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 ▲]

Dynamical SPQEIR model assesses the effectiveness of non-pharmaceutical interventions against COVID-19 epidemic outbreaks.

in PloS one (2021), 16(5), 0252019

Against the current COVID-19 pandemic, governments worldwide have devised a variety of non-pharmaceutical interventions to mitigate it. However, it is generally difficult to estimate the joint impact of ... [more ▼]

Against the current COVID-19 pandemic, governments worldwide have devised a variety of non-pharmaceutical interventions to mitigate it. However, it is generally difficult to estimate the joint impact of different control strategies. In this paper, we tackle this question with an extended epidemic SEIR model, informed by a socio-political classification of different interventions. First, we inquire the conceptual effect of mitigation parameters on the infection curve. Then, we illustrate the potential of our model to reproduce and explain empirical data from a number of countries, to perform cross-country comparisons. This gives information on the best synergies of interventions to control epidemic outbreaks while minimising impact on socio-economic needs. For instance, our results suggest that, while rapid and strong lockdown is an effective pandemic mitigation measure, a combination of social distancing and early contact tracing can achieve similar mitigation synergistically, while keeping lower isolation rates. This quantitative understanding can support the establishment of mid- and long-term interventions, to prepare containment strategies against further outbreaks. This paper also provides an online tool that allows researchers and decision makers to interactively simulate diverse scenarios with our model. [less ▲]

SARS-CoV-2 Transmission in Educational Settings During an Early Summer Epidemic Wave in Luxembourg

E-print/Working paper (2020)

Background: The role of schools and children in the transmission of SARS-CoV-2 remains to be determined. Following a first wave in spring and gradual easing of lockdown, Luxembourg experienced an early ... [more ▼]

Background: The role of schools and children in the transmission of SARS-CoV-2 remains to be determined. Following a first wave in spring and gradual easing of lockdown, Luxembourg experienced an early second epidemic wave before the start of summer school holidays on 15th July. This provided the opportunity to study the role of school-age children and school settings in SARS-CoV-2 transmission. More specifically, we compared the incidence in school-age children, teachers and the general working population, and estimated the number of secondary transmissions occurring at schools using contact tracing data. Findings: While SARS-CoV-2 incidence was much higher in adults aged 20 and above than in children aged 0 to 19 during the first wave in spring, no significant difference was found during the second wave in early summer. The incidence during the second wave was similar for pupils, teachers and the general working population. Based on a total of 424 reported confirmed COVID-19 cases in school-age children and teachers, we estimate that 179 index cases caused 49 secondary transmissions in schools. While some small clusters of mainly student-to-student transmission within the same class were identified, we did not observe any large outbreaks with multiple generations of infection. Interpretation: Transmission of SARS-CoV-2 within Luxembourg schools was limited during the early summer epidemic wave in 2020. Precautionary measures including physical distancing as well as easy access to testing, systematic contact tracing appears to have been successful in mitigating transmission within educational settings. Funding Statement: LV is supported by the Luxembourg National Research Fund grant COVID-19/2020- 1/14701707/REBORN, LM is supported by Luxembourg National Research Fund grant COVID19/14863306/PREVID, PW is supported by the European Research Council (ERC-CoG 863664). Declaration of Interests: No competing interests. Ethics Approval Statement: The Health Directorate has the legal permission to process patient confidential information for national surveillance of communicable diseases in general and contact tracing for the COVID-19 pandemic and individual patient consent is not required. [less ▲]

Causal dynamical modelling predicts novel regulatory genes of FOXP3 in human regulatory T cells

E-print/Working paper (2020)

Dynamical Modeling Techniques for Biological Time Series Data

Doctoral thesis (2019)

The present thesis is articulated over two main topics which have in common the modeling of the dynamical properties of complex biological systems from large-scale time-series data. On one hand, this ... [more ▼]

The present thesis is articulated over two main topics which have in common the modeling of the dynamical properties of complex biological systems from large-scale time-series data. On one hand, this thesis analyzes the inverse problem of reconstructing Gene Regulatory Networks (GRN) from gene expression data. This first topic seeks to reverse-engineer the transcriptional regulatory mechanisms involved in few biological systems of interest, vital to understand the specificities of their different responses. In the light of recent mathematical developments, a novel, flexible and interpretable modeling strategy is proposed to reconstruct the dynamical dependencies between genes from short-time series data. In addition, experimental trade-offs and optimal modeling strategies are investigated for given data availability. Consistent literature on these topics was previously surprisingly lacking. The proposed methodology is applied to the study of circadian rhythms, which consists in complex GRN driving most of daily biological activity across many species. On the other hand, this manuscript covers the characterization of dynamically differentiable brain states in Zebrafish in the context of epilepsy and epileptogenesis. Zebrafish larvae represent a valuable animal model for the study of epilepsy due to both their genetic and dynamical resemblance with humans. The fundamental premise of this research is the early apparition of subtle functional changes preceding the clinical symptoms of seizures. More generally, this idea, based on bifurcation theory, can be described by a progressive loss of resilience of the brain and ultimately, its transition from a healthy state to another characterizing the disease. First, the morphological signatures of seizures generated by distinct pathological mechanisms are investigated. For this purpose, a range of mathematical biomarkers that characterizes relevant dynamical aspects of the neurophysiological signals are considered. Such mathematical markers are later used to address the subtle manifestations of early epileptogenic activity. Finally, the feasibility of a probabilistic prediction model that indicates the susceptibility of seizure emergence over time is investigated. The existence of alternative stable system states and their sudden and dramatic changes have notably been observed in a wide range of complex systems such as in ecosystems, climate or financial markets. [less ▲]

Dynamical differential expression (DyDE) reveals the period control mechanisms of the Arabidopsis circadian oscillator

in PLoS Computational Biology (2019)

The circadian oscillator, an internal time-keeping device found in most organisms, enables timely regulation of daily biological activities by maintaining synchrony with the external environment. The ... [more ▼]

The circadian oscillator, an internal time-keeping device found in most organisms, enables timely regulation of daily biological activities by maintaining synchrony with the external environment. The mechanistic basis underlying the adjustment of circadian rhythms to changing external conditions, however, has yet to be clearly elucidated. We explored the mechanism of action of nicotinamide in Arabidopsis thaliana, a metabolite that lengthens the period of circadian rhythms, to understand the regulation of circadian period. To identify the key mechanisms involved in the circadian response to nicotinamide, we developed a systematic and practical modeling framework based on the identification and comparison of gene regulatory dynamics. Our mathematical predictions, confirmed by experimentation, identified key transcriptional regulatory mechanisms of circadian period and uncovered the role of blue light in the response of the circadian oscillator to nicotinamide. We suggest that our methodology could be adapted to predict mechanisms of drug action in complex biological systems. [less ▲]

Reconstruction of Gene Regulatory Networks using an Error Filtering Learning Scheme

Scientific Conference (2017)

One of the fundamental and most challenging problems in system biology is the reconstruction of gene regulatory networks from input-output data based on non-linear differential equations. This paper ... [more ▼]

One of the fundamental and most challenging problems in system biology is the reconstruction of gene regulatory networks from input-output data based on non-linear differential equations. This paper presents an approach to estimate the unknown nonlinearities and to identify the true network that generated the data, based on an error filtering learning scheme and a Lyapunov synthesis method. Unknown nonlinearities are modelled by networks using radial basis functions and model validation is performed by taking advantage of the so-called persistency of excitation of input signals, a condition that is shown to play a significant role in the problem of uncovering the true network structure. The proposed methodology and the theoretical results are validated through an illustrative example. [less ▲]

Continuous Glucose Monitoring: Using CGM to Guide Insulin Therapy Virtual Trials Results

in IFAC-PapersOnLine (2015)

Continuous glucose monitoring (CGM) devices can measure blood glucose levels through interstitial measurements almost continuously (1-5min sampling period). However, they are not as accurate as glucose ... [more ▼]

Continuous glucose monitoring (CGM) devices can measure blood glucose levels through interstitial measurements almost continuously (1-5min sampling period). However, they are not as accurate as glucose readings from blood measurements. The relation between tissue and blood glucose is dynamic and the sensor signal can degrade over time. In addition, CGM readings contains high frequency noise and can drift between measurements. However, maintaining continuous glucose monitoring has the potential to improve the level of glycemic control achieved and reduce nurse workload. For this purpose, a simple model was designed and tested to see the effect of inherent CGM error on the insulin therapy protocol, STAR (Stochastic TARgeted). An error model was generated from 9 patients that had one Guardian Real-Time CGM device (Medtronic Minimed, Northridge, CA, USA) inserted into their abdomen as part of an observation trial assesing the accuracy of CGM measurements compared to a blood gas analyser and glucometer readings. A resulting error model was then used to simulate the outcomes if the STAR protocol was guided by CGM values on 183 virtual patients. CGM alarms for hyper- and hypo-glycaemic region were included to improve patient safety acting as 'guardrails'. The STAR CGM protocol gave good performance and reduced workload by ~50%, reducing the number of measurements per day per patient from 13 to 7. The number of hypoglycaemic events increased compared to the current STAR from 0.03% <2.2mmol/L to 0.32%. However, in comparison to other published protocols it is still a very low level of hypoglycaemia and less than clinically acceptable value of 5% <4.0mmol/L. More importantly this study shows great promise for the future of CGM and their use in clinic. With the a newer generation of sensors, specifically designed for the ICU, promising less noise and drift suggesting that a reduced nurse workload without compromising safety or performance is with in reach. [less ▲]