Supporting COVID-19 policy-making with a predictive epidemiological multi-model warning system.

BACKGROUND: In response to the SARS-CoV-2 pandemic, the Austrian governmental crisis unit commissioned a forecast consortium with regularly projections of case numbers and demand for hospital beds. The goal was to assess how likely Austrian ICUs would become overburdened with COVID-19 patients in the upcoming weeks. METHODS: We consolidated the output of three epidemiological models (ranging from agent-based micro simulation to parsimonious compartmental models) and published weekly short-term forecasts for the number of confirmed cases as well as estimates and upper bounds for the required hospital beds. RESULTS: We report on three key contributions by which our forecasting and reporting system has helped shaping Austria's policy to navigate the crisis, namely (i) when and where case numbers and bed occupancy are expected to peak during multiple waves, (ii) whether to ease or strengthen non-pharmaceutical intervention in response to changing incidences, and (iii) how to provide hospital managers guidance to plan health-care capacities. CONCLUSIONS: Complex mathematical epidemiological models play an important role in guiding governmental responses during pandemic crises, in particular when they are used as a monitoring system to detect epidemiological change points.

During the SARS-CoV-2 pandemic, health authorities make decisions on how and when to implement interventions such as social distancing to avoid overburdening hospitals and other parts of the healthcare system. We combined three mathematical models developed to predict the expected number of confirmed SARS-CoV-2 cases and hospitalizations over the next two weeks. This provides decision-makers and the general public with a combined forecast that is usually more accurate than any of the individual models. Our forecasting system has been used in Austria to decide when to strengthen or ease response measures.

An iterative algorithm for optimizing COVID-19 vaccination strategies considering unknown supply.

BACKGROUND AND OBJECTIVE: The distribution of the newly developed vaccines presents a great challenge in the ongoing SARS-CoV-2 pandemic. Policy makers must decide which subgroups should be vaccinated first to minimize the negative consequences of the pandemic. These decisions must be made upfront and under uncertainty regarding the amount of vaccine doses available at a given time. The objective of the present work was to develop an iterative optimization algorithm, which provides a prioritization order of predefined subgroups. The results of this algorithm should be optimal but also robust with respect to potentially limited vaccine supply. METHODS: We present an optimization meta-heuristic which can be used in a classic simulation-optimization setting with a simulation model in a feedback loop. The meta-heuristic can be applied in combination with any epidemiological simulation model capable of depicting the effects of vaccine distribution to the modeled population, accepts a vaccine prioritization plan in a certain notation as input, and generates decision making relevant variables such as COVID-19 caused deaths or hospitalizations as output. We finally demonstrate the mechanics of the algorithm presenting the results of a case study performed with an epidemiological agent-based model. RESULTS: We show that the developed method generates a highly robust vaccination prioritization plan which is proven to fulfill an elegant supremacy criterion: the plan is equally optimal for any quantity of vaccine doses available. The algorithm was tested on a case study in the Austrian context and it generated a vaccination plan prioritization favoring individuals age 65+, followed by vulnerable groups, to minimize COVID-19 related burden. DISCUSSION: The results of the case study coincide with the international policy recommendations which strengthen the applicability of the approach. We conclude that the path-dependent optimum optimum provided by the algorithm is well suited for real world applications, in which decision makers need to develop strategies upfront under high levels of uncertainty.

Model based estimation of the SARS-CoV-2 immunization level in austria and consequences for herd immunity effects.

Several systemic factors indicate that worldwide herd immunity against COVID-19 will probably not be achieved in 2021. On the one hand, vaccination programs are limited by availability of doses and on the other hand, the number of people already infected is still too low to have a disease preventing impact and new emerging variants of the virus seem to partially neglect developed antibodies from previous infections. Nevertheless, by February 2021 after one year of observing high numbers of reported COVID-19 cases in most European countries, we might expect that the immunization level should have an impact on the spread of SARS-CoV-2. Here we present an approach for estimating the immunization of the Austrian population and discuss potential consequences on herd immunity effects. To estimate immunization we use a calibrated agent-based simulation model that reproduces the actual COVID-19 pandemic in Austria. From the resulting synthetic individual-based data we can extract the number of immunized persons. We then extrapolate the progression of the epidemic by varying the obtained level of immunization in simulations of an hypothetical uncontrolled epidemic wave indicating potential effects on the effective reproduction number. We compared our theoretical findings with results derived from a classic differential equation SIR-model. As of February 2021, [Formula: see text] of the Austrian population has been affected by a SARS-CoV-2 infection which causes a [Formula: see text] reduction of the effective reproduction number and a [Formula: see text] reduction of the prevalence peak compared to a fully susceptible population. This estimation is now recomputed on a regular basis to publish model based analysis of immunization level in Austria also including the fast growing effects of vaccination programs. This provides substantial information for decision makers to evaluate the necessity of non pharmaceutical intervention measures based on the estimated impact of natural and vaccinated immunization.

Time Dynamics of the Spread of Virus Mutants with Increased Infectiousness in Austria.

In spring 2021, it became eminent that the emergence of higher infectious virus mutants of SARS-CoV-2 is an unpredictable and omnipresent threat for fighting the pandemic and has wide-ranging implications on containment policies and herd immunity goals. To quantify the risk related to a more infectious virus variant, extensive surveillance and proper data analysis are required. Key observable of the analysis is the excess infectiousness defined as the quotient between the effective reproduction rate of the new and the previous variants. A proper estimate of this parameter allows forecasts for the epidemic situation after the new variant has taken over and enables estimates by how much the new variant will increase the herd immunity threshold. Here, we present and analyse methods to estimate this crucial parameter based on surveillance data. We specifically focus on the time dynamics of the ratio of mutant infections among the new confirmed cases and discuss, how the excess infectiousness can be estimated based on surveillance data for this ratio. We apply a modified susceptible-infectious-recovered approach and derive formulas which can be used to estimate this parameter. We will provide adaptations of the formulas which are able to cope with imported cases and different generation-times of mutant and previous variants and furthermore fit the formulas to surveillance data from Austria. We conclude that the derived methods are well capable of estimating the excess infectiousness, even in early phases of the replacement process. Yet, a high ratio of imported cases from regions with higher variant prevalence may cause a major overestimation of the excess infectiousness, if not considered. Consequently, the analysis of Austrian data allowed a proper estimate for the Alpha variant, but results for the Delta variant are inconclusive.

Evaluation of Contact-Tracing Policies against the Spread of SARS-CoV-2 in Austria: An Agent-Based Simulation.

BACKGROUND: Many countries have already gone through several infection waves and mostly managed to successfully stop the exponential spread of SARS-CoV-2 through bundles of restrictive measures. Still, the danger of further waves of infections is omnipresent, and it is apparent that every containment policy must be carefully evaluated and possibly replaced by a different, less restrictive policy before it can be lifted. Tracing of contacts and consequential breaking of infection chains is a promising strategy to help contain the disease, although its precise impact on the epidemic is unknown. OBJECTIVE: In this work, we aim to quantify the impact of tracing on the containment of the disease and investigate the dynamic effects involved. DESIGN: We developed an agent-based model that validly depicts the spread of the disease and allows for exploratory analysis of containment policies. We applied this model to quantify the impact of different approaches of contact tracing in Austria to derive general conclusions on contract tracing. RESULTS: The study displays that strict tracing complements other intervention strategies. For the containment of the disease, the number of secondary infections must be reduced by about 75%. Implementing the proposed tracing strategy supplements measures worth about 5%. Evaluation of the number of preventively quarantined persons shows that household quarantine is the most effective in terms of avoided cases per quarantined person. LIMITATIONS: The results are limited by the validity of the modeling assumptions, model parameter estimates, and the quality of the parametrization data. CONCLUSIONS: The study shows that tracing is indeed an efficient measure to keep case numbers low but comes at a high price if the disease is not well contained. Therefore, contact tracing must be executed strictly, and adherence within the population must be held up to prevent uncontrolled outbreaks of the disease.

Targeted COVID-19 Vaccination (TAV-COVID) Considering Limited Vaccination Capacities-An Agent-Based Modeling Evaluation.

(1) Background: The Austrian supply of COVID-19 vaccine is limited for now. We aim to provide evidence-based guidance to the authorities in order to minimize COVID-19-related hospitalizations and deaths in Austria. (2) Methods: We used a dynamic agent-based population model to compare different vaccination strategies targeted to the elderly (65 ≥ years), middle aged (45-64 years), younger (15-44 years), vulnerable (risk of severe disease due to comorbidities), and healthcare workers (HCW). First, outcomes were optimized for an initially available vaccine batch for 200,000 individuals. Second, stepwise optimization was performed deriving a prioritization sequence for 2.45 million individuals, maximizing the reduction in total hospitalizations and deaths compared to no vaccination. We considered sterilizing and non-sterilizing immunity, assuming a 70% effectiveness. (3) Results: Maximum reduction of hospitalizations and deaths was achieved by starting vaccination with the elderly and vulnerable followed by middle-aged, HCW, and younger individuals. Optimizations for vaccinating 2.45 million individuals yielded the same prioritization and avoided approximately one third of deaths and hospitalizations. Starting vaccination with HCW leads to slightly smaller reductions but maximizes occupational safety. (4) Conclusion: To minimize COVID-19-related hospitalizations and deaths, our study shows that elderly and vulnerable persons should be prioritized for vaccination until further vaccines are available.

Reproduction of patterns in melanocytic proliferations by agent-based simulation and geometric modeling.

Spatio-temporal patterns of melanocytic proliferations observed in vivo are important for diagnosis but the mechanisms that produce them are poorly understood. Here we present an agent-based model for simulating the emergence of the main biologic patterns found in melanocytic proliferations. Our model portrays the extracellular matrix of the dermo-epidermal junction as a two-dimensional manifold and we simulate cellular migration in terms of geometric translations driven by adhesive, repulsive and random forces. Abstracted cellular functions and melanocyte-matrix interactions are modeled as stochastic events. For identification and validation we use visual renderings of simulated cell populations in a horizontal perspective that reproduce growth patterns observed in vivo by sequential dermatoscopy and corresponding vertical views that reproduce the arrangement of melanocytes observed in histopathologic sections. Our results show that a balanced interplay of proliferation and migration produces the typical reticular pattern of nevi, whereas the globular pattern involves additional cellular mechanisms. We further demonstrate that slight variations in the three basic cellular properties proliferation, migration, and adhesion are sufficient to produce a large variety of morphological appearances of nevi. We anticipate our model to be a starting point for the reproduction of more complex scenarios that will help to establish functional connections between abstracted microscopic behavior and macroscopic patterns in all types of melanocytic proliferations including melanoma.

Health Care Atlases: Informing the General Public About the Situation of the Austrian Health Care System.

There is a great number of complex data concerning the Austrian Health Care System. The goal was to process this data and present it to the general public on an easily accessible information platform. The platform focuses on data about the burden of disease of the Austrian Population, the available medical care and the services provided by the physicians. Due to the vast differences in the underlying source data, the methods used for the data acquisition range from statistical linkage over web scraping to aggregating data on the reimbursed services. The results are published on a website and are mainly displayed with interactive graphics. Overall, these dynamic and interactive websites provide a good overview of the situation of the Austrian Health Care System and presents the information in an intuitive and comprehensible manner. Furthermore, the information given in the atlases can contribute to the health care planning in order to identify distinctive service provision in Austria.