Disentangling the role of virus infectiousness and awareness-based human behavior during the early phase of the COVID-19 pandemic in the European Union.

In this work, we manage to disentangle the role of virus infectiousness and awareness-based human behavior in the COVID-19 pandemic. Using Bayesian inference, we quantify the uncertainty of a state-space model whose propagator is based on an unusual SEIR-type model since it incorporates the effective population fraction as a parameter. Within the Markov Chain Monte Carlo (MCMC) algorithm, Unscented Kalman Filter (UKF) may be used to evaluate the likelihood approximately. UKF is a suitable strategy in many cases, but it is not well-suited to deal with non-negativity restrictions on the state variables. To overcome this difficulty, we modify the UKF, conveniently truncating Gaussian distributions, which allows us to deal with such restrictions. We use official infection notification records to analyze the first 22 weeks of infection spread in each of the 27 countries of the European Union (EU). It is known that such records are the primary source of information to assess the early evolution of the pandemic and, at the same time, usually suffer underreporting and backlogs. Our model explicitly accounts for uncertainty in the dynamic model parameters, the dynamic model adequacy, and the infection observation process. We argue that this modeling paradigm allows us to disentangle the role of the contact rate, the effective population fraction, and the infection observation probability across time and space with an imperfect first principles model. Our findings agree with phylogenetic evidence showing little variability in the contact rate, or virus infectiousness, across EU countries during the early phase of the pandemic, highlighting the advantage of incorporating the effective population fraction into pandemic modeling for heterogeneity in both human behavior and reporting. Finally, to evaluate the consistency of our data assimilation method, we performed a forecast that adequately fits the actual data. Statement of significance: Data-driven and model-based epidemiological studies aimed at learning the number of people infected early during a pandemic should explicitly consider the behavior-induced effective population effect. Indeed, the non-isolated, or effective, fraction of the population during the early phase of the pandemic is time-varying, and first-principles modeling with quantified uncertainty is imperative for an adequate analysis across time and space. We argue that, although good inference results may be obtained using the classical SEIR type model, the model posed in this work has allowed us to disentangle the role of virus infectiousness and awareness-based human behavior during the early phase of the COVID-19 pandemic in the European Union from official infection notification records.

Filtering and improved Uncertainty Quantification in the dynamic estimation of effective reproduction numbers.

The effective reproduction number Rt measures an infectious disease's transmissibility as the number of secondary infections in one reproduction time in a population having both susceptible and non-susceptible hosts. Current approaches do not quantify the uncertainty correctly in estimating Rt, as expected by the observed variability in contagion patterns. We elaborate on the Bayesian estimation of Rt by improving on the Poisson sampling model of Cori et al. (2013). By adding an autoregressive latent process, we build a Dynamic Linear Model on the log of observed Rts, resulting in a filtering type Bayesian inference. We use a conjugate analysis, and all calculations are explicit. Results show an improved uncertainty quantification on the estimation of Rt's, with a reliable method that could safely be used by non-experts and within other forecasting systems. We illustrate our approach with recent data from the current COVID19 epidemic in Mexico.

Bayesian sequential data assimilation for COVID-19 forecasting.

We introduce a Bayesian sequential data assimilation and forecasting method for non-autonomous dynamical systems. We applied this method to the current COVID-19 pandemic. It is assumed that suitable transmission, epidemic and observation models are available and previously validated. The transmission and epidemic models are coded into a dynamical system. The observation model depends on the dynamical system state variables and parameters, and is cast as a likelihood function. The forecast is sequentially updated over a sliding window of epidemic records as new data becomes available. Prior distributions for the state variables at the new forecasting time are assembled using the dynamical system, calibrated for the previous forecast. Epidemic outbreaks are non-autonomous dynamical systems depending on human behavior, viral evolution and climate, among other factors, rendering it impossible to make reliable long-term epidemic forecasts. We show our forecasting method's performance using a SEIR type model and COVID-19 data from several Mexican localities. Moreover, we derive further insights into the COVID-19 pandemic from our model predictions. The rationale of our approach is that sequential data assimilation is an adequate compromise between data fitting and dynamical system prediction.

Bayesian analysis of Glucose dynamics during the Oral Glucose Tolerance Test (OGTT).

This paper proposes a model that considers the action and timing of insulin and glucagon in glucose homeostasis after an oral stimulus. We use the Bayesian paradigm to infer kinetic rates, namely insulin and glucagon secretion, gastrointestinal emptying, and basal glucose concentration in blood. We identify two insulin scores related to glucose concentration in both blood and the gastrointestinal tract. The scores allow us to suggest a classification for individuals with impaired insulin sensitivity.

Forecasting hospital demand in metropolitan areas during the current COVID-19 pandemic and estimates of lockdown-induced 2nd waves.

We present a forecasting model aim to predict hospital occupancy in metropolitan areas during the current COVID-19 pandemic. Our SEIRD type model features asymptomatic and symptomatic infections with detailed hospital dynamics. We model explicitly branching probabilities and non-exponential residence times in each latent and infected compartments. Using both hospital admittance confirmed cases and deaths, we infer the contact rate and the initial conditions of the dynamical system, considering breakpoints to model lockdown interventions and the increase in effective population size due to lockdown relaxation. The latter features let us model lockdown-induced 2nd waves. Our Bayesian approach allows us to produce timely probabilistic forecasts of hospital demand. We have applied the model to analyze more than 70 metropolitan areas and 32 states in Mexico.

A Bayesian Outbreak Detection Method for Influenza-Like Illness.

Epidemic outbreak detection is an important problem in public health and the development of reliable methods for outbreak detection remains an active research area. In this paper we introduce a Bayesian method to detect outbreaks of influenza-like illness from surveillance data. The rationale is that, during the early phase of the outbreak, surveillance data changes from autoregressive dynamics to a regime of exponential growth. Our method uses Bayesian model selection and Bayesian regression to identify the breakpoint. No free parameters need to be tuned. However, historical information regarding influenza-like illnesses needs to be incorporated into the model. In order to show and discuss the performance of our method we analyze synthetic, seasonal, and pandemic outbreak data.

Towards uncertainty quantification and inference in the stochastic SIR epidemic model.

In this paper we address the problem of estimating the parameters of Markov jump processes modeling epidemics and introduce a novel method to conduct inference when data consists on partial observations in one of the state variables. We take the classical stochastic SIR model as a case study. Using the inverse-size expansion of van Kampen we obtain approximations for the first and second moments of the state variables. These approximate moments are in turn matched to the moments of an inputed Generic Discrete distribution aimed at generating an approximate likelihood that is valid both for low count or high count data. We conduct a full Bayesian inference using informative priors. Estimations and predictions are obtained both in a synthetic data scenario and in two Dengue fever case studies.

First principles modeling of nonlinear incidence rates in seasonal epidemics.

In this paper we used a general stochastic processes framework to derive from first principles the incidence rate function that characterizes epidemic models. We investigate a particular case, the Liu-Hethcote-van den Driessche's (LHD) incidence rate function, which results from modeling the number of successful transmission encounters as a pure birth process. This derivation also takes into account heterogeneity in the population with regard to the per individual transmission probability. We adjusted a deterministic SIRS model with both the classical and the LHD incidence rate functions to time series of the number of children infected with syncytial respiratory virus in Banjul, Gambia and Turku, Finland. We also adjusted a deterministic SEIR model with both incidence rate functions to the famous measles data sets from the UK cities of London and Birmingham. Two lines of evidence supported our conclusion that the model with the LHD incidence rate may very well be a better description of the seasonal epidemic processes studied here. First, our model was repeatedly selected as best according to two different information criteria and two different likelihood formulations. The second line of evidence is qualitative in nature: contrary to what the SIRS model with classical incidence rate predicts, the solution of the deterministic SIRS model with LHD incidence rate will reach either the disease free equilibrium or the endemic equilibrium depending on the initial conditions. These findings along with computer intensive simulations of the models' Poincaré map with environmental stochasticity contributed to attain a clear separation of the roles of the environmental forcing and the mechanics of the disease transmission in shaping seasonal epidemics dynamics.

Parameter estimation of some epidemic models. The case of recurrent epidemics caused by respiratory syncytial virus.

The research presented in this paper addresses the problem of fitting a mathematical model to epidemic data. We propose an implementation of the Landweber iteration to solve locally the arising parameter estimation problem. The epidemic models considered consist of suitable systems of ordinary differential equations. The results presented suggest that the inverse problem approach is a reliable method to solve the fitting problem. The predictive capabilities of this approach are demonstrated by comparing simulations based on estimation of parameters against real data sets for the case of recurrent epidemics caused by the respiratory syncytial virus in children.