the local spread was quite controlled until mid-June of 2020, presumably due to control policies implemented; and (c) the relaxation of policies caused a rapid surge of the COVID-19 cases, providing a multi-phasic trend of disease dynamics. In this study, we used this unique data set to explore the inter-provincial disparities of the important indicators, such as epidemic trend, epidemic growth rate, and reproduction numbers. Furthermore, we extended our analysis to identify prevention and control policies that are effective in altering these indicators. Our analysis identified a noticeable inter-province variation in the epidemic trend (3 per day to 104 per day linear increase during third surge period), the median daily growth rate (1 to 4% per day exponential growth), the basic reproduction number (0.71 to 1.21), and the effective reproduction number (maximum values ranging from 1.20 to 2.86). Importantly, results from our modeling show that the type and number of control strategies that are effective in altering the indicators vary among provinces, underscoring the need for province-focused strategies along with the national-level strategy in order to ensure the control of a local spread.more » « less
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null (Ed.)The pre-clinical development of antiviral agents involves experimental trials in animals and ferrets as an animal model for the study of SARS-CoV-2. Here, we used mathematical models and experimental data to characterize the within-host infection dynamics of SARS-CoV-2 in ferrets. We also performed a global sensitivity analysis of model parameters impacting the characteristics of the viral infection. We provide estimates of the viral dynamic parameters in ferrets, such as the infection rate, the virus production rate, the infectious virus proportion, the infected cell death rate, the virus clearance rate, as well as other related characteristics, including the basic reproduction number, pre-peak infectious viral growth rate, post-peak infectious viral decay rate, pre-peak infectious viral doubling time, post-peak infectious virus half-life, and the target cell loss in the respiratory tract. These parameters and indices are not significantly different between animals infected with viral strains isolated from the environment and isolated from human hosts, indicating a potential for transmission from fomites. While the infection period in ferrets is relatively short, the similarity observed between our results and previous results in humans supports that ferrets can be an appropriate animal model for SARS-CoV-2 dynamics-related studies, and our estimates provide helpful information for such studies.more » « less
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