Model-based assessment of COVID-19 epidemic dynamics by wastewater analysis

in Science of the Total Environment (2022), 827

Continuous surveillance of COVID-19 diffusion remains crucial to control its diffusion and to anticipate infection waves. Detecting viral RNA load in wastewater samples has been suggested as an effective ... [more ▼]

Continuous surveillance of COVID-19 diffusion remains crucial to control its diffusion and to anticipate infection waves. Detecting viral RNA load in wastewater samples has been suggested as an effective approach for epidemic monitoring and the development of an effective warning system. However, its quantitative link to the epidemic status and the stages of outbreak is still elusive. Modelling is thus crucial to address these challenges. In this study, we present a novel mechanistic model-based approach to reconstruct the complete epidemic dynamics from SARS-CoV-2 viral load in wastewater. Our approach integrates noisy wastewater data and daily case numbers into a dynamical epidemiological model. As demonstrated for various regions and sampling protocols, it quantifies the case numbers, provides epidemic indicators and accurately infers future epidemic trends. Following its quantitative analysis, we also provide recommendations for wastewater data standards and for their use as warning indicators against new infection waves. In situations of reduced testing capacity, our modelling approach can enhance the surveillance of wastewater for early epidemic prediction and robust and cost-effective real-time monitoring of local COVID-19 dynamics. [less ▲]

Modelling COVID-19 dynamics and potential for herd immunity by vaccination in Austria, Luxembourg and Sweden

in Journal of Theoretical Biology (2021)

Against the COVID-19 pandemic, non-pharmaceutical interventions have been widely applied and vaccinations have taken off. The upcoming question is how the interplay between vaccinations and social ... [more ▼]

Against the COVID-19 pandemic, non-pharmaceutical interventions have been widely applied and vaccinations have taken off. The upcoming question is how the interplay between vaccinations and social measures will shape infections and hospitalizations. Hence, we extend the Susceptible-Exposed-Infectious-Removed (SEIR) model including these elements. We calibrate it to data of Luxembourg, Austria and Sweden until 15 December 2020. Sweden results having the highest fraction of undetected, Luxembourg of infected and all three being far from herd immunity in December. We quantify the level of social interaction, showing that a level around 1/3 of before the pandemic was still required in December to keep the effective reproduction number Refft below 1, for all three countries. Aiming to vaccinate the whole population within 1 year at constant rate would require on average 1,700 fully vaccinated people/day in Luxembourg, 24,000 in Austria and 28,000 in Sweden, and could lead to herd immunity only by mid summer. Herd immunity might not be reached in 2021 if too slow vaccines rollout speeds are employed. The model thus estimates which vaccination rates are too low to allow reaching herd immunity in 2021, depending on social interactions. Vaccination will considerably, but not immediately, help to curb the infection; thus limiting social interactions remains crucial for the months to come. [less ▲]

SARS-CoV-2 transmission risk from asymptomatic carriers: Results from a mass screening programme in Luxembourg

in The Lancet Regional Health. Europe (2021), 4

Background To accompany the lifting of COVID-19 lockdown measures, Luxembourg implemented a mass screening (MS) programme. The first phase coincided with an early summer epidemic wave in 2020. Methods rRT ... [more ▼]

Background To accompany the lifting of COVID-19 lockdown measures, Luxembourg implemented a mass screening (MS) programme. The first phase coincided with an early summer epidemic wave in 2020. Methods rRT-PCR-based screening for SARS-CoV-2 was performed by pooling of samples. The infrastructure allowed the testing of the entire resident and cross-border worker populations. The strategy relied on social connectivity within different activity sectors. Invitation frequencies were tactically increased in sectors and regions with higher prevalence. The results were analysed alongside contact tracing data. Findings The voluntary programme covered 49 of the resident and 22 of the cross-border worker populations. It identified 850 index cases with an additional 249 cases from contact tracing. Over-representation was observed in the services, hospitality and construction sectors alongside regional differences. Asymptomatic cases had a significant but lower secondary attack rate when compared to symptomatic individuals. Based on simulations using an agent-based SEIR model, the total number of expected cases would have been 42·9 (90 CI [-0·3, 96·7]) higher without MS. Mandatory participation would have resulted in a further difference of 39·7 [19·6, 59·2]. Interpretation Strategic and tactical MS allows the suppression of epidemic dynamics. Asymptomatic carriers represent a significant risk for transmission. Containment of future outbreaks will depend on early testing in sectors and regions. Higher participation rates must be assured through targeted incentivisation and recurrent invitation. Funding This project was funded by the Luxembourg Ministries of Higher Education and Research, and Health. [less ▲]

Assessing suppression strategies against epidemicoutbreaks like COVID-19: the SPQEIR model

E-print/Working paper (2020)

The current COVID-19 outbreak represents a most serious challenge for societies worldwide. It isendangering the health of millions of people, and resulting in severe socioeconomic challenges dueto lock ... [more ▼]

The current COVID-19 outbreak represents a most serious challenge for societies worldwide. It isendangering the health of millions of people, and resulting in severe socioeconomic challenges dueto lock-down measures. Governments worldwide aim to devise exit strategies to revive the economywhile keeping the pandemic under control. The problem is that the effects of distinct measures arenot well quantified. This paper compares several suppression approaches and potential exit strategiesusing a new extended epidemic SEIR model. It concludes that while rapid and strong lock-down isan effective pandemic suppression measure, a combination of other strategies such as social distanc-ing, active protection and removal can achieve similar suppression synergistically. This quantitativeunderstanding will support the establishment of mid- and long-term interventions. Finally, the paperprovides an online tool that allows researchers and decision makers to interactively simulate diversescenarios with our model. [less ▲]

A multifactorial evaluation framework for gene regulatory network reconstruction

in Foundations of Systems Biology in Engineering (2019)

In the past years, many computational methods have been developed to infer the structure of gene regulatory networks from time series data. However, the applicability and accuracy presumptions of such ... [more ▼]

In the past years, many computational methods have been developed to infer the structure of gene regulatory networks from time series data. However, the applicability and accuracy presumptions of such algorithms remain unclear due to experimental heterogeneity. This paper assesses the performance of recent and successful network inference strategies under a novel, multifactorial evaluation framework in order to highlight pragmatic tradeoffs in experimental design. The effects of data quantity and systems perturbations are addressed, thereby formulating guidelines for efficient resource management. Realistic data were generated from six widely used benchmark models of rhythmic and nonrhythmic gene regulatory systems with random perturbations mimicking the effect of gene knock-out or chemical treatments. Then, time series data of increasing lengths were provided to five state-of-the-art network inference algorithms representing distinctive mathematical paradigms. The performances of such network reconstruction methodologies are uncovered under various experimental conditions. We report that the algorithms do not benefit equally from data increments. Furthermore, at least for the studied rhythmic system, it is more profitable for network inference strategies to be run on long time series rather than short time series with multiple perturbations. By contrast, for the non-rhythmic systems, increasing the number of perturbation experiments yielded better results than increasing the sampling frequency. We expect that future benchmark and algorithm design would integrate such multifactorial considerations to promote their widespread and conscientious usage. [less ▲]

Spatial discretization error in Kalman filtering for discrete-time infinite dimensional systems

in IMA Journal of Mathematical Control and Information (2018), 35(suppl_1), 51-72

We derive a reduced-order state estimator for discrete-time infinite dimensional linear systems with finite dimensional Gaussian input and output noise. This state estimator is the optimal one-step ... [more ▼]

We derive a reduced-order state estimator for discrete-time infinite dimensional linear systems with finite dimensional Gaussian input and output noise. This state estimator is the optimal one-step estimate that takes values in a fixed finite dimensional subspace of the system’s state space — consider, for example, a Finite Element space. The structure of the obtained state estimator is like the Kalman filter, but with an additional optimal embedding operator mapping from the reduced space to the original state space. We derive a Riccati difference equation for the error covariance and use sensitivity analysis to obtain a bound for the error of the state estimate due to the state space discretization. [less ▲]

Bayesian variable selection in linear dynamical systems

E-print/Working paper (2018)

We develop a method for reconstructing regulatory interconnection networks between variables evolving according to a linear dynamical system. The work is motivated by the problem of gene regulatory ... [more ▼]

We develop a method for reconstructing regulatory interconnection networks between variables evolving according to a linear dynamical system. The work is motivated by the problem of gene regulatory network inference, that is, finding causal effects between genes from gene expression time series data. In biological applications, the typical problem is that the sampling frequency is low, and consequentially the system identification problem is ill-posed. The low sampling frequency also makes it impossible to estimate derivatives directly from the data. We take a Bayesian approach to the problem, as it offers a natural way to incorporate prior information to deal with the ill-posedness, through the introduction of sparsity promoting prior for the underlying dynamics matrix. It also provides a framework for modelling both the process and measurement noises. We develop Markov Chain Monte Carlo samplers for the discrete-valued zero-structure of the dynamics matrix, and for the continuous-time trajectory of the system. [less ▲]

Convergence of discrete time Kalman filter estimate to continuous time estimate

in International Journal of Control (2016), 89(4), 668-679

Acoustic wave guides as infinite-dimensional dynamical systems

in ESAIM: Control, Optimisation and Calculus of Variations (2015), 21(2), 324-347

Interaction of vocal fold and vocal tract oscillations

in Proceedings of the 24th Nordic Seminar on Computational Mechanics (2011)

We study the mechanical feedback coupling between the human vocal folds and vocal tract (VT) by simulating fundamental frequency glides over the lowest VT resonance. In the classical source–filter theory ... [more ▼]

We study the mechanical feedback coupling between the human vocal folds and vocal tract (VT) by simulating fundamental frequency glides over the lowest VT resonance. In the classical source–filter theory of speech production, the vocal folds produce a signal which is filtered by the resonator, vocal tract without any feedback. We have developed a computational model of the vocal folds and the VT that also includes a counter pressure from the VT to the vocal folds. This coupling gives rise to new computational observations (such as modal locking) that can be established experimentally. [less ▲]