Interactions between humans cause transmission of SARS-CoV-2. We demonstrate that heterogeneity in human-human interactions give rise to non-linear infection networks that gain complexity with time. Consequently, targeted vaccination strategies are challenged as such effects are not accurately captured by epidemiological models assuming homogeneous mixing. With vaccines being prepared for global deployment determining optimality for swiftly reaching population level immunity in heterogeneous local communities world-wide is critical. We introduce a model that predicts the effect of vaccination into an ongoing COVID-19 outbreak using precision simulation of human-human interaction and infection networks. We show that simulations incorporating non-linear network complexity and local heterogeneity can enable governance with performance-quantified vaccination strategies. Vaccinating highly interactive people diminishes the risk for an infection wave, while vaccinating the elderly reduces fatalities at low population level immunity. Interestingly, a combined strategy is not better due to non-linear effects. While risk groups should be vaccinated first to minimize fatalities, significant optimality branching is observed with increasing population level immunity. Importantly, we demonstrate that regardless of immunization strategy non-pharmaceutical interventions are required to prevent ICU overload and breakdown of healthcare systems. The approach, adaptable in real-time and applicable to other viruses, provides a highly valuable platform for the current and future pandemics.

Infectious disease outbreaks challenge societies by creating dynamic stochastic infection networks between human individuals in geospatial and demographical contexts. Minimizing human and socioeconomic costs of SARS-CoV-2 and future global pandemics requires datadriven and context-specific integrative modeling of detection-tracing, healthcare, and nonpharmaceutical interventions for decision-processes and reopening strategies. Traditional population-based epidemiological models cannot simulate temporal infection dynamics for individual human behavior in specific geolocations. We present an integrated geolocalized and demographically referenced spatio-temporal stochastic network-and agent-based model of COVID-19 dynamics for human encounters in real-world communities. Simulating intervention scenarios, we quantify effects of protection and identify the importance of early introduction of test-trace measures. Critically, we observe bimodality in SARS-CoV-2 infection dynamics so that the outcome of reopening can flip between good and poor outcomes stochastically. Furthermore, intervention effectiveness depends on strict execution and temporal control i.e. leaks can prevent successful outcomes. Schools are in many scenarios hubs for transmission, reopening scenarios are impacted by infection chain stochasticity and subsequent outbreaks do not always occur. This generalizable geospatial and individualized methodology is unique in precision and specificity compared to prior COVID-19 models [6,16,17,19] and is applicable to scientifically guided decision processes for communities worldwide. MainAs the SARS-CoV-2 pandemic is spreading around the world it is inflicting multi-dimensional damage to humanity: millions of COVID-19 cases are bringing healthcare systems close to collapse, halting or suppressing global and local economies, and normal human life. In response, countries and communities are scrambling to fight the virus with a series of . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

Interactions between humans cause transmission of SARS-CoV-2. We demonstrate that heterogeneity in human-human interactions give rise to non-linear infection networks that gain complexity with time. Consequently, targeted vaccination strategies are challenged as such effects are not accurately captured by epidemiological models assuming homogeneous mixing. With vaccines being prepared for global deployment determining optimality for swiftly reaching population level immunity in heterogeneous local communities world-wide is critical. We introduce a model that predicts the effect of vaccination into an ongoing COVID-19 outbreak using precision simulation of human-human interaction and infection networks. We show that simulations incorporating non-linear network complexity and local heterogeneity can enable governance with performance-quantified vaccination strategies. Vaccinating highly interactive people diminishes the risk for an infection wave, while vaccinating the elderly reduces fatalities at low population level immunity. Interestingly, a combined strategy is not better due to non-linear effects. While risk groups should be vaccinated first to minimize fatalities, significant optimality branching is observed with increasing population level immunity. Importantly, we demonstrate that regardless of immunization strategy non-pharmaceutical interventions are required to prevent ICU overload and breakdown of healthcare systems. The approach, adaptable in real-time and applicable to other viruses, provides a highly valuable platform for the current and future pandemics.

Reaching population immunity against COVID-19 is proving difficult even in countries with high vaccination levels. Thus, it is critical to identify limits of control and effective measures against future outbreaks. The effects of nonpharmaceutical interventions (NPIs) and vaccination strategies are analyzed with a detailed community-specific agent-based model (ABM). The authors demonstrate that the threshold for population immunity is not a unique number, but depends on the vaccination strategy. Prioritizing highly interactive people diminishes the risk for an infection wave, while prioritizing the elderly minimizes fatalities when vaccinations are low. Control over COVID-19 outbreaks requires adaptive combination of NPIs and targeted vaccination, exemplified for Germany for January-September 2021. Bimodality emerges from the heterogeneity and stochasticity of community-specific human-human interactions and infection networks, which can render the effects of limited NPIs uncertain. The authors' simulation platform can process and analyze dynamic COVID-19 epidemiological situations in diverse communities worldwide to predict pathways to population immunity even with limited vaccination.