Regional opening strategies with commuter testing and containment of new SARS-CoV-2 variants in Germany.

BACKGROUND: Despite the vaccination process in Germany, a large share of the population is still susceptible to SARS-CoV-2. In addition, we face the spread of novel variants. Until we overcome the pandemic, reasonable mitigation and opening strategies are crucial to balance public health and economic interests. METHODS: We model the spread of SARS-CoV-2 over the German counties by a graph-SIR-type, metapopulation model with particular focus on commuter testing. We account for political interventions by varying contact reduction values in private and public locations such as homes, schools, workplaces, and other. We consider different levels of lockdown strictness, commuter testing strategies, or the delay of intervention implementation. We conduct numerical simulations to assess the effectiveness of the different intervention strategies after one month. The virus dynamics in the regions (German counties) are initialized randomly with incidences between 75 and 150 weekly new cases per 100,000 inhabitants (red zones) or below (green zones) and consider 25 different initial scenarios of randomly distributed red zones (between 2 and 20% of all counties). To account for uncertainty, we consider an ensemble set of 500 Monte Carlo runs for each scenario. RESULTS: We find that the strength of the lockdown in regions with out of control virus dynamics is most important to avoid the spread into neighboring regions. With very strict lockdowns in red zones, commuter testing rates of twice a week can substantially contribute to the safety of adjacent regions. In contrast, the negative effect of less strict interventions can be overcome by high commuter testing rates. A further key contributor is the potential delay of the intervention implementation. In order to keep the spread of the virus under control, strict regional lockdowns with minimum delay and commuter testing of at least twice a week are advisable. If less strict interventions are in favor, substantially increased testing rates are needed to avoid overall higher infection dynamics. CONCLUSIONS: Our results indicate that local containment of outbreaks and maintenance of low overall incidence is possible even in densely populated and highly connected regions such as Germany or Western Europe. While we demonstrate this on data from Germany, similar patterns of mobility likely exist in many countries and our results are, hence, generalizable to a certain extent.

Assessment of effective mitigation and prediction of the spread of SARS-CoV-2 in Germany using demographic information and spatial resolution.

Non-pharmaceutical interventions (NPIs) are important to mitigate the spread of infectious diseases as long as no vaccination or outstanding medical treatments are available. We assess the effectiveness of the sets of non-pharmaceutical interventions that were in place during the course of the Coronavirus disease 2019 (Covid-19) pandemic in Germany. Our results are based on hybrid models, combining SIR-type models on local scales with spatial resolution. In order to account for the age-dependence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we include realistic prepandemic and recently recorded contact patterns between age groups. The implementation of non-pharmaceutical interventions will occur on changed contact patterns, improved isolation, or reduced infectiousness when, e.g., wearing masks. In order to account for spatial heterogeneity, we use a graph approach and we include high-quality information on commuting activities combined with traveling information from social networks. The remaining uncertainty will be accounted for by a large number of randomized simulation runs. Based on the derived factors for the effectiveness of different non-pharmaceutical interventions over the past months, we provide different forecast scenarios for the upcoming time.

Flow-induced adhesion of shear-activated polymers to a substrate.

Adhesion of polymers and proteins to substrates plays a crucial role in many technological applications and biological processes. A prominent example is the von Willebrand factor (VWF) protein, which is essential in blood clotting as it mediates adhesion of blood platelets to the site of injury at high shear rates. VWF is activated by flow and is able to bind efficiently to damaged vessel walls even under extreme flow-stress conditions; however, its adhesion is reversible when the flow strength is significantly reduced or the flow is ceased. Motivated by the properties and behavior of VWF in flow, we investigate adhesion of shear-activated polymers to a planar wall in flow and whether the adhesion is reversible under flow stasis. The main ingredients of the polymer model are cohesive inter-monomer interactions, a catch bond with the adhesive surface, and the shear activation/deactivation of polymer adhesion correlated with its stretching in flow. The cohesive interactions within the polymer maintain a globular conformation under low shear stresses and allow polymer stretching if a critical shear rate is exceeded, which is directly associated with its activation for adhesion. Our results show that polymer adhesion at high shear rates is significantly stabilized by catch bonds, while at the same time they also permit polymer dissociation from a surface at low or no flow stresses. In addition, the activation/deactivation mechanism for adhesion plays a crucial role in the reversibility of its adhesion. These observations help us better understand the adhesive behavior of VWF in flow and interpret its adhesion malfunctioning in VWF-related diseases.

Margination and stretching of von Willebrand factor in the blood stream enable adhesion.

The protein von Willebrand factor (VWF) is essential in primary hemostasis, as it mediates platelet adhesion to vessel walls. VWF retains its compact (globule-like) shape in equilibrium due to internal molecular associations, but is able to stretch when a high enough shear stress is applied. Even though the shear-flow sensitivity of VWF conformation is well accepted, the behavior of VWF under realistic blood flow conditions remains poorly understood. We perform mesoscopic numerical simulations together with microfluidic experiments in order to characterize VWF behavior in blood flow for a wide range of flow-rate and hematocrit conditions. In particular, our results demonstrate that the compact shape of VWF is important for its migration (or margination) toward vessel walls and that VWF stretches primarily in a near-wall region in blood flow making its adhesion possible. Our results show that VWF is a highly optimized protein in terms of its size and internal associations which are necessary to achieve its vital function. A better understanding of the relevant mechanisms for VWF behavior in microcirculation provides a further step toward the elucidation of the role of mutations in various VWF-related diseases.