An approximate diffusion process for environmental stochasticity in infectious disease transmission modelling.

Modelling the transmission dynamics of an infectious disease is a complex task. Not only it is difficult to accurately model the inherent non-stationarity and heterogeneity of transmission, but it is nearly impossible to describe, mechanistically, changes in extrinsic environmental factors including public behaviour and seasonal fluctuations. An elegant approach to capturing environmental stochasticity is to model the force of infection as a stochastic process. However, inference in this context requires solving a computationally expensive "missing data" problem, using data-augmentation techniques. We propose to model the time-varying transmission-potential as an approximate diffusion process using a path-wise series expansion of Brownian motion. This approximation replaces the "missing data" imputation step with the inference of the expansion coefficients: a simpler and computationally cheaper task. We illustrate the merit of this approach through three examples: modelling influenza using a canonical SIR model, capturing seasonality using a SIRS model, and the modelling of COVID-19 pandemic using a multi-type SEIR model.

Modeling SARS-CoV-2 nucleotide mutations as a stochastic process.

This study analyzes the SARS-CoV-2 genome sequence mutations by modeling its nucleotide mutations as a stochastic process in both the time-series and spatial domain of the gene sequence. In the time-series model, a Markov Chain embedded Poisson random process characterizes the mutation rate matrix, while the spatial gene sequence model delineates the distribution of mutation inter-occurrence distances. Our experiment focuses on five key variants of concern that had become a global concern due to their high transmissibility and virulence. The time-series results reveal distinct asymmetries in mutation rate and propensities among different nucleotides and across different strains, with a mean mutation rate of approximately 2 mutations per month. In particular, our spatial gene sequence results reveal some novel biological insights on the characteristic distribution of mutation inter-occurrence distances, which display a notable pattern similar to other natural diseases. Our findings contribute interesting insights to the underlying biological mechanism of SARS-CoV-2 mutations, bringing us one step closer to improving the accuracy of existing mutation prediction models. This research could also potentially pave the way for future work in adopting similar spatial random process models and advanced spatial pattern recognition algorithms in order to characterize mutations on other different kinds of virus families.

Assessing the impact of non-pharmaceutical interventions on SARS-CoV-2 transmission in Switzerland.

Following the rapid dissemination of COVID-19 cases in Switzerland, large-scale non-pharmaceutical interventions (NPIs) were implemented by the cantons and the federal government between 28 February and 20 March 2020. Estimates of the impact of these interventions on SARS-CoV-2 transmission are critical for decision making in this and future outbreaks. We here aim to assess the impact of these NPIs on disease transmission by estimating changes in the basic reproduction number (R0) at national and cantonal levels in relation to the timing of these NPIs. We estimated the time-varying R0 nationally and in eleven cantons by fitting a stochastic transmission model explicitly simulating within-hospital dynamics. We used individual-level data from more than 1000 hospitalised patients in Switzerland and public daily reports of hospitalisations and deaths. We estimated the national R0 to be 2.8 (95% confidence interval 2.1–3.8) at the beginning of the epidemic. Starting from around 7 March, we found a strong reduction in time-varying R0 with a 86% median decrease (95% quantile range [QR] 79–90%) to a value of 0.40 (95% QR 0.3–0.58) in the period of 29 March to 5 April. At the cantonal level, R0 decreased over the course of the epidemic between 53% and 92%. Reductions in time-varying R0 were synchronous with changes in mobility patterns as estimated through smartphone activity, which started before the official implementation of NPIs. We inferred that most of the reduction of transmission is attributable to behavioural changes as opposed to natural immunity, the latter accounting for only about 4% of the total reduction in effective transmission. As Switzerland considers relaxing some of the restrictions of social mixing, current estimates of time-varying R0 well below one are promising. However, as of 24 April 2020, at least 96% (95% QR 95.7–96.4%) of the Swiss population remains susceptible to SARS-CoV-2. These results warrant a cautious relaxation of social distance practices and close monitoring of changes in both the basic and effective reproduction numbers.

Epidemic highs and lows: a stochastic diffusion model for active cases.

We derive a stochastic epidemic model for the evolving density of infective individuals in a large population. Data shows main features of a typical epidemic consist of low periods interspersed with outbreaks of various intensities and duration. In our stochastic differential model, a novel reproductive term combines a factor expressing the recent notion of 'attenuated Allee effect' and a capacity factor is controlling the size of the process. Simulation of this model produces sample paths of the stochastic density of infectives, which behave much like long-time Covid-19 case data of recent years. Writing the process as a stochastic diffusion allows us to derive its stationary distribution, showing the relative time spent in low levels and in outbursts. Much of the behaviour of the density of infectives can be understood in terms of the interacting drift and diffusion coefficient processes, or, alternatively, in terms of the balance between noise level and the attenuation parameter of the Allee effect. Unexpected results involve the effect of increasing overall noise variance on the density of infectives, in particular on its level-crossing function.

Epidemic modeling with heterogeneity and social diffusion.

We propose and analyze a family of epidemiological models that extend the classic Susceptible-Infectious-Recovered/Removed (SIR)-like framework to account for dynamic heterogeneity in infection risk. The family of models takes the form of a system of reaction-diffusion equations given populations structured by heterogeneous susceptibility to infection. These models describe the evolution of population-level macroscopic quantities S, I, R as in the classical case coupled with a microscopic variable f, giving the distribution of individual behavior in terms of exposure to contagion in the population of susceptibles. The reaction terms represent the impact of sculpting the distribution of susceptibles by the infection process. The diffusion and drift terms that appear in a Fokker-Planck type equation represent the impact of behavior change both during and in the absence of an epidemic. We first study the mathematical foundations of this system of reaction-diffusion equations and prove a number of its properties. In particular, we show that the system will converge back to the unique equilibrium distribution after an epidemic outbreak. We then derive a simpler system by seeking self-similar solutions to the reaction-diffusion equations in the case of Gaussian profiles. Notably, these self-similar solutions lead to a system of ordinary differential equations including classic SIR-like compartments and a new feature: the average risk level in the remaining susceptible population. We show that the simplified system exhibits a rich dynamical structure during epidemics, including plateaus, shoulders, rebounds and oscillations. Finally, we offer perspectives and caveats on ways that this family of models can help interpret the non-canonical dynamics of emerging infectious diseases, including COVID-19.

Cumulative damage for multi-type epidemics and an application to infectious diseases.

A continuous time multivariate stochastic model is proposed for assessing the damage of a multi-type epidemic cause to a population as it unfolds. The instants when cases occur and the magnitude of their injure are random. Thus, we define a cumulative damage based on counting processes and a multivariate mark process. For a large population we approximate the behavior of this damage process by its asymptotic distribution. Also, we analyze the distribution of the stopping times when the numbers of cases caused by the epidemic attain levels beyond certain thresholds. We focus on introducing some tools for statistical inference on the parameters related with the epidemic. In this regard, we present a general hypothesis test for homogeneity in epidemics and apply it to data of Covid-19 in Chile.

Stochastic dynamical behavior of COVID-19 model based on secondary vaccination.

This paper mainly studies the dynamical behavior of a stochastic COVID-19 model. First, the stochastic COVID-19 model is built based on random perturbations, secondary vaccination and bilinear incidence. Second, in the proposed model, we prove the existence and uniqueness of the global positive solution using random Lyapunov function theory, and the sufficient conditions for disease extinction are obtained. It is analyzed that secondary vaccination can effectively control the spread of COVID-19 and the intensity of the random disturbance can promote the extinction of the infected population. Finally, the theoretical results are verified by numerical simulations.

Dynamics of a stochastic SIRS epidemic model with standard incidence and vaccination.

A stochastic SIRS epidemic model with vaccination is discussed. A new stochastic threshold $ R_0/ $ is determined. When the noise is very low ($ R_0/ < 1 $), the disease becomes extinct, and if $ R_0/ > 1 $, the disease persists. Furthermore, we show that the solution of the stochastic model oscillates around the endemic equilibrium point and the intensity of the fluctuation is proportional to the intensity of the white noise. Computer simulations are used to support our findings.

Correlated stochastic epidemic model for the dynamics of SARS-CoV-2 with vaccination.

In this paper, we propose a mathematical model to describe the influence of the SARS-CoV-2 virus with correlated sources of randomness and with vaccination. The total human population is divided into three groups susceptible, infected, and recovered. Each population group of the model is assumed to be subject to various types of randomness. We develop the correlated stochastic model by considering correlated Brownian motions for the population groups. As the environmental reservoir plays a weighty role in the transmission of the SARS-CoV-2 virus, our model encompasses a fourth stochastic differential equation representing the reservoir. Moreover, the vaccination of susceptible is also considered. Once the correlated stochastic model, the existence and uniqueness of a positive solution are discussed to show the problem's feasibility. The SARS-CoV-2 extinction, as well as persistency, are also examined, and sufficient conditions resulted from our investigation. The theoretical results are supported through numerical/graphical findings.

Modeling the stochastic within-host dynamics SARS-CoV-2 infection with discrete delay.

In this paper, a new mathematical model that describes the dynamics of the within-host COVID-19 epidemic is formulated. We show the stochastic dynamics of Target-Latent-Infected-Virus free within the human body with discrete delay and noise. Positivity and uniqueness of the solutions are established. Our study shows the extinction and persistence of the disease inside the human body through the stability analysis of the disease-free equilibrium [Formula: see text] and the endemic equilibrium [Formula: see text], respectively. Moreover, we show the impact of delay tactics and noise on the extinction of the disease. The most interesting result is even if the deterministic system is inevitably pandemic at a specific point, extinction will become possible in the stochastic version of our model.

Persistent Correlation in Cellular Noise Determines Longevity of Viral Infections.

The slowly decaying viral dynamics, even after 2-3 weeks from diagnosis, is one of the characteristics of COVID-19 infection that is still unexplored in theoretical and experimental studies. This long-lived characteristic of viral infections in the framework of inherent variations or noise present at the cellular level is often overlooked. Therefore, in this work, we aim to understand the effect of these variations by proposing a stochastic non-Markovian model that not only captures the coupled dynamics between the immune cells and the virus but also enables the study of the effect of fluctuations. Numerical simulations of our model reveal that the long-range temporal correlations in fluctuations dictate the long-lived dynamics of a viral infection and, in turn, also affect the rates of immune response. Furthermore, predictions of our model system are in agreement with the experimental viral load data of COVID-19 patients from various countries.

A modified Susceptible-Infected-Recovered model for observed under-reported incidence data.

Fitting Susceptible-Infected-Recovered (SIR) models to incidence data is problematic when not all infected individuals are reported. Assuming an underlying SIR model with general but known distribution for the time to recovery, this paper derives the implied differential-integral equations for observed incidence data when a fixed fraction of newly infected individuals are not observed. The parameters of the resulting system of differential equations are identifiable. Using these differential equations, we develop a stochastic model for the conditional distribution of current disease incidence given the entire past history of reported cases. We estimate the model parameters using Bayesian Markov Chain Monte-Carlo sampling of the posterior distribution. We use our model to estimate the transmission rate and fraction of asymptomatic individuals for the current Coronavirus 2019 outbreak in eight American Countries: the United States of America, Brazil, Mexico, Argentina, Chile, Colombia, Peru, and Panama, from January 2020 to May 2021. Our analysis reveals that the fraction of reported cases varies across all countries. For example, the reported incidence fraction for the United States of America varies from 0.3 to 0.6, while for Brazil it varies from 0.2 to 0.4.

Transient dynamics of infection transmission in a simulated intensive care unit.

Healthcare-associated infections (HAIs) remain a serious public health problem. In previous work, two models of an intensive care unit (ICU) showed that differing population structures had markedly different rates of Staphylococcus aureus (MRSA) transmission. One explanation for this difference is the models having differing long-term equilbrium dynamics, resulting from different basic reproductive numbers, R0. We find in this system however that this is not the case, and that both models had the same value for R0. Instead, short-term, transient dynamics, characterizing a series of small, self-limiting outbreaks caused by pathogen reintroduction were responsible for the differences. These results show the importance of these short-term factors for disease systems where reintroduction events are frequent, even if they are below the epidemic threshold. Further, we examine how subtle changes in how a hospital is organized-or how a model assumes a hospital is organized-in terms of the admission of new patients may impact transmission rates. This has implications for both novel pathogens introduced into ICUs, such as Ebola, MERS or COVID-19, as well as existing healthcare-associated infections such as carbapenem-resistant Enterobacteriaceae.

Asymptotic behavior of the solutions for a stochastic SIRS model with information intervention.

In this paper, a stochastic SIRS epidemic model with information intervention is considered. By constructing an appropriate Lyapunov function, the asymptotic behavior of the solutions for the proposed model around the equilibria of the deterministic model is investigated. We show the average in time of the second moment of the solutions of the stochastic system is bounded for a relatively small noise. Furthermore, we find that information interaction response rate plays an active role in disease control, and as the intensity of the response increases, the number of infected population decreases, which is beneficial for disease control.

Dynamics of a stochastic COVID-19 epidemic model considering asymptomatic and isolated infected individuals.

Coronavirus disease (COVID-19) has a strong influence on the global public health and economics since the outbreak in 2020. In this paper, we study a stochastic high-dimensional COVID-19 epidemic model which considers asymptomatic and isolated infected individuals. Firstly we prove the existence and uniqueness for positive solution to the stochastic model. Then we obtain the conditions on the extinction of the disease as well as the existence of stationary distribution. It shows that the noise intensity conducted on the asymptomatic infections and infected with symptoms plays an important role in the disease control. Finally numerical simulation is carried out to illustrate the theoretical results, and it is compared with the real data of India.

Impact of information and Lévy noise on stochastic COVID-19 epidemic model under real statistical data.

In this paper, we consider the dynamical behaviour of a stochastic coronavirus (COVID-19) susceptible-infected-removed epidemic model with the inclusion of the influence of information intervention and Lévy noise. The existence and uniqueness of the model positive solution are proved. Then, we establish a stochastic threshold as a sufficient condition for the extinction and persistence in mean of the disease. Based on the available COVID-19 data, the parameters of the model were estimated and we fit the model with real statistics. Finally, numerical simulations are presented to support our theoretical results.

Threshold dynamics of a stochastic SIHR epidemic model of COVID-19 with general population-size dependent contact rate.

In this paper, we propose a stochastic SIHR epidemic model of COVID-19. A basic reproduction number $ R_{0}^{s} $ is defined to determine the extinction or persistence of the disease. If $ R_{0}^{s} < 1 $, the disease will be extinct. If $ R_{0}^{s} > 1 $, the disease will be strongly stochastically permanent. Based on realistic parameters of COVID-19, we numerically analyze the effect of key parameters such as transmission rate, confirmation rate and noise intensity on the dynamics of disease transmission and obtain sensitivity indices of some parameters on $ R_{0}^{s} $ by sensitivity analysis. It is found that: 1) The threshold level of deterministic model is overestimated in case of neglecting the effect of environmental noise; 2) The decrease of transmission rate and the increase of confirmed rate are beneficial to control the spread of COVID-19. Moreover, our sensitivity analysis indicates that the parameters $ \beta $, $ \sigma $ and $ \delta $ have significantly effects on $ R_0/ $.

Outbreak Size Distribution in Stochastic Epidemic Models.

Motivated by recent epidemic outbreaks, including those of COVID-19, we solve the canonical problem of calculating the dynamics and likelihood of extensive outbreaks in a population within a large class of stochastic epidemic models with demographic noise, including the susceptible-infected-recovered (SIR) model and its general extensions. In the limit of large populations, we compute the probability distribution for all extensive outbreaks, including those that entail unusually large or small (extreme) proportions of the population infected. Our approach reveals that, unlike other well-known examples of rare events occurring in discrete-state stochastic systems, the statistics of extreme outbreaks emanate from a full continuum of Hamiltonian paths, each satisfying unique boundary conditions with a conserved probability flux.

Evolution of resistance to COVID-19 vaccination with dynamic social distancing.

The greatest hope for a return to normalcy following the COVID-19 pandemic is worldwide vaccination. Yet, a relaxation of social distancing that allows increased transmissibility, coupled with selection pressure due to vaccination, will probably lead to the emergence of vaccine resistance. We analyse the evolutionary dynamics of COVID-19 in the presence of dynamic contact reduction and in response to vaccination. We use infection and vaccination data from six different countries. We show that under slow vaccination, resistance is very likely to appear even if social distancing is maintained. Under fast vaccination, the emergence of mutants can be prevented if social distancing is maintained during vaccination. We analyse multiple human factors that affect the evolutionary potential of the virus, including the extent of dynamic social distancing, vaccination campaigns, vaccine design, boosters and vaccine hesitancy. We provide guidelines for policies that aim to minimize the probability of emergence of vaccine-resistant variants.

Sensitivity of SARS-CoV-2 Life Cycle to IFN Effects and ACE2 Binding Unveiled with a Stochastic Model.

Mathematical modelling of infection processes in cells is of fundamental interest. It helps to understand the SARS-CoV-2 dynamics in detail and can be useful to define the vulnerability steps targeted by antiviral treatments. We previously developed a deterministic mathematical model of the SARS-CoV-2 life cycle in a single cell. Despite answering many questions, it certainly cannot accurately account for the stochastic nature of an infection process caused by natural fluctuation in reaction kinetics and the small abundance of participating components in a single cell. In the present work, this deterministic model is transformed into a stochastic one based on a Markov Chain Monte Carlo (MCMC) method. This model is employed to compute statistical characteristics of the SARS-CoV-2 life cycle including the probability for a non-degenerate infection process. Varying parameters of the model enables us to unveil the inhibitory effects of IFN and the effects of the ACE2 binding affinity. The simulation results show that the type I IFN response has a very strong effect on inhibition of the total viral progeny whereas the effect of a 10-fold variation of the binding rate to ACE2 turns out to be negligible for the probability of infection and viral production.