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.

Viral variant-resolved wastewater surveillance of SARS-CoV-2 at national scale.

SARS-CoV-2 surveillance by wastewater-based epidemiology is poised to provide a complementary approach to sequencing individual cases. However, robust quantification of variants and de novo detection of emerging variants remains challenging for existing strategies. We deep sequenced 3,413 wastewater samples representing 94 municipal catchments, covering >59% of the population of Austria, from December 2020 to February 2022. Our system of variant quantification in sewage pipeline designed for robustness (termed VaQuERo) enabled us to deduce the spatiotemporal abundance of predefined variants from complex wastewater samples. These results were validated against epidemiological records of >311,000 individual cases. Furthermore, we describe elevated viral genetic diversity during the Delta variant period, provide a framework to predict emerging variants and measure the reproductive advantage of variants of concern by calculating variant-specific reproduction numbers from wastewater. Together, this study demonstrates the power of national-scale WBE to support public health and promises particular value for countries without extensive individual monitoring.

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.

Meteorological factors and non-pharmaceutical interventions explain local differences in the spread of SARS-CoV-2 in Austria.

The drivers behind regional differences of SARS-CoV-2 spread on finer spatio-temporal scales are yet to be fully understood. Here we develop a data-driven modelling approach based on an age-structured compartmental model that compares 116 Austrian regions to a suitably chosen control set of regions to explain variations in local transmission rates through a combination of meteorological factors, non-pharmaceutical interventions and mobility. We find that more than 60% of the observed regional variations can be explained by these factors. Decreasing temperature and humidity, increasing cloudiness, precipitation and the absence of mitigation measures for public events are the strongest drivers for increased virus transmission, leading in combination to a doubling of the transmission rates compared to regions with more favourable weather. We conjecture that regions with little mitigation measures for large events that experience shifts toward unfavourable weather conditions are particularly predisposed as nucleation points for the next seasonal SARS-CoV-2 waves.

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.

Contact Tracing for Disease Containment: a Network-Based Analysis.

Since the outbreak of the COVID-19 pandemic in spring 2020, the concept of test, trace, and isolate (TTI) was used as a non-pharmaceutical intervention against further spreading of the disease. Hereby, recent contact partners of newly confirmed SARS-CoV-2 infected persons were identified and isolated along with the originally detected case to avoid potential secondary infections. While the policy is, given the compliance of the traced persons, generally deemed efficient, not much is known about network-specific impact factors. In this work, we aim to evaluate the effectiveness of the TTI strategy when used (1) for diseases with different infectiousness levels and (2) on different contact networks. For the prior, we vary the infection probability per contact, for the latter, we analyse different clustering coefficients. Our goal is to test the validity of two hypotheses: First, we expect the policy to be more efficient if the infectiousness of the disease is small, since the time delay for isolating persons is crucial. Second, due to the implications of the friendship paradox, we expect the policy to be more effective if the clustering coefficient of the underlying contact network is high. We make use of an agent-based network model consisting of three intertwined model parts: an epidemiological SEIR model, a quarantine model and a contact-tracing model. To test the hypotheses, the disease parameters and the clustering coefficient of the underlying contact network are varied. The simulation results show that, indeed, tracing seems to have a slightly larger containment impact for networks with higher clustering, in particular for fast-spreading diseases. Yet, the effects are small compared to the impact of the infectiousness of the disease. Therefore, we find a significant decrease of the policy effectiveness the higher the transmission probability. The latter implies that the containment impact of tracing and isolating contacts becomes more efficient, if supported by additional measures that limit the infection probability or if applied in periods with low negative seasonality effects.

How an election can be safely planned and conducted during a pandemic: Decision support based on a discrete event model.

In 2020, the ongoing COVID-19 pandemic caused major limitations for any aspect of social life and in specific for all events that require a gathering of people. While most events of this kind can be postponed or cancelled, democratic elections are key elements of any democratic regime and should be upheld if at all possible. Consequently, proper planning is required to establish the highest possible level of safety to both voters and scrutineers. In this paper, we present the novel and innovative way how the municipal council and district council elections in Vienna were planned and conducted using an discrete event simulation model. Key target of this process was to avoid queues in front of polling stations to reduce the risk of related infection clusters. In cooperation with a hygiene expert, we defined necessary precautions that should be met during the election in order to avoid the spread of COVID-19. In a next step, a simulation model was established and parametrized and validated using data from previous elections. Furthermore, the planned conditions were simulated to see whether excessive queues in front of any polling stations could form, as these could on the one hand act as an infection herd, and on the other hand, turn voters away. Our simulation identified some polling stations where long queues could emerge. However, splitting up these electoral branches resulted in a smooth election across all of Vienna. Looking back, the election did not lead to a significant increase of COVID-19 incidences. Therefore, it can be concluded that careful planning led to a safe election, despite the pandemic.

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.