Complex network model for COVID-19: Human behavior, pseudo-periodic solutions and multiple epidemic waves.

We propose a mathematical model for the transmission dynamics of SARS-CoV-2 in a homogeneously mixing non constant population, and generalize it to a model where the parameters are given by piecewise constant functions. This allows us to model the human behavior and the impact of public health policies on the dynamics of the curve of active infected individuals during a COVID-19 epidemic outbreak. After proving the existence and global asymptotic stability of the disease-free and endemic equilibrium points of the model with constant parameters, we consider a family of Cauchy problems, with piecewise constant parameters, and prove the existence of pseudo-oscillations between a neighborhood of the disease-free equilibrium and a neighborhood of the endemic equilibrium, in a biologically feasible region. In the context of the COVID-19 pandemic, this pseudo-periodic solutions are related to the emergence of epidemic waves. Then, to capture the impact of mobility in the dynamics of COVID-19 epidemics, we propose a complex network with six distinct regions based on COVID-19 real data from Portugal. We perform numerical simulations for the complex network model, where the objective is to determine a topology that minimizes the level of active infected individuals and the existence of topologies that are likely to worsen the level of infection. We claim that this methodology is a tool with enormous potential in the current pandemic context, and can be applied in the management of outbreaks (in regional terms) but also to manage the opening/closing of borders.

Model-free based control of a HIV/AIDS prevention model.

Controlling an epidemiological model is often performed using optimal control theory techniques for which the solution depends on the equations of the controlled system, objective functional and possible state and/or control constraints. In this paper, we propose a model-free control approach based on an algorithm that operates in 'real-time' and drives the state solution according to a direct feedback on the state solution that is aimed to be minimized, and without knowing explicitly the equations of the controlled system. We consider a concrete epidemic problem of minimizing the number of HIV infected individuals, through the preventive measure pre-exposure prophylaxis (PrEP) given to susceptible individuals. The solutions must satisfy control and mixed state-control constraints that represent the limitations on PrEP implementation. Our model-free based control algorithm allows to close the loop between the number of infected individuals with HIV and the supply of PrEP medication 'in real time', in such a manner that the number of infected individuals is asymptotically reduced and the number of individuals under PrEP medication remains below a fixed constant value. We prove the efficiency of our approach and compare the model-free control solutions with the ones obtained using a classical optimal control approach via Pontryagin maximum principle. The performed numerical simulations allow us to conclude that the model-free based control strategy highlights new and interesting performances compared with the classical optimal control approach.

Analysis of a COVID-19 compartmental model: a mathematical and computational approach.

In this note, we consider a compartmental epidemic mathematical model given by a system of differential equations. We provide a complete toolkit for performing both a symbolic and numerical analysis of the spreading of COVID-19. By using the free and open-source programming language Python and the mathematical software SageMath, we contribute for the reproducibility of the mathematical analysis of the stability of the equilibrium points of epidemic models and their fitting to real data. The mathematical tools and codes can be adapted to a wide range of mathematical epidemic models.

Fractional model of COVID-19 applied to Galicia, Spain and Portugal.

A fractional compartmental mathematical model for the spread of the COVID-19 disease is proposed. Special focus has been done on the transmissibility of super-spreaders individuals. Numerical simulations are shown for data of Galicia, Spain, and Portugal. For each region, the order of the Caputo derivative takes a different value, that is not close to one, showing the relevance of considering fractional models.

Optimal control of the COVID-19 pandemic: controlled sanitary deconfinement in Portugal.

The COVID-19 pandemic has forced policy makers to decree urgent confinements to stop a rapid and massive contagion. However, after that stage, societies are being forced to find an equilibrium between the need to reduce contagion rates and the need to reopen their economies. The experience hitherto lived has provided data on the evolution of the pandemic, in particular the population dynamics as a result of the public health measures enacted. This allows the formulation of forecasting mathematical models to anticipate the consequences of political decisions. Here we propose a model to do so and apply it to the case of Portugal. With a mathematical deterministic model, described by a system of ordinary differential equations, we fit the real evolution of COVID-19 in this country. After identification of the population readiness to follow social restrictions, by analyzing the social media, we incorporate this effect in a version of the model that allow us to check different scenarios. This is realized by considering a Monte Carlo discrete version of the previous model coupled via a complex network. Then, we apply optimal control theory to maximize the number of people returning to "normal life" and minimizing the number of active infected individuals with minimal economical costs while warranting a low level of hospitalizations. This work allows testing various scenarios of pandemic management (closure of sectors of the economy, partial/total compliance with protection measures by citizens, number of beds in intensive care units, etc.), ensuring the responsiveness of the health system, thus being a public health decision support tool.

Optimal control of a tuberculosis model with state and control delays.

We introduce delays in a tuberculosis (TB) model, representing the time delay on the diagnosis and commencement of treatment of individuals with active TB infection. The stability of the disease free and endemic equilibriums is investigated for any time delay. Corresponding optimal control problems, with time delays in both state and control variables, are formulated and studied. Although it is well-known that there is a delay between two to eight weeks between TB infection and reaction of body's immune system to tuberculin, delays for the active infected to be detected and treated, and delays on the treatment of persistent latent individuals due to clinical and patient reasons, which clearly justifies the introduction of time delays on state and control measures, our work seems to be the first to consider such time-delays for TB and apply time-delay optimal control to carry out the optimality analysis.

Cost-effectiveness analysis of optimal control measures for tuberculosis.

We propose and analyze an optimal control problem where the control system is a mathematical model for tuberculosis that considers reinfection. The control functions represent the fraction of early latent and persistent latent individuals that are treated. Our aim was to study how these control measures should be implemented, for a certain time period, in order to reduce the number of active infected individuals, while minimizing the interventions implementation costs. The optimal intervention is compared along different epidemiological scenarios, by varying the transmission coefficient. The impact of variation of the risk of reinfection, as a result of acquired immunity to a previous infection for treated individuals on the optimal controls and associated solutions, is analyzed. A cost-effectiveness analysis is done, to compare the application of each one of the control measures, separately or in combination.

Optimal control for a tuberculosis model with reinfection and post-exposure interventions.

We apply optimal control theory to a tuberculosis model given by a system of ordinary differential equations. Optimal control strategies are proposed to minimize the cost of interventions, considering reinfection and post-exposure interventions. They depend on the parameters of the model and reduce effectively the number of active infectious and persistent latent individuals. The time that the optimal controls are at the upper bound increase with the transmission coefficient. A general explicit expression for the basic reproduction number is obtained and its sensitivity with respect to the model parameters is discussed. Numerical results show the usefulness of the optimization strategies.