Control Strategies for COVID-19 Epidemic with Vaccination, Shield Immunity and Quarantine: A Metric Temporal Logic Approach

Ever since the outbreak of the COVID-19 epidemic, various public health control strategies have been proposed and tested against the coronavirus SARS-CoV-2. We study three specific COVID-19 epidemic control models: the susceptible, exposed, infectious, recovered (SEIR) model with vaccination control; the SEIR model with shield immunity control; and the susceptible, un-quarantined infected, quarantined infected, confirmed infected (SUQC) model with quarantine control. We express the control requirement in metric temporal logic (MTL) formulas (a type of formal specification languages) which can specify the expected control outcomes such as "the deaths from the infection should never exceed one thousand per day within the next three months" or "the population immune from the disease should eventually exceed 200 thousand within the next 100 to 120 days". We then develop methods for synthesizing control strategies with MTL specifications. To the best of our knowledge, this is the first paper to systematically synthesize control strategies based on the COVID-19 epidemic models with formal specifications. We provide simulation results in three different case studies: vaccination control for the COVID-19 epidemic with model parameters estimated from data in Lombardy, Italy; shield immunity control for the COVID-19 epidemic with model parameters estimated from data in Lombardy, Italy; and quarantine control for the COVID-19 epidemic with model parameters estimated from data in Wuhan, China. The results show that the proposed synthesis approach can generate control inputs such that the time-varying numbers of individuals in each category (e.g., infectious, immune) satisfy the MTL specifications. The results also show that early intervention is essential in mitigating the spread of COVID-19, and more control effort is needed for more stringent MTL specifications

On a Controlled Se(Is)(Ih)(Iicu)AR Epidemic Model with Output Controllability Issues to Satisfy Hospital Constraints on Hospitalized Patients

An epidemic model, the so-called SE(Is)(Ih)(Iicu)AR epidemic model, is proposed which splits the infectious subpopulation of the classical SEIR (Susceptible-Exposed-Infectious-Recovered) model into four subpopulations, namely asymptomatic infectious and three categories of symptomatic infectious, namely slight infectious, non-intensive care infectious, and intensive care hospitalized infectious. The exposed subpopulation has four different transitions to each one of the four kinds of infectious subpopulations governed under eventually different proportionality parameters. The performed research relies on the problem of satisfying prescribed hospitalization constraints related to the number of patients via control interventions. There are four potential available controls which can be manipulated, namely the vaccination of the susceptible individuals, the treatment of the non-intensive care unit hospitalized patients, the treatment of the hospitalized patients at the intensive care unit, and the transmission rate which can be eventually updated via public interventions such as isolation of the infectious, rules of groups meetings, use of face masks, decrees of partial or total quarantines, and others. The patients staying at the non-intensive care unit and those staying at the intensive care unit are eventually, but not necessarily, managed as two different hospitalized subpopulations. The controls are designed based on output controllability issues in the sense that the levels of hospital admissions are constrained via prescribed maximum levels and the measurable outputs are defined by the hospitalized patients either under a joint consideration of the sum of both subpopulations or separately. In this second case, it is possible to target any of the two hospitalized subpopulations only or both of them considered as two different components of the output. Different algorithms are given to design the controls which guarantee, if possible, that the prescribed hospitalization constraints hold. If this were not possible, because the levels of serious infection are too high according to the hospital availability means, then the constraints are revised and modified accordingly so that the amended ones could be satisfied by a set of controls. The algorithms are tested through numerically worked examples under disease parameterizations of COVID-19.This research received funding from the Spanish Institute of Health Carlos III through Grant COV 20/01213, the Spanish Government and the European Commission through Grant RTI2018-094336-B-I00 (MCIU/AEI/FEDER, UE) and the Basque Government for Grant IT1207-19

Model Predictive Control Tailored to Epidemic Models

We propose a model predictive control (MPC) approach for minimising the social distancing and quarantine measures during a pandemic while maintaining a hard infection cap. To this end, we study the admissible and the maximal robust positively invariant set (MRPI) of the standard SEIR compartmental model with control inputs. Exploiting the fact that in the MRPI all restrictions can be lifted without violating the infection cap, we choose a suitable subset of the MRPI to define terminal constraints in our MPC routine and show that the number of infected people decays exponentially within this set. Furthermore, under mild assumptions we prove existence of a uniform bound on the time required to reach this terminal region (without violating the infection cap) starting in the admissible set. The findings are substantiated based on a numerical case study.Comment: 14 pages, 3 figure

Social Contact Networks and Disease Eradicability under Voluntary Vaccination

Certain theories suggest that it should be difficult or impossible to eradicate a vaccine-preventable disease under voluntary vaccination: Herd immunity implies that the individual incentive to vaccinate disappears at high coverage levels. Historically, there have been examples of declining coverage for vaccines, such as MMR vaccine and whole-cell pertussis vaccine, that are consistent with this theory. On the other hand, smallpox was globally eradicated by 1980 despite voluntary vaccination policies in many jurisdictions. Previous modeling studies of the interplay between disease dynamics and individual vaccinating behavior have assumed that infection is transmitted in a homogeneously mixing population. By comparison, here we simulate transmission of a vaccine-preventable SEIR infection through a random, static contact network. Individuals choose whether to vaccinate based on infection risks from neighbors, and based on vaccine risks. When neighborhood size is small, rational vaccinating behavior results in rapid containment of the infection through voluntary ring vaccination. As neighborhood size increases (while the average force of infection is held constant), a threshold is reached beyond which the infection can break through partially vaccinated rings, percolating through the whole population and resulting in considerable epidemic final sizes and a large number vaccinated. The former outcome represents convergence between individually and socially optimal outcomes, whereas the latter represents their divergence, as observed in most models of individual vaccinating behavior that assume homogeneous mixing. Similar effects are observed in an extended model using smallpox-specific natural history and transmissibility assumptions. This work illustrates the significant qualitative differences between behavior–infection dynamics in discrete contact-structured populations versus continuous unstructured populations. This work also shows how disease eradicability in populations where voluntary vaccination is the primary control mechanism may depend partly on whether the disease is transmissible only to a few close social contacts or to a larger subset of the population

Reliable optimal controls for SEIR models in epidemiology

We present and compare two different optimal control approaches applied to SEIR models in epidemiology, which allow us to obtain some policies for controlling the spread of an epidemic. The first approach uses Dynamic Programming to characterise the value function of the problem as the solution of a partial differential equation, the Hamilton-Jacobi-Bellman equation, and derive the optimal policy in feedback form. The second is based on Pontryagin's maximum principle and directly gives open-loop controls, via the solution of an optimality system of ordinary differential equations. This method, however, may not converge to the optimal solution. We propose a combination of the two methods in order to obtain high-quality and reliable solutions. Several simulations are presented and discussed

Sensitivity analysis and optimal treatment control for a mathematical model of human papillomavirus infection

Human papillomavirus (HPV) is one of the most common sexually transmitted viruses, and is a causal agent of cervical cancer. We aimed to develop a mathematical model of HPV natural history and qualitatively analyzed the stability of disease-free equilibrium, non-existence of limit cycle and existence of forward bifurcation. We performed sensitivity analysis to identify key epidemiological parameters. The Partial Rank Correlation Coefficient (PRCC) values for basic reproduction number shows that controlling contact rate plays an important role in disturbing equilibrium of HPV infection. Moreover, the increase of medical level is the most effective measure to prevent new HPV infections. Optimal treatment problem is solved and theoretical analysis is verified by numerical simulation

Mathematical control of complex systems 2013

Mathematical control of complex systems have already become an ideal research area for control engineers, mathematicians, computer scientists, and biologists to understand, manage, analyze, and interpret functional information/dynamical behaviours from real-world complex dynamical systems, such as communication systems, process control, environmental systems, intelligent manufacturing systems, transportation systems, and structural systems. This special issue aims to bring together the latest/innovative knowledge and advances in mathematics for handling complex systems. Topics include, but are not limited to the following: control systems theory (behavioural systems, networked control systems, delay systems, distributed systems, infinite-dimensional systems, and positive systems); networked control (channel capacity constraints, control over communication networks, distributed filtering and control, information theory and control, and sensor networks); and stochastic systems (nonlinear filtering, nonparametric methods, particle filtering, partial identification, stochastic control, stochastic realization, system identification)