Data-driven mathematical modeling approaches for COVID-19: A survey.

In this review, we successively present the methods for phenomenological modeling of the evolution of reported and unreported cases of COVID-19, both in the exponential phase of growth and then in a complete epidemic wave. After the case of an isolated wave, we present the modeling of several successive waves separated by endemic stationary periods. Then, we treat the case of multi-compartmental models without or with age structure. Eventually, we review the literature, based on 260 articles selected in 11 sections, ranging from the medical survey of hospital cases to forecasting the dynamics of new cases in the general population. This review favors the phenomenological approach over the mechanistic approach in the choice of references and provides simulations of the evolution of the number of observed cases of COVID-19 for 10 states (California, China, France, India, Israel, Japan, New York, Peru, Spain and United Kingdom).

Stochastic EM algorithm for partially observed stochastic epidemics with individual heterogeneity.

We develop a stochastic epidemic model progressing over dynamic networks, where infection rates are heterogeneous and may vary with individual-level covariates. The joint dynamics are modeled as a continuous-time Markov chain such that disease transmission is constrained by the contact network structure, and network evolution is in turn influenced by individual disease statuses. To accommodate partial epidemic observations commonly seen in real-world data, we propose a stochastic EM algorithm for inference, introducing key innovations that include efficient conditional samplers for imputing missing infection and recovery times which respect the dynamic contact network. Experiments on both synthetic and real datasets demonstrate that our inference method can accurately and efficiently recover model parameters and provide valuable insight at the presence of unobserved disease episodes in epidemic data.

Edge effects in spatial infectious disease models.

Epidemic models serve as a useful analytical tool to study how a disease behaves in a given population. Individual-level models (ILMs) can incorporate individual-level covariate information including spatial information, accounting for heterogeneity within the population. However, the high-level data required to parameterize an ILM may often be available only for a sub-population of a larger population (e.g., a given county, province, or country). As a result, parameter estimates may be affected by edge effects caused by infection originating from outside the observed population. Here, we look at how such edge effects can bias parameter estimates for within the context of spatial ILMs, and suggest a method to improve model fitting in the presence of edge effects when some global measure of epidemic severity is available from the unobserved part of the population. We apply our models to simulated data, as well as data from the UK 2001 foot-and-mouth disease epidemic.

Individual-level models of disease transmission incorporating piecewise spatial risk functions.

Modelling epidemics is crucial for understanding the emergence, transmission, impact and control of diseases. Spatial individual-level models (ILMs) that account for population heterogeneity are a useful tool, accounting for factors such as location, vaccination status and genetic information. Parametric forms for spatial risk functions, or kernels, are often used, but rely on strong assumptions about underlying transmission mechanisms. Here, we propose a class of non-parametric spatial disease transmission model, fitted within a Bayesian Markov chain Monte Carlo (MCMC) framework, allowing for more flexible assumptions when estimating the effect on spatial distance and infection risk. We focus upon two specific forms of non-parametric spatial infection kernel: piecewise constant and piecewise linear. Although these are relatively simple forms, we find them to produce results in line with, or superior to, parametric spatial ILMs. The performance of these models is examined using simulated data, including under circumstances of model misspecification, and then applied to data from the UK 2001 foot-and-mouth disease.

Instabilities and self-organization in spatiotemporal epidemic dynamics driven by nonlinearity and noise.

Theoretical analysis of epidemic dynamics has attracted significant attention in the aftermath of the COVID-19 pandemic. In this article, we study dynamic instabilities in a spatiotemporal compartmental epidemic model represented by a stochastic system of coupled partial differential equations (SPDE). Saturation effects in infection spread-anchored in physical considerations-lead to strong nonlinearities in the SPDE. Our goal is to study the onset of dynamic, Turing-type instabilities, and the concomitant emergence of steady-state patterns under the interplay between three critical model parameters-the saturation parameter, the noise intensity, and the transmission rate. Employing a second-order perturbation analysis to investigate stability, we uncover both diffusion-driven and noise-induced instabilities and corresponding self-organized distinct patterns of infection spread in the steady state. We also analyze the effects of the saturation parameter and the transmission rate on the instabilities and the pattern formation. In summary, our results indicate that the nuanced interplay between the three parameters considered has a profound effect on the emergence of dynamical instabilities and therefore on pattern formation in the steady state. Moreover, due to the central role played by the Turing phenomenon in pattern formation in a variety of biological dynamic systems, the results are expected to have broader significance beyond epidemic dynamics.

Repetition in social contacts: implications in modelling the transmission of respiratory infectious diseases in pre-pandemic and pandemic settings.

The spread of viral respiratory infections is intricately linked to human interactions, and this relationship can be characterized and modelled using social contact data. However, many analyses tend to overlook the recurrent nature of these contacts. To bridge this gap, we undertake the task of describing individuals' contact patterns over time by characterizing the interactions made with distinct individuals during a week. Moreover, we gauge the implications of this temporal reconstruction on disease transmission by juxtaposing it with the assumption of random mixing over time. This involves the development of an age-structured individual-based model, using social contact data from a pre-pandemic scenario (the POLYMOD study) and a pandemic setting (the Belgian CoMix study), respectively. We found that accounting for the frequency of contacts impacts the number of new, distinct, contacts, revealing a lower total count than a naive approach, where contact repetition is neglected. As a consequence, failing to account for the repetition of contacts can result in an underestimation of the transmission probability given a contact, potentially leading to inaccurate conclusions when using mathematical models for disease control. We, therefore, underscore the necessity of acknowledging contact repetition when formulating effective public health strategies.

Social vs. individual age-dependent costs of imperfect vaccination.

In diseases with long-term immunity, vaccination is known to increase the average age at infection as a result of the decrease in the pathogen circulation. This implies that a vaccination campaign can have negative effects when a disease is more costly (financial or health-related costs) for higher ages. This work considers an age-structured population transmission model with imperfect vaccination. We aim to compare the social and individual costs of vaccination, assuming that disease costs are age-dependent, while the disease's dynamic is age-independent. A model for pathogen deterministic dynamics in a population consisting of juveniles and adults, assumed to be rational agents, is introduced. The parameter region for which vaccination has a positive social impact is fully characterized and the Nash equilibrium of the vaccination game is obtained. Finally, collective strategies designed to promote voluntary vaccination, without compromising social welfare, are discussed.

Fitting Epidemic Models to Data: A Tutorial in Memory of Fred Brauer.

Fred Brauer was an eminent mathematician who studied dynamical systems, especially differential equations. He made many contributions to mathematical epidemiology, a field that is strongly connected to data, but he always chose to avoid data analysis. Nevertheless, he recognized that fitting models to data is usually necessary when attempting to apply infectious disease transmission models to real public health problems. He was curious to know how one goes about fitting dynamical models to data, and why it can be hard. Initially in response to Fred's questions, we developed a user-friendly R package, fitode, that facilitates fitting ordinary differential equations to observed time series. Here, we use this package to provide a brief tutorial introduction to fitting compartmental epidemic models to a single observed time series. We assume that, like Fred, the reader is familiar with dynamical systems from a mathematical perspective, but has limited experience with statistical methodology or optimization techniques.

Approximating reproduction numbers: a general numerical method for age-structured models.

In this paper, we introduce a general numerical method to approximate the reproduction numbers of a large class of multi-group, age-structured, population models with a finite age span. To provide complete flexibility in the definition of the birth and transition processes, we propose an equivalent formulation for the age-integrated state within the extended space framework. Then, we discretize the birth and transition operators via pseudospectral collocation. We discuss applications to epidemic models with continuous and piecewise continuous rates, with different interpretations of the age variable (e.g., demographic age, infection age and disease age) and the transmission terms (e.g., horizontal and vertical transmission). The tests illustrate that the method can compute different reproduction numbers, including the basic and type reproduction numbers as special cases.

MODELS: a six-step framework for developing an infectious disease model.

Since the COVID-19 pandemic began, a plethora of modeling studies related to COVID-19 have been released. While some models stand out due to their innovative approaches, others are flawed in their methodology. To assist novices, frontline healthcare workers, and public health policymakers in navigating the complex landscape of these models, we introduced a structured framework named MODELS. This framework is designed to detail the essential steps and considerations for creating a dependable epidemic model, offering direction to researchers engaged in epidemic modeling endeavors.

Population dynamics and games of variable size.

This work introduces the concept of Variable Size Game Theory (VSGT), in which the number of players in a game is a strategic decision made by the players themselves. We start by discussing the main examples in game theory: dominance, coexistence, and coordination. We show that the same set of pay-offs can result in coordination-like or coexistence-like games depending on the strategic decision of each player type. We also solve an inverse problem to find a d-player game that reproduces the same fixation pattern of the VSGT. In the sequel, we consider a game involving prosocial and antisocial players, i.e., individuals who tend to play with large groups and small groups, respectively. In this game, a certain task should be performed, that will benefit one of the participants at the expense of the other players. We show that individuals able to gather large groups to perform the task may prevail, even if this task is costly, providing a possible scenario for the evolution of eusociality. The next example shows that different strategies regarding game size may lead to spontaneous separation of different types, a possible scenario for speciation without physical separation (sympatric speciation). In the last example, we generalize to three types of populations from the previous analysis and study compartmental epidemic models: in particular, we recast the SIRS model into the VSGT framework: Susceptibles play 2-player games, while Infectious and Removed play a 1-player game. The SIRS epidemic model is then obtained as the replicator equation of the VSGT. We finish with possible applications of VSGT to be addressed in the future.

Sexually transmitted infections and dating app use.

Incidence of sexually transmitted infections (STIs) is rising sharply in the United States. Between 2014 and 2019, incidence among men and women has increased by 62.8% and 21.4%, respectively, with an estimated 68 million Americans contracting an STI in 2018.a Some human behaviors impacting the expanding STI epidemic are unprotected sex and multiple sexual partners.b Increasing dating app usage has been postulated as a driver for increases in the numbers of people engaging in these behaviors. Using the proposed model, it is estimated that both STI incidence and prevalence for females and males have increased annually by 9%-15% between 2015 and 2019 due to dating apps usage, and that STI incidence and prevalence will continue to increase in the future. The model is also used to assess the possible benefit of in-app prevention campaigns.ahttps://www.cdc.gov/nchhstp/newsroom/fact-sheets/std/STI-Incidence-Prevalence-Cost-Factsheet.htmbA. N. Sawyer, E. R. Smith, and E. G. Benotsch. Dating application use and sexual risk behavior among young adults. Sexuality Research and Social Policy, 15:183-191, 2018.

Modelling contagious viral dynamics: a kinetic approach based on mutual utility.

The temporal evolution of a contagious viral disease is modelled as the dynamic progression of different classes of population with individuals interacting pairwise. This interaction follows a binary mechanism typical of kinetic theory, wherein agents aim to improve their condition with respect to a mutual utility target. To this end, we introduce kinetic equations of Boltzmann-type to describe the time evolution of the probability distributions of the multi-agent system. The interactions between agents are defined using principles from price theory, specifically employing Cobb-Douglas utility functions for binary exchange and the Edgeworth box to depict the common exchange area where utility increases for both agents. Several numerical experiments presented in the paper highlight the significance of this mechanism in driving the phenomenon toward endemicity.

Detecting changes in the transmission rate of a stochastic epidemic model.

Throughout the course of an epidemic, the rate at which disease spreads varies with behavioral changes, the emergence of new disease variants, and the introduction of mitigation policies. Estimating such changes in transmission rates can help us better model and predict the dynamics of an epidemic, and provide insight into the efficacy of control and intervention strategies. We present a method for likelihood-based estimation of parameters in the stochastic susceptible-infected-removed model under a time-inhomogeneous transmission rate comprised of piecewise constant components. In doing so, our method simultaneously learns change points in the transmission rate via a Markov chain Monte Carlo algorithm. The method targets the exact model posterior in a difficult missing data setting given only partially observed case counts over time. We validate performance on simulated data before applying our approach to data from an Ebola outbreak in Western Africa and COVID-19 outbreak on a university campus.

Extinction in host-vector infection models and the role of heterogeneity.

For infections that become endemic in a population, the process may appear stable over a long time scale, but stochastic fluctuations can lead to eventual disease extinction. We consider the effects of model parameters and of population heterogeneities upon the expected time to extinction for host-vector disease systems. We find that non-homogeneous host selection by vectors increases persistence times relative to the homogeneous case, and that the effect becomes even more marked when there are strong associations between particular groups of vectors and hosts. Heterogeneity in vector lifespans, in contrast, is found to decrease persistence times relative to the homogeneous case. Neither the basic reproduction number R0, nor the endemic prevalence level in the corresponding deterministic model, is found to be sufficient to predict (for a given population size) time to extinction. The endemic level, in particular, proves a very unreliable guide to the duration of long-term persistence.

Network-based uncertainty quantification for mathematical models in epidemiology.

After the new Coronavirus disease (COVID-19) emerged in the end of January 2020 in Germany, a large number of individuals suffered from severe symptoms and eventually needed intensive care in hospitals. Due to the rapid spread of the disease, the number of deceased individuals increased as well, which is a motivation to prevent as many new infections as possible. Therefore, the knowledge about the current evolution of the virus spread is crucial to predict its future behavior and to react with suitable interventions. In this paper, the evolution of the COVID-19 pandemic in Germany is forecasted by a network-based inference method, in which the interactions of individuals are taken into account using a contact matrix. Then the results are compared to the predictions without considering a contact matrix as well as to the logistic regression, which shows the advantage of incorporating the contact matrix. Furthermore, the basic reproduction number of the pandemic in Germany using a neural network approach is estimated and used for further predictions of the evolution of COVID-19 in Germany. In order to mathematically model the different compartments of the population in the considered regions, the classical SIR model is employed. In this work, we deploy the LASSO (Least Absolute Shrinkage and Selection Operator) for the unknown parameter estimation. Furthermore, we calculate and illustrate the MAPE (Mean Absolute Percentage Error) of the estimations to show the accuracy of the predictions. The results include model parameter estimation and model validation, as well as the outbreak forecasting using network-informed algorithms. Our findings show that the network-inference based approach outperforms the logistic regression as well as the neural network approach and the SIR model calibration without a contact network. Furthermore according to the results, the network-inference based approach is particularly suitable for short- to mid-term predictions, even when there is not much information about the new disease. Moreover, the predictions based on the estimation of the reproduction number in Germany can yield more reliable results with increasing the availability of data, but could not outperform the network-inference based algorithm.

Time scale theory on stability of explicit and implicit discrete epidemic models: applications to Swine flu outbreak.

Time scales theory has been in use since the 1980s with many applications. Only very recently, it has been used to describe within-host and between-hosts dynamics of infectious diseases. In this study, we present explicit and implicit discrete epidemic models motivated by the time scales modeling approach. We use these models to formulate the basic reproduction number, which determines whether an outbreak occurs or the disease dies out. We discuss the stability of the disease-free and endemic equilibrium points using the linearization method and Lyapunov function. Furthermore, we apply our models to swine flu outbreak data to demonstrate that the discrete models can accurately describe the epidemic dynamics. Our comparison analysis shows that the implicit discrete model can best describe the data regardless of the data frequency. In addition, we perform the sensitivity analysis on the key parameters of the models to study how these parameters impact the basic reproduction number.

Optimal vaccination strategies for a heterogeneous population using multiple objectives: The case of L1- and L2-formulations.

The choice of the objective functional in optimization problems coming from biomedical and epidemiological applications plays a key role in optimal control outcomes. In this study, we investigate the role of the objective functional on the structure of the optimal control solution for an epidemic model for sexually transmitted infections that includes a core group with higher sexual activity levels than the rest of the population. An optimal control problem is formulated to find a targeted vaccination program able to control the spread of the infection with minimum vaccine deployment. Both L1- and L2-objectives are considered as an attempt to explore the trade-offs between control dynamics and the functional form characterizing optimality. The results show that the optimal vaccination policies for both the L1- and the L2-formulation share one important qualitative property, that is, immunization of the core group should be prioritized by policymakers to achieve a fast reduction of the epidemic. However, quantitative aspects of this result can be significantly affected depending on the choice of the control weights between formulations. Overall, the results suggest that with appropriate weight constants, the optimal control outcomes are reasonably robust with respect to the L1- or L2-formulation. This is particularly true when the monetary cost of the control policy is substantially lower than the cost associated with the disease burden. Under these conditions, even if the L1-formulation is more realistic from a modeling perspective, the L2-formulation can be used as an approximation and yield qualitatively comparable outcomes.

Structural identifiability analysis of epidemic models based on differential equations: a tutorial-based primer.

The successful application of epidemic models hinges on our ability to estimate model parameters from limited observations reliably. An often-overlooked step before estimating model parameters consists of ensuring that the model parameters are structurally identifiable from the observed states of the system. In this tutorial-based primer, intended for a diverse audience, including students training in dynamic systems, we review and provide detailed guidance for conducting structural identifiability analysis of differential equation epidemic models based on a differential algebra approach using differential algebra for identifiability of systems (DAISY) and Mathematica (Wolfram Research). This approach aims to uncover any existing parameter correlations that preclude their estimation from the observed variables. We demonstrate this approach through examples, including tutorial videos of compartmental epidemic models previously employed to study transmission dynamics and control. We show that the lack of structural identifiability may be remedied by incorporating additional observations from different model states, assuming that the system's initial conditions are known, using prior information to fix some parameters involved in parameter correlations, or modifying the model based on existing parameter correlations. We also underscore how the results of structural identifiability analysis can help enrich compartmental diagrams of differential-equation models by indicating the observed state variables and the results of the structural identifiability analysis.

Angular reproduction numbers improve estimates of transmissibility when disease generation times are misspecified or time-varying.

We introduce the angular reproduction number Ω, which measures time-varying changes in epidemic transmissibility resulting from variations in both the effective reproduction number R, and generation time distribution w. Predominant approaches for tracking pathogen spread infer either R or the epidemic growth rate r. However, R is biased by mismatches between the assumed and true w, while r is difficult to interpret in terms of the individual-level branching process underpinning transmission. R and r may also disagree on the relative transmissibility of epidemics or variants (i.e. rA > rB does not imply RA > RB for variants A and B). We find that Ω responds meaningfully to mismatches and time-variations in w while mostly maintaining the interpretability of R. We prove that Ω > 1 implies R > 1 and that Ω agrees with r on the relative transmissibility of pathogens. Estimating Ω is no more difficult than inferring R, uses existing software, and requires no generation time measurements. These advantages come at the expense of selecting one free parameter. We propose Ω as complementary statistic to R and r that improves transmissibility estimates when w is misspecified or time-varying and better reflects the impact of interventions, when those interventions concurrently change R and w or alter the relative risk of co-circulating pathogens.