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4. Inferring age-specific differences in susceptibility to and infectiousness upon SARS-CoV-2 infection based on Belgian social contact data

Author

Franco, Nicolas, Coletti, Pietro, Willem, Lander, Angeli, Leonardo, Lajot, Adrien, Abrams, Steven, Beutels, Philippe, Faes, Christel, and Hens, Niel

Subjects
Quantitative Biology - Populations and Evolution, Statistics - Computation, 92-08, 92C60, 92D30
Abstract

Several important aspects related to SARS-CoV-2 transmission are not well known due to a lack of appropriate data. However, mathematical and computational tools can be used to extract part of this information from the available data, like some hidden age-related characteristics. In this paper, we present a method to investigate age-specific differences in transmission parameters related to susceptibility to and infectiousness upon contracting SARS-CoV-2 infection. More specifically, we use panel-based social contact data from diary-based surveys conducted in Belgium combined with the next generation principle to infer the relative incidence and we compare this to real-life incidence data. Comparing these two allows for the estimation of age-specific transmission parameters. Our analysis implies the susceptibility in children to be around half of the susceptibility in adults, and even lower for very young children (preschooler). However, the probability of adults and the elderly to contract the infection is decreasing throughout the vaccination campaign, thereby modifying the picture over time., Comment: Revised version, 17 pages, supplementary material 15 pages

Published
2021
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5. A look into the future of the COVID-19 pandemic in Europe: an expert consultation

Author

Iftekhar, Emil Nafis, Priesemann, Viola, Balling, Rudi, Bauer, Simon, Beutels, Philippe, Valdez, André Calero, Cuschieri, Sarah, Czypionka, Thomas, Dumpis, Uga, Glaab, Enrico, Grill, Eva, Hanson, Claudia, Hotulainen, Pirta, Klimek, Peter, Kretzschmar, Mirjam, Krüger, Tyll, Krutzinna, Jenny, Low, Nicola, Machado, Helena, Martins, Carlos, McKee, Martin, Mohr, Sebastian Bernd, Nassehi, Armin, Perc, Matjaž, Petelos, Elena, Pickersgill, Martyn, Prainsack, Barbara, Rocklöv, Joacim, Schernhammer, Eva, Staines, Anthony, Szczurek, Ewa, Tsiodras, Sotirios, Van Gucht, Steven, and Willeit, Peter

Subjects
Quantitative Biology - Other Quantitative Biology
Abstract

How will the coronavirus disease 2019 (COVID-19) pandemic develop in the coming months and years? Based on an expert survey, we examine key aspects that are likely to influence COVID-19 in Europe. The future challenges and developments will strongly depend on the progress of national and global vaccination programs, the emergence and spread of variants of concern, and public responses to nonpharmaceutical interventions (NPIs). In the short term, many people are still unvaccinated, VOCs continue to emerge and spread, and mobility and population mixing is expected to increase over the summer. Therefore, policies that lift restrictions too much and too early risk another damaging wave. This challenge remains despite the reduced opportunities for transmission due to vaccination progress and reduced indoor mixing in the summer. In autumn 2021, increased indoor activity might accelerate the spread again, but a necessary reintroduction of NPIs might be too slow. The incidence may strongly rise again, possibly filling intensive care units, if vaccination levels are not high enough. A moderate, adaptive level of NPIs will thus remain necessary. These epidemiological aspects are put into perspective with the economic, social, and health-related consequences and thereby provide a holistic perspective on the future of COVID-19., Comment: Manuscript is accepted by The Lancet Regional Health - Europe as a Viewpoint article. Supplementary material can be accessed here: https://owncloud.gwdg.de/index.php/f/1439962756

Published
2021
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6. Cost-effectiveness of adding oseltamivir to primary care for influenza-like-illness: economic evaluation alongside the randomised controlled ALIC4E trial in 15 European countries

Author

Li, Xiao, Bilcke, Joke, van der Velden, Alike W., Bruyndonckx, Robin, Coenen, Samuel, Bongard, Emily, de Paor, Muirrean, Chlabicz, Slawomir, Godycki-Cwirko, Maciek, Francis, Nick, Aabenhus, Rune, Bucher, Heiner C., Colliers, Annelies, De Sutter, An, Garcia-Sangenis, Ana, Glinz, Dominik, Harbin, Nicolay J., Kosiek, Katarzyna, Lindbæk, Morten, Lionis, Christos, Llor, Carl, Mikó-Pauer, Réka, Radzeviciene Jurgute, Ruta, Seifert, Bohumil, Sundvall, Pär-Daniel, Touboul Lundgren, Pia, Tsakountakis, Nikolaos, Verheij, Theo J., Goossens, Herman, Butler, Christopher C., and Beutels, Philippe

Published
2023
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23. Belgian population norms for the EQ-5D-5L, 2018

Author

Van Wilder, Lisa, Charafeddine, Rana, Beutels, Philippe, Bruyndonckx, Robin, Cleemput, Irina, Demarest, Stefaan, De Smedt, Delphine, Hens, Niel, Scohy, Aline, Speybroeck, Niko, Van der Heyden, Johan, Yokota, Renata T. C., Van Oyen, Herman, Bilcke, Joke, and Devleesschauwer, Brecht

Published
2022
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24. Direct and Indirect Costs of Influenza-Like Illness Treated with and Without Oseltamivir in 15 European Countries: A Descriptive Analysis Alongside the Randomised Controlled ALIC4E Trial

Author

Li, Xiao, Bilcke, Joke, van der Velden, Alike W., Bongard, Emily, Bruyndonckx, Robin, Sundvall, Pär-Daniel, Harbin, Nicolay J., Coenen, Samuel, Francis, Nick, Bruno, Pascale, Garcia-Sangenis, Ana, Glinz, Dominik, Kosiek, Katarzyna, Mikó-Pauer, Réka, Radzeviciene Jurgute, Ruta, Seifert, Bohumil, Tsakountakis, Nikolaos, Aabenhus, Rune, Butler, Christopher C., and Beutels, Philippe

Published
2021
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25. Chronic disease patients have fewer social contacts: A pilot survey with implications for transmission dynamics.

Author

Vanderlocht, J., Møgelmose, S., Van Kerckhove, K., Beutels, P., and Hens, N.

Subjects
CHRONIC diseases, SOCIAL contact, COVID-19 pandemic, SOCIOECONOMICS, MATHEMATICAL models
Abstract

Non-communicable diseases (NCD) are the most important cause of death in the world. The socio-economic costs associated with NCDs makes it imperative to prevent and control them in the 21st century. The severe toll that the COVID-19 pandemic has taken worldwide is an unfortunate illustration of our limited insight into the infectious risk for the global population. Co-incidence between NCD and infection offers an underexplored opportunity to design preventive policies. In a pilot survey, we observed that the NCD population displays a substantial reduction in their social contacting behavior as compared to the general population. This indicates that existing mathematical models based on contact surveys in the general population are not applicable to the NCD population and that the risk of acquiring an infection following a contact is probably underestimated. Our demonstration of reduced social mixing in several chronic conditions, raises the question to what extent the social mixing is influenced by the burden of disease. We advocate the design of disease-specific contact surveys to address how the burden of disease associates with social contact behavior and the risk of infection. The SARS-CoV-2 pandemic offers an unprecedented opportunity to gain insight into the importance of infection in the NCD population and to find ways to improve healthcare procedures. [ABSTRACT FROM AUTHOR]

Published
2024
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30. SOCRATES-CoMix: a platform for timely and open-source contact mixing data during and in between COVID-19 surges and interventions in over 20 European countries

Author

Verelst, Frederik, Hermans, Lisa, Vercruysse, Sarah, Gimma, Amy, Coletti, Pietro, Backer, Jantien A., Wong, Kerry L. M., Wambua, James, van Zandvoort, Kevin, Willem, Lander, Bogaardt, Laurens, Faes, Christel, Jarvis, Christopher I., Wallinga, Jacco, Edmunds, W. John, Beutels, Philippe, and Hens, Niel

Published
2021
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32. Data Mining for Longitudinal Data under Multicollinearity and Time Dependence using Penalized Generalized Estimating Equations

Author

Blommaert, Adriaan, Hens, Niel, and Beutels, Philippe

Subjects
Statistics - Methodology, 62
Abstract

Penalized generalized estimating equations with Elastic Net or L2-Smoothly Clipped Absolute Deviation penalization are proposed to simultaneously select the most important variables and estimate their effects for longitudinal Gaussian data when multicollinearity is present. The method is able to consistently select and estimate the main effects even when strong correlations are present. In addition, the potential pitfall of time-dependent covariates is clarified. Both asymptotic theory and simulation results reveal the effectiveness of penalization as a data mining tool for longitudinal data, especially when a large number of variables is present. The method is illustrated by mining for the main determinants of life expectancy in Europe.

Published
2012

33. Estimating infectious disease parameters from data on social contacts and serological status

Author

Goeyvaerts, Nele, Hens, Niel, Ogunjimi, Benson, Aerts, Marc, Shkedy, Ziv, Van Damme, Pierre, and Beutels, Philippe

Subjects
Statistics - Applications
Abstract

In dynamic models of infectious disease transmission, typically various mixing patterns are imposed on the so-called Who-Acquires-Infection-From-Whom matrix (WAIFW). These imposed mixing patterns are based on prior knowledge of age-related social mixing behavior rather than observations. Alternatively, one can assume that transmission rates for infections transmitted predominantly through non-sexual social contacts, are proportional to rates of conversational contact which can be estimated from a contact survey. In general, however, contacts reported in social contact surveys are proxies of those events by which transmission may occur and there may exist age-specific characteristics related to susceptibility and infectiousness which are not captured by the contact rates. Therefore, in this paper, transmission is modeled as the product of two age-specific variables: the age-specific contact rate and an age-specific proportionality factor, which entails an improvement of fit for the seroprevalence of the varicella-zoster virus (VZV) in Belgium. Furthermore, we address the impact on the estimation of the basic reproduction number, using non-parametric bootstrapping to account for different sources of variability and using multi-model inference to deal with model selection uncertainty. The proposed method makes it possible to obtain important information on transmission dynamics that cannot be inferred from approaches traditionally applied hitherto., Comment: 25 pages, 6 figures

Published
2009

46. Increased herpes zoster risk associated with poor HLA-A immediate early 62 protein (IE62) affinity

Author

Meysman, Pieter, De Neuter, Nicolas, Bartholomeus, Esther, Elias, George, Van den Bergh, Johan, Emonds, Marie-Paule, Haasnoot, Geert W., Heynderickx, Steven, Wens, Johan, Michels, Nele R., Lambert, Julien, Lion, Eva, Claas, Frans H. J., Goossens, Herman, Smits, Evelien, Van Damme, Pierre, Van Tendeloo, Viggo, Beutels, Philippe, Suls, Arvid, Mortier, Geert, Laukens, Kris, and Ogunjimi, Benson

Published
2018
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48. Modeling antibody dynamics following herpes zoster indicates that higher varicella-zoster virus viremia generates more VZV-specific antibodies

Author

Besbassi, H, Garcia-Fogeda, I, Quinlivan, M, Breuer, Judy, ABRAMS, Steven, HENS, Niel, OGUNJIMI, Benson, Beutels, P, Besbassi, H, Garcia-Fogeda, I, Quinlivan, M, Breuer, Judy, ABRAMS, Steven, HENS, Niel, OGUNJIMI, Benson, and Beutels, P

Subjects
antibody levels, ordinary differential equations, Immunology, mathematical modeling, Immunology and Allergy, herpes zoster, Human medicine, varicella zoster virus, nonlinear mixed-effects models
Abstract

IntroductionStudying antibody dynamics following re-exposure to infection and/or vaccination is crucial for a better understanding of fundamental immunological processes, vaccine development, and health policy research. MethodsWe adopted a nonlinear mixed modeling approach based on ordinary differential equations (ODE) to characterize varicella-zoster virus specific antibody dynamics during and after clinical herpes zoster. Our ODEs models convert underlying immunological processes into mathematical formulations, allowing for testable data analysis. In order to cope with inter- and intra-individual variability, mixed models include population-averaged parameters (fixed effects) and individual-specific parameters (random effects). We explored the use of various ODE-based nonlinear mixed models to describe longitudinally collected markers of immunological response in 61 herpes zoster patients. ResultsStarting from a general formulation of such models, we study different plausible processes underlying observed antibody titer concentrations over time, including various individual-specific parameters. Among the converged models, the best fitting and most parsimonious model implies that once Varicella-zoster virus (VZV) reactivation is clinically apparent (i.e., Herpes-zoster (HZ) can be diagnosed), short-living and long-living antibody secreting cells (SASC and LASC, respectively) will not expand anymore. Additionally, we investigated the relationship between age and viral load on SASC using a covariate model to gain a deeper understanding of the population's characteristics. ConclusionThe results of this study provide crucial and unique insights that can aid in improving our understanding of VZV antibody dynamics and in making more accurate projections regarding the potential impact of vaccines. Funding BO acknowledges funding received from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement 851752-CELLULOEPI) and Research Foundation Flanders (FWO) (grant agreement 1861219N). NH and IGF acknowledge support from the EBOVAC3 project which has received funding from the IMI2 Joint Undertaking under grant agreement No 800176 (IMI-EU). Acknowledgments We thank Nina Keersmaekers for her contribution in the early stages of this work. Also, we acknowledge that the resources and services used in this work were provided by the VSC (Flemish Supercomputer Center), funded by the Research Foundation - Flanders (FWO) and the Flemish Government.

Published
2023
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50. Exploratory Analysis of the Economically Justifiable Price of a Hypothetical RSV Vaccine for Older Adults in the Netherlands and the United Kingdom

Author

Zeevat, F, Luttjeboer, J, Paulissen, J H J, van der Schans, J, Beutels, P, Boersma, C, Postma, M J, Nair, Harish, Campbell, Harry, Openshaw, Peter, Beutels, Philippe, Bont, Louis, Pollard, Andrew, Molero, Eva, Martinon-Torres, Federico, Heikkinen, Terho, Meijer, Adam, Kølsen Fischer, Thea, van den Berge, Maarten, Giaquinto, Carlo, Kieffer, Alexia, Demont, Clarisse, Gallichan, Scott, Dormitzer, Philip, Leach, Amanda, Dillon, Laura, Aerssens, Jeroen, Rosen, Brian, RESCEU Investigators, Value, Affordability and Sustainability (VALUE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Microbes in Health and Disease (MHD)

Subjects
Rsv vaccine, business.industry, Cost effectiveness, Incidence (epidemiology), MEDLINE, The Netherlands, Exploratory analysis, United Kingdom, Vaccination, Infectious Diseases, Elderly, Older adults, Preventive intervention, Immunology and Allergy, Medicine, Cost-effectiveness, Human medicine, Respiratory Syncytial Virus, business, Biology, health care economics and organizations, RSV Vaccines, Demography
Abstract

Background In older adults, the burden of respiratory syncytial virus (RSV) resembles that of influenza and may even be considered worse due to the lack of preventive interventions. This study was performed to identify the available literature on RSV infection in older adults, and to provide updated exploratory results of the cost-effectiveness of a hypothetical RSV vaccine in the Netherlands and the United Kingdom. Methods A literature search was performed in Medline and EMBASE on 11 November 2019, which served as input for a static decision-tree model that was used to estimate the EJP, for an RSV vaccine applying different willingness-to-pay (WTP) thresholds. WTP thresholds applied were €20 000 and €50 000 per quality-adjusted life-year for the Netherlands, and £20 000 and £30 000 per quality-adjusted life-year for the United Kingdom. Analyses were—in line with country-specific guidelines—conducted from a societal perspective for the Netherlands and a third-party payer perspective for the United Kingdom. The robustness of the cost-effectiveness results was tested in sensitivity analysis. Results After screening the literature, 3 studies for the Netherlands and 6 for the United Kingdom remained to populate the country-specific models. In the base case analysis for the Netherlands (mean RSV incidence, 3.32%), justifiable vaccine prices of €16.38 and €50.03 were found, based on applying the lower and higher WTP thresholds, respectively. Similarly, for the United Kingdom (mean incidence, 7.13%), vaccine prices of £72.29 and £109.74 were found, respectively. Conclusion RSV vaccination may well be cost-effective in both the Netherlands and the United Kingdom, depending on the exact RSV incidence, vaccine effectiveness and price. However, sensitivity analysis showed that the results were robust based on varying the different parameter estimates and assumptions. With RSV vaccines reaching the final stages of development, a strong need exists for cost-effectiveness studies to understand economically justifiable pricing of the vaccine.

Published
2022

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