When effective medical treatment and vaccination are not available, non-pharmaceutical interventions such as social distancing, home quarantine and far-reaching shutdown of public life are the only available strategies to prevent the spread of epidemics. Based on an extended SEIR (susceptible-exposed-infectious-recovered) model and continuous-time optimal control theory, we compute the optimal non-pharmaceutical intervention strategy for the case that a vaccine is never found and complete containment (eradication of the epidemic) is impossible. In this case, the optimal control must meet competing requirements: First, the minimization of disease-related deaths, and, second, the establishment of a sufficient degree of natural immunity at the end of the measures, in order to exclude a second wave. Moreover, the socio-economic costs of the intervention shall be kept at a minimum. The numerically computed optimal control strategy is a single-intervention scenario that goes beyond heuristically motivated interventions and simple "flattening of the curve." Careful analysis of the computed control strategy reveals, however, that the obtained solution is in fact a tightrope walk close to the stability boundary of the system, where socio-economic costs and the risk of a new outbreak must be constantly balanced against one another. The model system is calibrated to reproduce the initial exponential growth phase of the COVID-19 pandemic in Germany.
Since December 2019, A novel coronavirus (2019-nCoV) has been breaking out in China, which can cause respiratory diseases and severe pneumonia. Mathematical and empirical models relying on the epidemic situation scale for forecasting disease outbreaks have received increasing attention. Given its successful application in the evaluation of infectious diseases scale, we propose a Susceptible-Undiagnosed-Infected-Removed (SUIR) model to offer the effective prediction, prevention, and control of infectious diseases. Our model is a modified susceptible-infected-recovered (SIR) model that injects u…
We highlight the usefulness of city-scale agent-based simulators in studying various non-pharmaceutical interventions to manage an evolving pandemic. We ground our studies in the context of the COVID-19 pandemic and demonstrate the power of the simulator via several exploratory case studies in two metropolises, Bengaluru and Mumbai. Such tools become common-place in any city administration's tool kit in our march towards digital health.
This paper is concerned with the design of intermittent non-pharmaceutical strategies to mitigate the spread of the COVID-19 epidemic exploiting network epidemiological models. Specifically, by studying a variational equation for the dynamics of the infected in a network model of the epidemic spread, we derive, using contractivity arguments, a condition that can be used to guarantee that, in epidemiological terms, the effective reproduction number is less than unity. This condition has three advantages: (i) it is easily computable; (ii) it is directly related to the model parameters; (iii) it …
National responses to the Covid-19 pandemic varied markedly across countries, from business-as-usual to complete shutdowns. Policies aimed at disrupting the viral transmission cycle and preventing the healthcare system from being overwhelmed, simultaneously exact an economic toll. We developed a intervention policy model that comprised the relative human, economic and healthcare costs of non-pharmaceutical epidemic intervention and arrived at the optimal strategy using the neuroevolution algorithm. The proposed model finds the minimum required reduction in contact rates to maintain the burden …
Motivated by the increasing number of COVID-19 cases that have been observed in many countries after the vaccination and relaxation of non-pharmaceutical interventions, we propose a mathematical model on time-varying networks for the spread of recurrent epidemic diseases in a partially vaccinated population. The model encapsulates several realistic features, such as the different effectiveness of the vaccine against transmission and development of severe symptoms, testing practices, the possible implementation of non-pharmaceutical interventions to reduce the transmission, isolation of detecte…
Facing a global epidemic of new infectious diseases such as COVID-19, non-pharmaceutical interventions (NPIs), which reduce transmission rates without medical actions, are being implemented around the world to mitigate spreads. One of the problems in assessing the effects of NPIs is that different NPIs have been implemented at different times based on the situation of each country; therefore, few assumptions can be shared about how the introduction of policies affects the patient population. Mathematical models can contribute to further understanding these phenomena by obtaining analytical sol…
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…
We present modeling of the COVID-19 epidemic in Illinois, USA, capturing the implementation of a Stay-at-Home order and scenarios for its eventual release. We use a non-Markovian age-of-infection model that is capable of handling long and variable time delays without changing its model topology. Bayesian estimation of model parameters is carried out using Markov Chain Monte Carlo (MCMC) methods. This framework allows us to treat all available input information, including both the previously published parameters of the epidemic and available local data, in a uniform manner. To accurately model …
Mathematical models are instrumental to forecast the spread of pathogens and to evaluate the effectiveness of non-pharmaceutical measures. A plethora of optimal strategies has been recently developed to minimize either the infected peak prevalence (IPP) or the epidemic final size (EFS). While most of the control strategies optimize a simple cost function along a fixed finite-time horizon, no consensus has been reached about how to simultaneously handle the IPP, the EFS, and the avoiding of new cycles of infections rebounding. In this work, based on the characterization of the dynamical behavio…
Understanding how to effectively control an epidemic spreading on a network is a problem of paramount importance for the scientific community. The ongoing COVID-19 pandemic has highlighted the need for policies that mitigate the spread, without relying on pharmaceutical interventions, that is, without the medical assurance of the recovery process. These policies typically entail lockdowns and mobility restrictions, having thus nonnegligible socio-economic consequences for the population. In this paper, we focus on the problem of finding the optimum policies that "flatten the epidemic curve" wh…
Protecting interventions of many types (both pharmaceutical and non-pharmaceutical) can be deployed against the spreading of a communicable disease, as the worldwide COVID-19 pandemic has dramatically shown. Here we investigate in detail the effects at the population level of interventions that provide an asymmetric protection between the people involved in a single interaction. Masks of different filtration types, either protecting mainly the wearer or the contacts of the wearer, are a prominent example of these interventions. By means of analytical calculations and extensive simulations of s…
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 …
An Ebola outbreak of unparalleled size is currently affecting several countries in West Africa, and international efforts to control the outbreak are underway. However, the efficacy of these interventions, and their likely impact on an Ebola epidemic of this size, is unknown. Forecasting and simulation of these interventions may inform public health efforts. We use existing data from Liberia and Sierra Leone to parameterize a mathematical model of Ebola and use this model to forecast the progression of the epidemic, as well as the efficacy of several interventions, including increased contact …
Social distancing and lockdown are the two main non-pharmaceutical interventions being used by the UK government to contain and control the COVID-19 epidemic; these are being applied uniformly across the entire country, even though the results of the Imperial College report by Ferguson et al show that the impact of the infection increases sharply with age. This paper develops a variant of the workhorse SIR model for epidemics, where the population is classified into a number of age groups. This allows us to understand the effects of age-dependent controls on the epidemic, and explore possible …
The goal of this work is to consider widespread use of face masks as a non-pharmaceutical control strategy for the Covid-19 pandemic. A SEIR model that divides the population into individuals that wear masks and those that do not is considered. After calculating the basic reproductive number by a next generation approach, a criterion for determining when an epidemic can be prevented by the use of masks only and the critical percentage of mask users for disease prevention in the population are derived. The results are then applied to real world data from the United States, Brazil and Italy.
Investigating the effect of adaptive optimal control function in epidemic dynamics: predictions and strategy evolution based on SIR/V game theoretic framework
The spread of COVID-19 has been thwarted in most countries through non-pharmaceutical interventions. In particular, the most effective measures in this direction have been the stay-at-home and closure strategies of businesses and schools. However, population-wide lockdowns are far from being optimal carrying heavy economic consequences. Therefore, there is nowadays a strong interest in designing more efficient restrictions. In this work, starting from a recent kinetic-type model which takes into account the heterogeneity described by the social contact of individuals, we analyze the effects of…
A plethora of prediction models of SARS-CoV-2 pandemic were proposed in the past. Prediction performances not only depend on the structure and features of the model, but also on its parametrization. Official databases are often biased due to lag in reporting of cases, changing testing policy or incompleteness of data. Moreover, model parametrization is time-dependent e.g. due to changing age-structures, new emerging virus variants, non-pharmaceutical interventions and ongoing vaccination programs. To cover these aspects, we develop a principled approach to parametrize SIR-type epidemiologic mo…
Background: The impact of individual non-pharmaceutical interventions (NPI) such as state-wide stay-at-home orders, school closures and gathering size limitations, on the COVID-19 epidemic is unknown. Understanding the impact that above listed NPI have on disease transmission is critical for policy makers, particularly as case counts increase again in some areas. Methods: Using a Bayesian framework, we reconstructed the incidence and time-varying reproductive number (Rt) curves to investigate the relationship between Rt, individual mobility as measured by Google Community Mobility Reports, and…
Contact tracing and quarantine are well established non-pharmaceutical epidemic control tools. The paper aims to clarify the impact of these measures in COVID-19 epidemic. A new deterministic model is introduced (SEIRQ: susceptible, exposed, infectious, removed, quarantined) with Q compartment capturing individuals and releasing them with delay. We obtain a simple rule defining the reproduction number $\mathcal{R}$ in terms of quarantine parameters, ratio of diagnosed cases and transmission parameters. The model is applied to the epidemic in Poland in March - April 2020, when social distancing…
The pandemic caused by the novel Coronavirus SARS-CoV2 has been responsible for life threatening health complications, and extreme pressure on healthcare systems. While preventive and definite curative medical interventions are yet to arrive, Non-Pharmaceutical Interventions (NPIs) like physical isolation, quarantine and drastic social measures imposed by governing agencies are effective in arresting the spread of infections in a population. In densely populated countries like India, lockdown interventions are partially effective due to social and administrative complexities. Using detailed de…
Initial hopes of quickly eradicating the COVID-19 pandemic proved futile, and the goal shifted to controlling the peak of the infection, so as to minimize the load on healthcare systems. To that end, public health authorities intervened aggressively to institute social distancing, lock-down policies, and other Non-Pharmaceutical Interventions (NPIs). Given the high social, educational, psychological, and economic costs of NPIs, authorities tune them, alternatively tightening up or relaxing rules, with the result that, in effect, a relatively flat infection rate results. For example, during the…
In this work, we simulate the COVID-19 pandemic dynamics in a population modeled as a network of groups wherein infection can propagate both via intra-group and via inter-group interactions. Our results emphasize the importance of diminishing the inter-group infections in the effort of substantial flattening and delaying of the epi(demiologic) curve with concomitant mitigation of disastrous economy and social consequences. To exemplify with a limiting case, splitting a population into m (say, 5 or 10) noninteracting groups while keeping intra-group interaction unchanged yields a stretched epid…
Inria（法国国家信息与自动化研究所）；Univ. de Bordeaux（波尔多大学）；Inserm（法国国家健康与医学研究院）；GREThA UMR 5113（应用理论经济学研究实验室（UMR 5113））；ENSTA ParisTech（巴黎高等先进技术学院）
Epidemiologists model the dynamics of epidemics in order to propose control strategies based on pharmaceutical and non-pharmaceutical interventions (contact limitation, lock down, vaccination, etc). Hand-designing such strategies is not trivial because of the number of possible interventions and the difficulty to predict long-term effects. This task can be cast as an optimization problem where state-of-the-art machine learning algorithms such as deep reinforcement learning, might bring significant value. However, the specificity of each domain -- epidemic modelling or solving optimization prob…
The ongoing SARS-CoV-2 pandemic has been holding the world hostage for more than a year now. Mobility is key to viral spreading and its restriction is the main non-pharmaceutical interventions to fight the virus expansion. Previous works have shown a connection between the structural organization of cities and the movement patterns of their residents. This puts urban centers in the focus of epidemic surveillance and interventions. Here we show that the organization of urban flows has a tremendous impact on disease spreading and on the amenability of different mitigation strategies. By studying…
PyRoss is an open-source Python library that offers an integrated platform for inference, prediction and optimisation of NPIs in age- and contact-structured epidemiological compartment models. This report outlines the rationale and functionality of the PyRoss library, with various illustrations and examples focusing on well-mixed, age-structured populations. The PyRoss library supports arbitrary structured models formulated stochastically (as master equations) or deterministically (as ODEs) and allows mid-run transitioning from one to the other. By supporting additional compartmental subdivisi…
Some basic facts that enable or constrain efforts to "flatten the curve" by non-pharmaceutical interventions (NPI) are summarized and placed in the current context of the COVID-19 epidemic. Analytical formulas are presented for a simple two-tier NPI strategy that places different social distancing targets for high- and low-risk groups. The results aim to facilitate rapid what-if analysis rather than replace detailed simulation, which remains indispensable for informed decision making. The appearance of the oft neglected Lambert function in the resulting formulas is noted.
Following the emergence of a novel coronavirus (SARS-CoV-2) and its spread outside of China, Europe has experienced large epidemics. In response, many European countries have implemented unprecedented non-pharmaceutical interventions including case isolation, the closure of schools and universities, banning of mass gatherings and/or public events, and most recently, wide-scale social distancing including local and national lockdowns. In this technical update, we extend a semi-mechanistic Bayesian hierarchical model that infers the impact of these interventions and estimates the number of infec…
Controlling the spread of COVID-19 - even after a licensed vaccine is available - requires the effective use of non-pharmaceutical interventions: physical distancing, limits on group sizes, mask wearing, etc. To date, such interventions have neither been uniformly nor systematically implemented in most countries. For example, even when under strict stay-at-home orders, numerous jurisdictions granted exceptions and/or were in close proximity to locations with entirely different regulations in place. Here, we investigate the impact of such geographic inconsistencies in epidemic control policies …
Non-pharmaceutical measures such as social distancing, can play an important role to control an epidemic in the absence of vaccinations. In this paper, we study the impact of social distancing on epidemics for which it is executable. We use a mathematical model combining human mobility and disease spreading. For the mobility dynamics, we design an agent based model consisting of pedestrian dynamics with a novel type of force to resemble social distancing in crowded sites. For the spreading dynamics, we consider the compartmental SIE dynamics plus an indirect transmission with the footprints of…
In the context of SARS-CoV-2 pandemic, mathematical modelling has played a fundamental role for making forecasts, simulating scenarios and evaluating the impact of preventive political, social and pharmaceutical measures. Optimal control theory can be a useful tool based on solid mathematical bases to plan the vaccination campaign in the direction of eradicating the pandemic as fast as possible. The aim of this work is to explore the optimal prioritisation order for planning vaccination campaigns able to achieve specific goals, as the reduction of the amount of infected, deceased and hospitali…
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…
