Covid-19 has caused hundred of thousands of deaths and an economic damage amounting to trillions of dollars, creating a desire for the rapid development of vaccine. Once available, vaccine is gradually produced, evoking the question on how to distribute it best. While official vaccination guidelines largely focus on the question to whom vaccines should be provided first (e.g. to risk groups), here we propose a strategy for their distribution in time and space, which sequentially prioritizes regions with a high local infection growth rate. To demonstrate this strategy, we develop a simple statistical model describing the time-evolution of infection patterns and their response to vaccination, for infectious diseases like Covid-19. For inhomogeneous infection patterns, locally well-mixed populations and basic reproduction numbers $R_0\sim 1.5-4$ the proposed strategy at least halves the number of deaths in our simulations compared to the standard practice of distributing vaccines proportionally to the population density. For $R_0\sim 1$ we still find a significant increase of the survival rate. The proposed vaccine distribution strategy can be further tested in detailed modelling works and could excite discussions on the importance of the spatiotemporal distribution of vaccines for official guidelines.
Vaccination is essential for the management of infectious diseases, many of which continue to pose devastating public health and economic challenges across the world. However, many vaccines are imperfect having only a partial protective effect in decreasing disease transmission and/or favouring recovery of infected individuals, and possibly exhibiting trade-off between these two properties. Furthermore, population turnover, that is the rate at which individuals enter and exit the population, is another key factor determining the epidemiological dynamics. While these factors have yet been studi…
There are often multiple diseases with cross immunity competing for vaccination resources. Here we investigate the optimal vaccination program in a two-layer Susceptible-Infected-Removed (SIR) model, where two diseases with cross immunity spread in the same population, and vaccines for both diseases are available. We identify three scenarios of the optimal vaccination program, which prevents the outbreaks of both diseases at the minimum cost. We analytically derive a criterion to specify the optimal program based on the costs for different vaccines.
There is great interest in the dynamics of health behaviors in social networks and how they affect collective public health outcomes, but measuring population health behaviors over time and space requires substantial resources. Here, we use publicly available data from 101,853 users of online social media collected over a time period of almost six months to measure the spatio-temporal sentiment towards a new vaccine. We validated our approach by identifying a strong correlation between sentiments expressed online and CDC- estimated vaccination rates by region. Analysis of the network of opinio…
We present a compartmental mathematical model with demography for the spread of the COVID-19 disease, considering also asymptomatic infectious individuals. We compute the basic reproductive ratio of the model and study the local and global stability for it. We solve the model numerically based on the case of Italy. We propose a vaccination model and we derive threshold conditions for preventing infection spread in the case of imperfect vaccines.
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…
Recently, the SARS-CoV-2 variants from the United Kingdom (UK), South Africa, and Brazil have received much attention for their increased infectivity, potentially high virulence, and possible threats to existing vaccines and antibody therapies. The question remains if there are other more infectious variants transmitted around the world. We carry out a large-scale study of 252,874 SARS-CoV-2 genome isolates from patients to identify many other rapidly growing mutations on the spike (S) protein receptor-binding domain (RDB). We reveal that 88 out of 95 significant mutations that were observed m…
Randomized trials of infectious disease interventions, such as vaccines, often focus on groups of connected or potentially interacting individuals. When the pathogen of interest is transmissible between study subjects, interference may occur: individual infection outcomes may depend on treatments received by others. Epidemiologists have defined the primary causal effect of interest -- called the "susceptibility effect" -- as a contrast in infection risk under treatment versus no treatment, while holding exposure to infectiousness constant. A related quantity -- the "direct effect" -- is define…
COVID-19 has devastated the entire global community. Vaccines present an opportunity to mitigate the pandemic; however, the effect of vaccination coupled with the behavioral response of the population is not well understood. We propose a model that incorporates two important dynamically varying population behaviors: level of caution and sense of safety. Level of caution increases with the number of infectious cases, while an increasing sense of safety with increased vaccination lowers precautionary behaviors. To the best of our knowledge, this is the first model that can effectively reproduce …
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…
Defining and identifying causal intervention effects for transmissible infectious disease outcomes is challenging because a treatment -- such as a vaccine -- given to one individual may affect the infection outcomes of others. Epidemiologists have proposed causal estimands to quantify effects of interventions under contagion using a two-person partnership model. These simple conceptual models have helped researchers develop causal estimands relevant to clinical evaluation of vaccine effects. However, many of these partnership models are formulated under structural assumptions that preclude rea…
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…
This study aims to determine an optimal control strategy for vaccine scheduling in COVID-19 pandemic treatment by converting widely acknowledged infectious disease model named SEIR into an optimal control problem. The problem is augmented by adding medication and vaccine limitations to match real-world situations. Two version of the problem is formulated to minimize the number of infected individuals at the same provide the optimal vaccine possible to reduce the susceptible population to a considerably lower state. Optimal control problems are solved using RBF-Galerkin method. These problems a…
The COVID-19 pandemic has influenced the lives of people globally. In the past year many researchers have proposed different models and approaches to explore in what ways the spread of the disease could be mitigated. One of the models that have been used a great deal is the Susceptible-Exposed-Infectious-Recovered (SEIR) model. Some researchers have modified the traditional SEIR model, and proposed new versions of it. However, to the best of our knowledge, the state-of-the-art papers have not considered the effect of different vaccine types, meaning single shot and double shot vaccines, in the…
Population-wide vaccination is critical for containing the SARS-CoV-2 (Covid-19) pandemic when combined with restrictive and prevention measures. In this study, we introduce SAIVR, a mathematical model able to forecast the Covid-19 epidemic evolution during the vaccination campaign. SAIVR extends the widely used Susceptible-Infectious-Removed (SIR) model by considering the Asymptomatic (A) and Vaccinated (V) compartments. The model contains several parameters and initial conditions that are estimated by employing a semi-supervised machine learning procedure. After training an unsupervised neur…
Vaccination against COVID-19 with the recently approved mRNA vaccines BNT162b2 (BioNTech/Pfizer) and mRNA-1273 (Moderna) is currently underway in a large number of countries. However, high incidence rates and rapidly spreading SARS-CoV-2 variants are concerning. In combination with acute supply deficits in Europe in early 2021, the question arises of whether stretching the vaccine, for instance by delaying the second dose, can make a significant contribution to preventing deaths, despite associated risks such as lower vaccine efficacy, the potential emergence of escape mutants, enhancement, wa…
The crisis caused by the COVID-19 outbreak around the globe raised an increasing concern about the ongoing emergence of variants of SARS-CoV-2 that may evade the immune response provided by vaccines. New variants appear due to mutation, and as the cases accumulate, the probability of the emergence of a variant of concern increases. In this article, we propose a modified SIR model with waning immunity that captures the competition of two strain classes of an infectious disease under the effect of vaccination with a highly contagious and deadly strain class emerging from a prior strain due to mu…
We analyze an optimal control version of a simple SIRS epidemiology model. The policy maker can adopt policies to diminish the contact rate between infected and susceptible individuals, at a specific economic cost. The arrival of a vaccine will immediately end the epidemic. Total or partial immunity is modeled, while the contact rate can exhibit a (user specified) seasonality. The problem is solved in a spreadsheet environment. A reasonable parameter selection leads to optimal policies which are similar to those followed by different countries. A mild response relying on eventually reaching a …
We review research papers which use game theory to model the decision making of individuals during an epidemic, attempting to classify the literature and identify the emerging trends in this field. We show that the literature can be classified based on (i) type of population modelling (compartmental or network-based), (ii) frequency of the game (non-iterative or iterative), and (iii) type of strategy adoption (self-evaluation or imitation). We highlight that the choice of model depends on many factors such as the type of immunity the disease confers, the type of immunity the vaccine confers, a…
Analytical expressions for the basic reproduction number, R0, have been obtained in the past for a wide variety of mathematical models for infectious disease spread, along with expressions for the expected final size of an outbreak. However, what has so far not been studied is the average number of infections that descend down the chains of infection begun by each of the individuals infected in an outbreak (we refer to this quantity as the "average number of descendant infections" per infectious individual, or ANDI). ANDI includes not only the number of people that an individual directly conta…
During outbreaks of serious infectious diseases many individuals closely follow media reports of the outbreak and take steps, including self-isolation, to protect themselves from infection and possibly death. Self-isolation can take many forms including restricting local and long-distance travel, using face masks, and choosing to receive a vaccine. We use mathematical modeling to show that public health agencies working together with the media can significantly decrease the severity of an outbreak by providing timely and accurate accounts of the numbers of new infections and deaths. Our model …
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…
With the present highly infectious dominant SARS-CoV-2 strain of B1.1.529 or Omicron spreading around the globe, there is concern that the COVID-19 pandemic will not end soon and that it will be a race against time until a more contagious and virulent variant emerges. One of the most promising approaches for preventing virus propagation is to maintain continuous high vaccination efficacy among the population, thereby strengthening the population protective effect and preventing the majority of infection in the vaccinated population, as is known to occur with the Omicron variant frequently. Cou…
During decades, mathematical models have been used to predict the behavior of physical and biologic systems, and to define strategies aiming the minimization of the effects regarding different types of diseases. In the present days, the development of mathematical models to simulate the dynamic behavior of novel coronavirus disease (COVID-19) is considered an important theme due to the quantity of infected people worldwide. In this work, the aim is to determine an optimal control strategy for vaccine administration in COVID-19 pandemic treatment considering real data from China. For this purpo…
In this work we performed a numerical study of an epidemic model that mimics the endemic state of whooping cough in the pre-vaccine era. We considered a stochastic SIR model on dynamical networks that involve local and global contacts among individuals and analyzed the influence of the network properties on the characterization of the quasi-stationary state. We computed probability density functions (PDF) for infected fraction of individuals and found that they are well fitted by gamma functions, excepted the tails of the distributions that are q-exponentials. We also computed the fluctuation …
We propose a mathematical model to analyze the effects of anti-infection behavior on the equilibrium states of an infectious disease. The anti-infection behavior is incorporated into a classical epidemiological SIR model, by considering the behavior adoption rate across the population as an additional variable. We consider also the effects on the adoption rate produced by the disease evolution, using a dynamic payoff function and an additional differential equation. The equilibrium states of the proposed model have remarkable characteristics: possible coexistence of two locally stable endemic …
The vaccination game is a social dilemma that refers to the conundrum individuals face (to get immunized or not) when the population is exposed to an infectious disease. The model has recently gained much traction due to the COVID-19 pandemic since the public perception of vaccines plays a significant role in disease dynamics. This paper studies the vaccination game in the thermodynamic limit with an analytical method derived from the 1D Ising model called Nash equilibrium mapping. The individual dilemma regarding Vaccination comes from an internal conflict wherein one tries to balance the per…
The COVID-19 pandemic has placed unprecedented demands on local public health units in Ontario, Canada, one of which was the need for in-house epidemiological-modelling capabilities. To address this need, Ontario Tech University and the Durham Region Health Department developed a native Windows desktop app that performs epidemiological modelling of infectious diseases. The app is an implementation of a multi-stratified compartmental epidemiological model that can accommodate multiple virus variants and levels of vaccination, as well as public health measures such as physical distancing, contac…
Stanford University（斯坦福大学）；National University of Singapore（新加坡国立大学）；Imperial College London（帝国理工学院）
Since COVID-19 vaccines became available, no studies have quantified how different disaster evacuation strategies can mitigate pandemic risks in shelters. Therefore, we applied an age-structured epidemiological model, known as the Susceptible-Exposed-Infectious-Recovered (SEIR) model, to investigate to what extent different vaccine uptake levels and the Diversion protocol implemented in Taiwan decrease infections and delay pandemic peak occurrences. Taiwan's Diversion protocol involves diverting those in self-quarantine due to exposure, thus preventing them from mingling with the general publi…
The rapidly spreading Covid-19 that affected almost all countries, was first reported at the end of 2019. As a consequence of its highly infectious nature, countries all over the world have imposed extremely strict measures to control its spread. Since the earliest stages of this major pandemic, academics have done a huge amount of research in order to understand the disease, develop medication, vaccines and tests, and model its spread. Among these studies, a great deal of effort has been invested in the estimation of epidemic parameters in the early stage, for the countries affected by Covid-…
Major advances in public health have resulted from disease prevention. However, prevention of a new infectious disease by vaccination or pharmaceuticals is made difficult by the slow process of vaccine and drug development. We propose an additional intervention that allows rapid control of emerging infectious diseases, and can also be used to eradicate diseases that rely almost exclusively on human-to-human transmission. The intervention is based on (1) testing every individual for the disease, (2) repeatedly, and (3) isolation of infected individuals. We show here that at a sufficient rate of…
The COVID-19 pandemic is the most significant global crisis since World War II that affected almost all the countries of our planet. To control the COVID-19 pandemic outbreak, it is necessary to understand how the virus is transmitted to a susceptible individual and eventually spread in the community. The primary transmission pathway of COVID-19 is human-to-human transmission through infectious droplets. However, a recent study by Greenhalgh et al. (Lancet: 397:1603-1605, 2021) demonstrates 10 scientific reasons behind the airborne transmission of SARS-COV-2. In the present study, we introduce…
The response of many governments to the COVID-19 pandemic has involved measures to control within- and between-household transmission, providing motivation to improve understanding of the absolute and relative risks in these contexts. Here, we perform exploratory, residual-based, and transmission-dynamic household analysis of the Office for National Statistics (ONS) COVID-19 Infection Survey (CIS) data from 26 April 2020 to 15 July 2021 in England. This provides evidence for: (i) temporally varying rates of introduction of infection into households broadly following the trajectory of the overa…
Modelling the interaction between ethnicity and infectious disease transmission dynamics in Aotearoa New Zealand during the first Omicron wave of the COVID-19 pandemic
After more than 6 million deaths worldwide, the ongoing vaccination to conquer the COVID-19 disease is now competing with the emergence of increasingly contagious mutations, repeatedly supplanting earlier strains. Following the near-absence of historical examples of the long-time evolution of infectious diseases under similar circumstances, models are crucial to exemplify possible scenarios. Accordingly, in the present work we systematically generalize the popular susceptible-infected-recovered model to account for mutations leading to repeatedly occurring new strains, which we coarse grain ba…
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 …
COVID-19 in low-tolerance border quarantine systems: impact of the Delta variant of SARS-CoV-2
The University of Melbourne（墨尔本大学）；Melbourne School of Population and Global Health, The University of Melbourne（墨尔本大学人口与全球健康学院）；The Peter Doherty Institute for Infection and Immunity, The Royal Melbourne Hospital and The University of Melbourne（彼得·多赫蒂感染与免疫研究所、皇家墨尔本医院和墨尔本大学）；Department of Infectious Diseases, The Alfred and Central Clinical School, Monash University（莫纳什大学阿尔弗雷德医院和中央临床学院传染病系）；School of Mathematics and Statistics, The University of Melbourne（墨尔本大学数学与统计学院）
Sensitivity Analysis (SA) is a useful tool to measure the impact of changes in model parameters on the infection dynamics, particularly to quantify the expected efficacy of disease control strategies. SA has only been applied to epidemic models at the population level, ignoring the effect of within-host virus-with-immune-system interactions on the disease spread. Connecting the scales from individual to population can help inform drug and vaccine development. Thus the value of understanding the impact of immunological parameters on epidemiological quantities. Here we consider an age-since-infe…
In the absence of any available vaccines or drugs, prevention of the spread of Coronavirus Disease 2019 (COVID-19) pandemic is being achieved by putting many mitigation measures in place. It is indispensable to have robust and reliable ways of evaluating the effectiveness of these measures. In this work, we assume that, at a very coarse-grained level of description, the overall effect of all the mitigation measures is that we can still describe the spread of the pandemic using the most basic Susceptible-Exposed-Infectious-Removed ($SEIR$) model but with an "effective contact rate" ($β$) which …
Without vaccines and treatments, societies must rely on non-pharmaceutical intervention strategies to control the spread of emerging diseases such as COVID-19. Though complete lockdown is epidemiologically effective, because it eliminates infectious contacts, it comes with significant costs. Several recent studies have suggested that a plausible compromise strategy for minimizing epidemic risk is periodic closure, in which populations oscillate between wide-spread social restrictions and relaxation. However, no underlying theory has been proposed to predict and explain optimal closure periods …
The ongoing novel coronavirus epidemic has been announced a pandemic by the World Health Organization on March 11, 2020, and the Govt. of India has declared a nationwide lockdown from March 25, 2020, to prevent community transmission of COVID-19. Due to absence of specific antivirals or vaccine, mathematical modeling play an important role to better understand the disease dynamics and designing strategies to control rapidly spreading infectious diseases. In our study, we developed a new compartmental model that explains the transmission dynamics of COVID-19. We calibrated our proposed model wi…
Covid-19 is raging a devastating trail with the highest mortality-to-infected ratio ever for a pandemic. Lack of vaccine and therapeutic has rendered social exclusion through lockdown as the singular mode of containment. Harnessing the predictive powers of Machine Learning within a 6 dimensional infection kinetic model, depicting interactive evolution of 6 infection stages - healthy susceptible ($H$), predisposed comorbid susceptible ($P$), infected ($I$), recovered ($R$), herd immunized ($V$) and mortality ($D$) - the model, PHIRVD, provides the first accurate mortality prediction of 18 count…
In the absence of drugs and vaccines, policymakers use non-pharmaceutical interventions such as social distancing to decrease rates of disease-causing contact, with the aim of reducing or delaying the epidemic peak. These measures carry social and economic costs, so societies may be unable to maintain them for more than a short period of time. Intervention policy design often relies on numerical simulations of epidemic models, but comparing policies and assessing their robustness demands clear principles that apply across strategies. Here we derive the theoretically optimal strategy for using …
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…
In the midst of pandemic for respiratory illness, the call for non-pharmaceutical interventions become the highest priority for infectious disease and public health experts, while the race towards vaccine or medical intervention are ongoing. Individuals may modify their behavior and take preventative steps to reduce infection risk in the bid to adhere to the call by government officials and experts. As a result, the existence of relationship between the preliminary and the final transmission rates become feeble. This study evaluates the behavioral changes (mitigation and suppression measures) …
A comparison of short-term probabilistic forecasts for the incidence of COVID-19 using mechanistic and statistical time series models
ETH Zurich（苏黎世联邦理工学院）；University of Bern（伯尔尼大学）；Imperial College London（伦敦帝国理工学院）；LMU Munich（慕尼黑大学）；Munich Center for Machine Learning（慕尼黑机器学习中心）；National University of Singapore（新加坡国立大学）；National University Health System（国立大学医疗系统）；University of Copenhagen（哥本哈根大学）
