Clinical trials of a vaccine during an epidemic face particular challenges, such as the pressure to identify an effective vaccine quickly to control the epidemic, and the effect that time-space-varying infection incidence has on the power of a trial. We illustrate how the operating characteristics of different trial design elements may be evaluated using a network epidemic and trial simulation model, based on COVID-19 and individually randomised two-arm trials with a binary outcome. We show that "ring" recruitment strategies, prioritising participants at high risk of infection, can result in substantial improvement in terms of power, if sufficiently many contacts of observed cases are at high risk. In addition, we introduce a novel method to make more efficient use of the data from the earliest cases of infection observed in the trial, whose infection may have been too early to be vaccine-preventable. Finally, we compare several methods of response-adaptive randomisation, discussing their advantages and disadvantages in this two-arm context and identifying particular adaptation strategies that preserve power and estimation properties, while slightly reducing the number of infections, given an effective vaccine.
We study vaccine control for disease spread on an adaptive network modeling disease avoidance behavior. Control is implemented by adding Poisson distributed vaccination of susceptibles. We show that vaccine control is much more effective in adaptive networks than in static networks due to an interaction between the adaptive network rewiring and the vaccine application. Disease extinction rates using vaccination are computed, and orders of magnitude less vaccine application is needed to drive the disease to extinction in an adaptive network than in a static one.
COVID-19 will be a continuous threat to human population despite having a few vaccines at hand until we reach the endemic state through natural herd immunity and total immunization through universal vaccination. However, the vaccine acts as a practical tool for reducing the massive public health problem and the emerging economic consequences that the continuing COVID -19 epidemic is causing worldwide, while the vaccine efficacy wanes. In this work, we propose and analyze an epidemic model of Susceptible-Exposed-Infected-Recovered-Vaccinated (SEIRV) population taking into account the rate of va…
The dynamics of a SIVR model with power relationship incidence rates $(βI^p S^q)$ is investigated. It is assumed an individual can be susceptible after receiving the first dose of the vaccine, hence a second dose is required to attain permanent immunity. The steady states conditions of the disease-free equilibrium and the endemic equilibrium are critically presented. Numerical simulations are carried out to determine the impact of the exponential parameters $(p;q)$ on infection.
Real-time vaccination following an outbreak can effectively mitigate the damage caused by an infectious disease. However, in many cases, available resources are insufficient to vaccinate the entire at-risk population, logistics result in delayed vaccine deployment, and the interaction between members of different cities facilitates a wide spatial spread of infection. Limited vaccine, time delays, and interaction (or coupling) of cities lead to tradeoffs that impact the overall magnitude of the epidemic. These tradeoffs mandate investigation of optimal strategies that minimize the severity of t…
Population heterogeneity, especially in individuals' contact networks, plays an important role in transmission dynamics of infectious diseases. For vaccine-preventable diseases, outstanding issues like vaccine hesitancy and availability of vaccines further lead to nonuniform coverage among groups, not to mention the efficacy of vaccines and the mixing pattern varying from one group to another. As the ongoing COVID-19 pandemic transitions to endemicity, it is of interest and significance to understand the impact of aforementioned population heterogeneity on the emergence and persistence of epid…
SIRS epidemic models assume that individual immunity (from infection and vaccination) wanes in one big leap, from complete immunity to complete susceptibility. For many diseases immunity on the contrary wanes gradually, something that's become even more evident during COVID-19 pandemic where also recently infected have a reinfection risk, and where booster vaccines are given to increase immunity. This paper considers an epidemic model allowing for such gradual waning of immunity (either linear or exponential waning) thereby extending SIRS epidemics, and also incorporates vaccination. The two v…
How to prevent the spread of human diseases is a great challenge for the scientific community and so far there are many studies in which immunization strategies have been developed. However, these kind of strategies usually do not consider that medical institutes may have limited vaccine resources available. In this manuscript, we explore the Susceptible-Infected-Recovered (SIR) model with local dynamic vaccination, and considering limited vaccines. In this model, susceptibles in contact with an infected individual, are vaccinated -with probability $ω$- and then get infected -with probability …
The success of a vaccination program is crucially dependent on its adoption by a critical fraction of the population, as the resulting herd immunity prevents future outbreaks of an epidemic. However, the effectiveness of a campaign can engender its own undoing if individuals choose to not get vaccinated in the belief that they are protected by herd immunity. Although this may appear to be an optimal decision, based on a rational appraisal of cost and benefits to the individual, it exposes the population to subsequent outbreaks. We investigate if voluntary vaccination can emerge in a an integra…
We present a differential equations model in which contagious disease transmission is affected by contagious fear of the disease and contagious fear of the control, in this case vaccine. The three contagions are coupled. The two fears evolve and interact in ways that shape distancing behavior, vaccine uptake, and their relaxation. These behavioral dynamics in turn can amplify or suppress disease transmission, which feeds back to affect behavior. The model reveals several coupled contagion mechanisms for multiple epidemic waves. Methodologically, the paper advances infectious disease modeling b…
The resurgence of measles is largely attributed to the decline in vaccine adoption and the increase in mobility. Although the vaccine for measles is readily available and highly successful, its current adoption is not adequate to prevent epidemics. Vaccine adoption is directly affected by individual vaccination decisions, and has a complex interplay with the spatial spread of disease shaped by an underlying mobility (travelling) network. In this paper, we model the travelling connectivity as a scale-free network, and investigate dependencies between the network's assortativity and the resultan…
In this work we consider a model of epidemic spreading coupled with an opinion dynamics in a fully-connected population. Regarding the opinion dynamics, the individuals may be in two distinct states, namely in favor or against a vaccination campaign. Individuals against the vaccination follow a standard SIS model, whereas the pro-vaccine individuals can also be in a third compartment, namely Vaccinated. In addition, the opinions change according to the majority-rule dynamics in groups with three individuals. We also consider that the vaccine can give permanent or temporary immunization to the …
Non-pharmaceutical interventions have been critical in the fight against the COVID-19 pandemic. However, these sanitary measures have been partially lifted due to socioeconomic factors causing a worrisome rebound of the epidemic in several countries. In this work, we assess the effectiveness of the mitigation implemented to constrain the spread of SARS-CoV-2 in the Mexican territory during 2020. We also investigate to what extent the initial deployment of the vaccine will help to mitigate the pandemic and reduce the need for social distancing and other mobility restrictions. Our modeling appro…
This work consists of an epidemic model with vaccination coupled with an opinion dynamics. Our objective was to study how disease risk perception can influence opinions about vaccination and therefore the spreading of the disease. Differently from previous works we have considered continuous opinions. The epidemic spreading is governed by a SIS-like model with an extra vaccinated state. In our model individuals vaccinate with a probability proportional to their opinions. The opinions change due to peer influence in pairwise interactions. The epidemic feedback to the opinion dynamics acts as an…
Developing robust, quantitative methods to optimize resource allocations in response to epidemics has the potential to save lives and minimize health care costs. In this paper, we develop and apply a computationally efficient algorithm that enables us to calculate the complete probability distribution for the final epidemic size in a stochastic Susceptible-Infected-Recovered (SIR) model. Based on these results, we determine the optimal allocations of a limited quantity of vaccine between two non-interacting populations. We compare the stochastic solution to results obtained for the traditional…
In this work, to support decision making of immunisation strategies, we propose the inclusion of two vaccination doses in the SEIR model considering a stochastic cellular automaton. We analyse three different scenarios of vaccination: $i) unlimited doses, (ii) limited doses into susceptible individuals, and (iii) limited doses randomly distributed overall individuals. Our results suggest that the number of vaccinations and time to start the vaccination is more relevant than the vaccine efficacy, delay between the first and second doses, and delay between vaccinated groups. The scenario (i) sho…
In this work, we address a multicoupled dynamics on complex networks with tunable structural segregation. Specifically, we work on a networked epidemic spreading under a vaccination campaign with agents in favor and against the vaccine. Our results show that such coupled dynamics exhibits a myriad of phenomena such as nonequilibrium transitions accompanied by bistability. Besides we observe the emergence of an intermediate optimal segregation level where the community structure enhances negative opinions over vaccination but counterintuitively hinders - rather than favoring - the global diseas…
The aim of this work is to investigate the optimal vaccine sharing between two SIR centers in the presence of migration fluxes of susceptibles and infected individuals during the mumps outbreak. Optimality of the vaccine allocation means the minimization of the total number of lost working days during the whole period of epidemic outbreak $[0,t_f]$, which can be described by the functional $Q=\int_0^{t_f}I(t){\rm d}t$ where $I(t)$ stands for the number of infectives at time $t$. We explain the behavior of the optimal allocation, which depends on the model parameters and the amount of available…
Background: To prevent future outbreaks of COVID-19, Australia is pursuing a mass-vaccination approach in which a targeted group of the population comprising healthcare workers, aged-care residents and other individuals at increased risk of exposure will receive a highly effective priority vaccine. The rest of the population will instead have access to a less effective vaccine. Methods: We apply a large-scale agent-based model of COVID-19 in Australia to investigate the possible implications of this hybrid approach to mass-vaccination. The model is calibrated to recent epidemiological and demo…
We define a new parameter to quantify the antigenic distance between two H3N2 influenza strains: we use this parameter to measure antigenic distance between circulating H3N2 strains and the closest vaccine component of the influenza vaccine. For the data between 1971 and 2004, the measure of antigenic distance correlates better with efficacy in humans of the H3N2 influenza A annual vaccine than do current state of the art measures of antigenic distance such as phylogenetic sequence analysis or ferret antisera inhibition assays. We suggest that this measure of antigenic distance could be used t…
The ongoing COVID-19 pandemic calls for a multi-faceted public health response comprising complementary interventions to control the spread of the disease while vaccines and therapies are developed. Many of these interventions need to be informed by epidemic risk predictions given available data, including symptoms, contact patterns, and environmental factors. Here we propose a novel probabilistic formalism based on Individual-Level Models (ILMs) that offers rigorous formulas for the probability of infection of individuals, which can be parameterised via Maximum Likelihood Estimation (MLE) app…
Despite high vaccine coverage, pertussis has re-emerged as a public health concern in many countries. One hypothesis posed for re-emergence is the waning of immunity. In some disease systems, the process of waning immunity can be non-linear, involving a complex relationship between the duration of immunity and subsequent boosting of immunity through asymptomatic re-exposure. We present and analyse a model of infectious disease transmission to examine the interplay between infection and immunity. By allowing the duration of infection-acquired immunity to differ from that of vaccine-acquired imm…
Nowadays, the epidemic of COVID-19 in China is under control. However, the epidemic are developing rapidly around the world. Due to the normal migration of population, China is facing high risk from imported cases. The potential specific medicine and vaccine is still in the process of clinical trials. Currently, controlling the impact of imported cases is the key to prevent new outbreak of COVID-19 in China. In this paper, we propose two impulsive systems to describe the impact of multilateral imported cases of COVID-19. Based on the published data, we simulate and discussed the epidemic trend…
In more than two years since the COVID-19 virus was first detected in China, hundreds of millions of individuals have been infected, and millions have died. Aside from the immediate need for medical solutions (such as vaccines and medications) to treat the epidemic, the Corona pandemic has strengthened the demand for mathematical models that can predict the spread of the pandemic in an ever-changing reality. Here, we present a novel, dynamic particle model based on the basic principles of statistical physics that enables the prediction of the spreading of Covid-19 in the presence of effective …
We use analytical methods to investigate a continuous vaccination strategy effects on the infectious disease dynamics in a closed population and a demographically open population. The methodology and key assumptions are based on Breda et al (2012). We show that the cumulative force of infection for the closed population and the endemic force of infection in the demographically open population can be reduced significantly by combining two factors: the vaccine effectiveness and the vaccination rate. The impact of these factors on the force of infection can transform an endemic steady state into …
Developing accurate and reliable methods to estimate vaccine protection is a key goal in immunology and public health. While several statistical methods have been proposed, their potential inaccuracy in capturing fast intra-seasonal waning of vaccine-induced protection needs to be rigorously investigated. To compare statistical methods for vaccine effectiveness (VE) estimation, we generated simulated data using a multiscale agent-based model of an epidemic with an acute viral infection and differing extents of VE waning. We extended the previously proposed framework for VE measures based on th…
In mid of March 2020, Coronaviruses such as COVID-19 is declared as an international epidemic. More than 125000 confirmed cases and 4,607 death cases have been recorded around more than 118 countries. Unfortunately, a coronavirus vaccine is expected to take at least 18 months if it works at all. Moreover, COVID -19 epidemics can mutate into a more aggressive form. Day level information about the COVID -19 spread is crucial to measure the behavior of this new virus globally. Therefore, this study presents a comparison of day level forecasting models on COVID-19 affected cases using time series …
In this paper we introduce a compartmental epidemic model describing the transmission of the COVID-19 disease in presence of non-mandatory vaccination. The model takes into account the hesitancy and refusal of vaccination. To this aim, we employ the information index, which mimics the idea that individuals take their decision on vaccination based not only on the present but also on the past information about the spread of the disease. Theoretical analysis and simulations show clearly as a voluntary vaccination can certainly reduce the impact of the disease but it is unable to eliminate it. We …
Several epidemiological models have been proposed to study the evolution of COVID-19 pandemic. In this paper, we propose an extension of the SUIHTER model, first introduced in [Parolini et al, Proc R. Soc. A., 2021] to analyse the COVID-19 spreading in Italy, which accounts for the vaccination campaign and the presence of new variants when they become dominant. In particular, the specific features of the variants (e.g. their increased transmission rate) and vaccines (e.g. their efficacy to prevent transmission, hospitalization and death) are modeled, based on clinical evidence. The new model i…
The ongoing COVID-19 pandemic is being responded with various methods, applying vaccines, experimental treatment options, total lockdowns or partial curfews. Weekend curfews is one of the methods to reduce the amount of infected persons and this method is practically applied in some countries such as Turkey. In this study, the effect of weekend curfews on reducing the spread of a contagious disease, such as COVID-19, is modeled using a Monte Carlo algorithm with a hybrid lattice model. In the simulation setup, a fictional country with three towns and 26,610 citizens were used as a model. Resul…
I discuss the so-called SuperSpreader epidemic, for which SARS is the canonical examples (and, perhaps, MERS will be another). I use simulation by an agent-based model as well as the mathematics of multi-type branching-processes to illustrate how the SS epidemic differs from the more familiar uniform epidemic (e.g., caused by influenza). The conclusions may surprise the reader: (a) The SS epidemic must be described by at least two numbers, such as the mean reproductive number (of "secondary" cases caused by a "primary case"), R0, and the variance of same, call it V0; (b) Even if R0 > 1, if V0 …
In this paper we analyze the impact of vaccinations on spread of the COVID-19 virus for different age groups. More specifically we examine the deployment of vaccines in the Nordic countries in a comparative analysis where we analyze factors such as healthcare stress level and severity of disease through new infections, hospitalizations, intensive care unit (ICU) occupancy and deaths. Moreover, we analyze the impact of the various vaccine types, vaccination rate on the spread of the virus in each age group for Denmark, Finland, Iceland, Norway and Sweden from the start of the vaccination period…
COVID-19 has been prevalent worldwide for about 2 years now and has brought unprecedented challenges to our society. Before vaccines were available, the main disease intervention strategies were non-pharmaceutical. Starting December 2020, in Ontario, Canada, vaccines were approved for administering to vulnerable individuals and gradually expanded to all individuals above the age of 12. As the vaccine coverage reached a satisfactory level among the eligible population, normal social activities resumed and schools reopened starting September 2021. However, when schools reopen for in-person learn…
The outbreak of the novel coronavirus, COVID-19, has been declared a pandemic by the WHO. The structures of social contact critically determine the spread of the infection and, in the absence of vaccines, the control of these structures through large-scale social distancing measures appears to be the most effective means of mitigation. Here we use an age-structured SIR model with social contact matrices obtained from surveys and Bayesian imputation to study the progress of the COVID-19 epidemic in India. The basic reproductive ratio R0 and its time-dependent generalization are computed based o…
We develop an agent-based model to assess the cumulative number of deaths during hypothetical Covid-19-like epidemics for various non-pharmaceutical intervention strategies. We consider local and non-local modes of disease transmission. The first simulates transmission through social contacts in the vicinity of the place of residence while the second through social contacts in public places: schools, hospitals, airports, etc., where many people meet, who live in remote geographic locations. Epidemic spreading is modeled as a discrete-time stochastic process on random geometric networks. We use…
We evaluate the efficiency of various heuristic strategies for allocating vaccines against COVID-19 and compare them to strategies found using optimal control theory. Our approach is based on a mathematical model which tracks the spread of disease among different age groups and across different geographical regions, and we introduce a method to combine age-specific contact data to geographical movement data. As a case study, we model the epidemic in the population of mainland Finland utilizing mobility data from a major telecom operator. Our approach allows to determine which geographical regi…
Vaccines are the most powerful pharmaceutical tool to combat the COVID-19 pandemic. While the majority (about 65%) of the German population were fully vaccinated, incidence started growing exponentially in October 2021 with about 41% of recorded new cases aged twelve or above being symptomatic breakthrough infections, presumably also contributing to the dynamics. At the time, it (i) remains elusive how significant this contribution is and (ii) whether targeted non-pharmaceutical interventions (NPIs) may stop the amplification of the ongoing crisis. Here, we estimate that about 67%-76% of all n…
In June 2020, Arizona, U.S., emerged as one of the world's worst coronavirus disease 2019(COVID-19) spots after the stay-at-home order was lifted in the middle of May. However, with the decisions to reimpose restrictions, the number of COVID-19 cases has been declining, and Arizona is considered to be a good model in slowing the epidemic. In this paper, we aimed to examine the COVID-19 situation in Arizona and assess the impact of human mobility change. We constructed the mobility integrated metapopulation susceptible-infectious-removed model and fitted to publicly available datasets on COVID-…
More than any other infectious disease epidemic, the COVID-19 pandemic has been characterized by the generation of large volumes of viral genomic data at an incredible pace due to recent advances in high-throughput sequencing technologies, the rapid global spread of SARS-CoV-2, and its persistent threat to public health. However, distinguishing the most epidemiologically relevant information encoded in these vast amounts of data requires substantial effort across the research and public health communities. Studies of SARS-CoV-2 genomes have been critical in tracking the spread of variants and …
COVID-19 has forced quarantine measures in several countries across the world. These measures have proven to be effective in significantly reducing the prevalence of the virus. To date, no effective treatment or vaccine is available. In the effort of preserving both public health as well as the economical and social textures, France and Italy governments have partially released lockdown measures. Here we extrapolate the long-term behavior of the epidemics in both countries using a Susceptible-Exposed-Infected-Recovered (SEIR) model where parameters are stochastically perturbed to handle the un…
Intent of this research is to explore how mathematical models, specifically Susceptible-Infected-Removed (SIR) model, can be utilized to forecast peak outbreak timeline of COVID-19 epidemic amongst a population of interest starting from the date of first reported case. Till the time of this research, there was no effective and universally accepted vaccine to control transmission and spread of this infection. COVID-19 primarily spreads in population through respiratory droplets from an infected person cough and sneeze which infects people who are in proximity. COVID-19 is spreading contagiously…
Optimizing the impact on the economy of control strategies aiming at containing the spread of COVID-19 is a critical challenge. We use daily new case counts of COVID-19 patients reported by local health administrations from different Metropolitan Statistical Areas (MSAs) within the US to parametrize a model that well describes the propagation of the disease in each area. We then introduce a time-varying control input that represents the level of social distancing imposed on the population of a given area and solve an optimal control problem with the goal of minimizing the impact of social dist…
