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Spatially distributed infection increases viral load in a computational model of SARS-CoV-2 lung infectionSmith, Amber M (Ed.)A key question in SARS-CoV-2 infection is why viral loads and patient outcomes vary dramatically across individuals. Because spatial-temporal dynamics of viral spread and immune response are challenging to study in vivo, we developed Spatial Immune Model of Coronavirus (SIMCoV), a scalable computational model that simulates hundreds of millions of lung cells, including respiratory epithelial cells and T cells. SIMCoV replicates viral growth dynamics observed in patients and shows how spatially dispersed infections can lead to increased viral loads. The model also shows how the timing and strength of the T cell response can affect viral persistence, oscillations, and control. By incorporating spatial interactions, SIMCoV provides a parsimonious explanation for the dramatically different viral load trajectories among patients by varying only the number of initial sites of infection and the magnitude and timing of the T cell immune response. When the branching airway structure of the lung is explicitly represented, we find that virus spreads faster than in a 2D layer of epithelial cells, but much more slowly than in an undifferentiated 3D grid or in a well-mixed differential equation model. These results illustrate how realistic, spatially explicit computational models can improve understanding of within-host dynamics of SARS-CoV-2 infection.
Perception is central to the survival of an individual for many reasons, especially as it affects the ability to gather resources. Consequently, costs associated with perception are partially shaped by resource availability. Understanding the interplay of environmental factors (such as the density and distribution of resources) with species-specific factors (such as growth rate, mutation, and metabolic costs) allows the exploration of possible trajectories by which perception may evolve. Here, we used an agent-based foraging model with a context-dependent movement strategy in which each agent switches between undirected and directed movement based on its perception of resources. This switching behavior is central to our goal of exploring how environmental and species-specific factors determine the evolution and maintenance of perception in an ecological system. We observed a non-linear response in the evolved perceptual ranges as a function of parameters in our model. Overall, we identified two groups of parameters, one of which promotes evolution of perception and another group that restricts it. We found that resource density, basal energy cost, perceptual cost and mutation rate were the best predictors of the resultant perceptual range distribution, but detailed exploration indicated that individual parameters affect different parts of the distribution in different ways.