Open accessJournal Article

Age-structured non-pharmaceutical interventions for optimal control of COVID-19 epidemic.

04 Mar 2021-PLOS Computational Biology (PLoS Comput Biol)-Vol. 17, Iss: 3
Abstract: In an epidemic, individuals can widely differ in the way they spread the infection depending on their age or on the number of days they have been infected for. In the absence of pharmaceutical interventions such as a vaccine or treatment, non-pharmaceutical interventions (e.g. physical or social distancing) are essential to mitigate the pandemic. We develop an original approach to identify the optimal age-stratified control strategy to implement as a function of the time since the onset of the epidemic. This is based on a model with a double continuous structure in terms of host age and time since infection. By applying optimal control theory to this model, we identify a solution that minimizes deaths and costs associated with the implementation of the control strategy itself. We also implement this strategy for three countries with contrasted age distributions (Burkina-Faso, France, and Vietnam). Overall, the optimal strategy varies throughout the epidemic, with a more intense control early on, and depending on host age, with a stronger control for the older population, except in the scenario where the cost associated with the control is low. In the latter scenario, we find strong differences across countries because the control extends to the younger population for France and Vietnam 2 to 3 months after the onset of the epidemic, but not for Burkina Faso. Finally, we show that the optimal control strategy strongly outperforms a constant uniform control exerted over the whole population or over its younger fraction. This improved understanding of the effect of age-based control interventions opens new perspectives for the field, especially for age-based contact tracing.

Topics: Population (54%)
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17 results found

Open accessJournal Article
Abstract: 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.

Topics: Optimal control (52%)

50 Citations

Open accessJournal Article
Abstract: We propose a model for the COVID-19 epidemic where the population is partitioned into classes corresponding to ages (that remain constant during the epidemic). The main feature is to take into account the infection age of the infected population. This allows to better simulate the infection propagation that crucially depend on the infection age. We discuss how to estimate the coefficients from data available in the future, and introduce a confinement variable as control. The cost function is a compromise between a confinement term, the hospitalization peak and the death toll. Our numerical experiments allow to evaluate the interest of confinement varying with age classes.

Topics: Population (54%)

12 Citations

Open accessPosted Content
Sara Grundel1, Stefan Heyder2, Thomas Hotz2, Tobias Ritschel1  +2 moreInstitutions (2)
Abstract: In this paper, we provide insights on how much testing and social distancing is required to control COVID-19. To this end, we develop a compartmental model that accounts for key aspects of the disease: 1) incubation time, 2) age-dependent symptom severity, and 3) testing and hospitalization delays; the model's parameters are chosen based on medical evidence, and, for concreteness, adapted to the German situation. Then, optimal mass-testing and age-dependent social-distancing policies are determined by solving optimal control problems both in open loop and within a model predictive control framework. We aim to minimize testing and/or social distancing until herd immunity sets in under a constraint on the number of available intensive care units. We find that an early and short lockdown is inevitable but can be slowly relaxed over the following months.

Topics: Intensive care (55%)

7 Citations

Open accessPosted Content
31 Aug 2020-medRxiv
Abstract: Background If SARS-CoV-2 elimination is not feasible, strategies are needed to minimise the impact of COVID-19 in the medium-to-long term, until safe and effective vaccines can be used at the population-level. Methods Using a mathematical model, we identified contact mitigation strategies that minimised COVID-19-related deaths or years of life lost (YLLs) over a time-horizon of 15 months, using an intervention lasting six or 12 months, in Belgium, France, Italy, Spain, Sweden and the UK. We used strategies that either altered age- or location-specific contact patterns. The optimisation was performed under the constraint that herd immunity should be achieved by the end of the intervention period if post-infection immunity was persistent. We then tested the effect of waning immunity on the strategies. Findings Strategies of contact mitigation by age were much more effective than those based on mitigation by location. Extremely stringent contact reductions for individuals aged over 50 were required in most countries to minimise deaths or YLLs. The median final proportion of the population ever-infected with SARS-CoV-2 after herd immunity was reached ranged between 30% and 43%, depending on the country and intervention duration. Compared to an unmitigated scenario, optimised age-specific mitigation was predicted to avert over 1 million deaths across the six countries. The optimised scenarios assuming persistent immunity resulted in comparable hospital occupancies to that experienced during the March-April European wave. However, if immunity was shortlived, high burdens were expected without permanent contact mitigation. Interpretation Our analysis suggests that age-selective mitigation strategies can reduce the mortality impacts of COVID-19 dramatically even when significant transmission occurs. The stringency of the required restrictions in some groups raises concerns about the practicality of these strategies. If post-infection immunity was short-lived, solutions based on a mitigation period designed to increase population immunity should be accompanied with ongoing contact mitigation to prevent large epidemic resurgence.

Topics: Population (52%)

6 Citations

Open accessJournal Article
Abstract: Malaria is one of the most common mosquito-borne diseases widespread in tropical and subtropical regions, causing thousands of deaths every year in the world. Few models considering a multiple structure model formulation including (i) the chronological age of human and mosquito populations, (ii) the time since they are infected, and (iii) humans waning immunity (i.e. the progressive loss of protective antibodies after recovery) have been developed. In this paper we formulate an age-structured model containing three structural variables. Using the integrated semigroups theory, we first handle the well-posedness of the model proposed. We also investigate the existence of steady-states. A disease-free equilibrium always exists while the existence of endemic equilibria is discussed. We derive the basic reproduction number R 0 which expression highlights the effect of the above structural variables on key important epidemiological traits of the human-vector association such as vectorial capacity (i.e., vector daily reproduction rate), humans transmission probability, and survival rate. The expression of R 0 obtained here generalizes the classical formula of the basic reproduction number. Next, we derive a necessary and sufficient condition that implies the bifurcation of an endemic equilibrium. In the specific case where the age-structure of the human population is neglected, we show that a bifurcation, either backward of forward, may occur at R 0 = 1 leading to the existence, or not, of multiple endemic equilibrium when 0 ≪ R 0 1 . Finally, the latter theoretical results are enlightened by numerical simulations.

Topics: Basic reproduction number (56.99%), Population (53%)

5 Citations

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Open accessJournal Article
Fei Zhou1, Ting Yu, Ronghui Du, Guohui Fan2  +16 moreInstitutions (5)
28 Mar 2020-The Lancet
Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

15,279 Citations

Open accessJournal Article
Qun Li1, Xuhua Guan1, Peng Wu2, Xiaoye Wang1  +43 moreInstitutions (6)
Abstract: Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the...

Topics: Coronavirus (54%)

10,234 Citations

Open accessBook
11 Jul 1991-
Abstract: Part 1 Microparasites: biology of host-microparasite associations the basic model - statics static aspects of eradication and control the basic model - dynamics dynamic aspects of eradication and control beyond the basic model - empirical evidence of inhomogeneous mixing age-related transmission rates genetic heterogeneity social heterogeneity and sexually transmitted diseases spatial and other kinds of heterogeneity endemic infections in developing countries indirectly transmitted microparasites. Part 2 Macroparasites: biology of host-macroparasite associations the basic model - statics the basic model - dynamics acquired immunity heterogeneity within the human community indirectly transmitted helminths experimental epidemiology parasites, genetic variability, and drug resistance the ecology and genetics of host-parasite associations.

7,668 Citations

Open accessJournal Article
Abstract: (1) One of the most striking features in the study of epidemics is the difficulty of finding a causal factor which appears to be adequate to account for the magnitude of the frequent epidemics of disease which visit almost every population. It was with a view to obtaining more insight regarding the effects of the various factors which govern the spread of contagious epidemics that the present investigation was undertaken. Reference may here be made to the work of Ross and Hudson (1915-17) in which the same problem is attacked. The problem is here carried to a further stage, and it is considered from a point of view which is in one sense more general. The problem may be summarised as follows: One (or more) infected person is introduced into a community of individuals, more or less susceptible to the disease in question. The disease spreads from the affected to the unaffected by contact infection. Each infected person runs through the course of his sickness, and finally is removed from the number of those who are sick, by recovery or by death. The chances of recovery or death vary from day to day during the course of his illness. The chances that the affected may convey infection to the unaffected are likewise dependent upon the stage of the sickness. As the epidemic spreads, the number of unaffected members of the community becomes reduced. Since the course of an epidemic is short compared with the life of an individual, the population may be considered as remaining constant, except in as far as it is modified by deaths due to the epidemic disease itself. In the course of time the epidemic may come to an end. One of the most important probems in epidemiology is to ascertain whether this termination occurs only when no susceptible individuals are left, or whether the interplay of the various factors of infectivity, recovery and mortality, may result in termination, whilst many susceptible individuals are still present in the unaffected population. It is difficult to treat this problem in its most general aspect. In the present communication discussion will be limited to the case in which all members of the community are initially equally susceptible to the disease, and it will be further assumed that complete immunity is conferred by a single infection.

7,409 Citations

Journal Article
01 Dec 2000-Siam Review
Abstract: Many models for the spread of infectious diseases in populations have been analyzed mathematically and applied to specific diseases. Threshold theorems involving the basic reproduction number $R_{0}$, the contact number $\sigma$, and the replacement number $R$ are reviewed for the classic SIR epidemic and endemic models. Similar results with new expressions for $R_{0}$ are obtained for MSEIR and SEIR endemic models with either continuous age or age groups. Values of $R_{0}$ and $\sigma$ are estimated for various diseases including measles in Niger and pertussis in the United States. Previous models with age structure, heterogeneity, and spatial structure are surveyed.