Structural differences in mixing behavior informing the role of asymptomatic infection and testing symptom heritability.

Most infectious disease data is obtained from disease surveillance which is based on observations of symptomatic cases only. However, many infectious diseases are transmitted before the onset of symptoms or without developing symptoms at all throughout the entire disease course, referred to as asymptomatic transmission. Fraser and colleagues [1] showed that this type of transmission plays a key role in assessing the feasibility of intervention measures in controlling an epidemic outbreak. To account for asymptomatic transmission in epidemic models, methods often rely on assumptions that cannot be verified given the data at hand. The present study aims at assessing the contribution of social contact data from asymptomatic and symptomatic individuals in quantifying the contribution of (a)symptomatic infections. We use a mathematical model based on ordinary differential equations (ODE) and a likelihood-based approach followed by Markov Chain Monte Carlo (MCMC) to estimate the model parameters and their uncertainty. Incidence data on influenza-like illness in the initial phase of the 2009 A/H1N1pdm epidemic is used to illustrate that it is possible to estimate either the proportion of asymptomatic infections or the relative infectiousness of symptomatic versus asymptomatic infectives. Further, we introduce a model in which the chance of developing symptoms depends on the disease state of the person that transmitted the infection. In conclusion, incorporating social contact data from both asymptomatic and symptomatic individuals allows inferring on parameters associated with asymptomatic infection based on disease data from symptomatic cases only

Modelling Forced Vital Capacity in Idiopathic Pulmonary Fibrosis: Optimising Trial Design

Introduction: Forced vital capacity is the only registrational endpoint in idiopathic pulmonary fibrosis clinical trials. As most new treatments will be administered on top of standard of care, estimating treatment response will become more challenging. We developed a simulation model to quantify variability associated with forced vital capacity decline. Methods: The model is based on publicly available clinical trial summary and home spirometry data. A single, illustrative trial setting is reported. Model assumptions are 400 subjects randomised 1:1 to investigational drug or placebo over 52 weeks, 50% of each group receiving standard of care (all-comer population), and a 90-mL treatment difference in annual forced vital capacity decline. Longitudinal profiles were simulated and the impact of varying clinical scenarios evaluated. Results: Power to detect a significant treatment differe

Household members do not contact each other at random: implications for infectious disease modelling

Airborne infectious diseases such as influenza are primarily transmitted from human to human by means of social contacts, and thus easily spread within households. Epidemic models, used to gain insight into infectious disease spread and control, typically rely on the assumption of random mixing within households. Until now, there has been no direct empirical evidence to support this assumption. Here, we present the first social contact survey specifically designed to study contact networks within households. The survey was conducted in Belgium (Flanders and Brussels) from 2010 to 2011. We analysed data from 318 households totalling 1266 individuals with household sizes ranging from two to seven members. Exponential-family random graph models (ERGMs) were fitted to the within-household contact networks to reveal the processes driving contact between household members, both on weekdays and weekends. The ERGMs showed a high degree of clustering and, specifically on weekdays, decreasing connectedness with increasing household size. Furthermore, we found that the odds of a contact between older siblings and between father and child are smaller than for any other pair. The epidemic simulation results suggest that within-household contact density is the main driver of differences in epidemic spread between complete and empirical-based household contact networks. The homogeneous mixing assumption may therefore be an adequate characterization of the within-household contact structure for the purpose of epidemic simulations. However, ignoring the contact density when inferring based on an epidemic model will result in biased estimates of within-household transmission rates. Further research regarding the implementation of within-household contact networks in epidemic models is necessary.European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme [682540]; IAP Research Network of the Belgian State (Belgian Science Policy) [P7/06]; AXA Research Fund; University of Antwerp Scientific Chair in Evidence-Based Vaccinology; Flemish government; Research Foundation Flanders (FWO) [G043815N]; University of Antwerp; Antwerp Study Centre for Infectious Diseases (ASCID)epidemic model; household contact network; ERGM; random mixing; infectious diseas

Modelling the early phase of the Belgian COVID-19 epidemic using a stochastic compartmental model and studying its implied future trajectories

Following the onset of the ongoing COVID-19 pandemic throughout the world, a large fraction of the global population is or has been under strict measures of physical distancing and quarantine, with many countries being in partial or full lockdown. These measures are imposed in order to reduce the spread of the disease and to lift the pressure on healthcare systems. Estimating the impact of such interventions as well as monitoring the gradual relaxing of these stringent measures is quintessential to understand how resurgence of the COVID-19 epidemic can be controlled for in the future. In this paper we use a stochastic age-structured discrete time compartmental model to describe the transmission of COVID-19 in Belgium. Our model explicitly accounts for age-structure by integrating data on social contacts to (i) assess the impact of the lockdown as implemented on March 13, 2020 on the number of new hospitalizations in Belgium; (ii) conduct a scenario analysis estimating the impact of possible exit strategies on potential future COVID-19 waves. More specifically, the aforementioned model is fitted to hospital admission data, data on the daily number of COVID-19 deaths and serial serological survey data informing the (sero)prevalence of the disease in the population while relying on a Bayesian MCMC approach. Our age-structured stochastic model describes the observed outbreak data well, both in terms of hospitalizations as well as COVID-19 related deaths in the Belgian population. Despite an extensive exploration of various projections for the future course of the epidemic, based on the impact of adherence to measures of physical distancing and a potential increase in contacts as a result of the relaxation of the stringent lockdown measures, a lot of uncertainty remains about the evolution of the epidemic in the next months