Emergence and competition of virus variants in respiratory viral infections.

The emergence of new variants of concern (VOCs) of the SARS-CoV-2 infection is one of the main factors of epidemic progression. Their development can be characterized by three critical stages: virus mutation leading to the appearance of new viable variants; the competition of different variants leading to the production of a sufficiently large number of copies; and infection transmission between individuals and its spreading in the population. The first two stages take place at the individual level (infected individual), while the third one takes place at the population level with possible competition between different variants. This work is devoted to the mathematical modeling of the first two stages of this process: the emergence of new variants and their progression in the epithelial tissue with a possible competition between them. The emergence of new virus variants is modeled with non-local reaction-diffusion equations describing virus evolution and immune escape in the space of genotypes. The conditions of the emergence of new virus variants are determined by the mutation rate, the cross-reactivity of the immune response, and the rates of virus replication and death. Once different variants emerge, they spread in the infected tissue with a certain speed and viral load that can be determined through the parameters of the model. The competition of different variants for uninfected cells leads to the emergence of a single dominant variant and the elimination of the others due to competitive exclusion. The dominant variant is the one with the maximal individual spreading speed. Thus, the emergence of new variants at the individual level is determined by the immune escape and by the virus spreading speed in the infected tissue.

Mathematical modeling of respiratory viral infection and applications to SARS-CoV-2 progression.

Viral infection in cell culture and tissue is modeled with delay reaction-diffusion equations. It is shown that progression of viral infection can be characterized by the viral replication number, time-dependent viral load, and the speed of infection spreading. These three characteristics are determined through the original model parameters including the rates of cell infection and of virus production in the infected cells. The clinical manifestations of viral infection, depending on tissue damage, correlate with the speed of infection spreading, while the infectivity of a respiratory infection depends on the viral load in the upper respiratory tract. Parameter determination from the experiments on Delta and Omicron variants allows the estimation of the infection spreading speed and viral load. Different variants of the SARS-CoV-2 infection are compared confirming that Omicron is more infectious and has less severe symptoms than Delta variant. Within the same variant, spreading speed (symptoms) correlates with viral load allowing prognosis of disease progression.

Infection spreading in cell culture as a reaction-diffusion wave: RAIRO: Numerical Analysis

Infection spreading in cell culture occurs due to virus replication in infected cells and its random motion in the extracellular space. Multiplicity of infection experiments in cell cultures are conventionally used for the characterization of viral infection by the number of viral plaques and the rate of their growth. We describe this process with a delay reaction-diffusion system of equations for the concentrations of uninfected cells, infected cells, virus, and interferon. Time delay corresponds to the duration of viral replication inside infected cells. We show that infection propagates in cell culture as a reaction-diffusion wave, we determine the wave speed and prove its existence. Next, we carry out numerical simulations and identify three stages of infection progression: infection decay during time delay due to virus replication, explosive growth of viral load when infected cells begin to reproduce it, and finally, wave-like infection progression in cell culture characterized by a constant or slowly growing total viral load. The modelling results are in agreement with the experimental data for the coronavirus infection in a culture of epithelial cells and for some other experiments. The presence of interferon produced by infected cells decreases the viral load but does not change the speed of infection progression in cell culture. In the 2D modelling, the total viral load grows faster than in the 1D case due to the increase of plaque perimeter.

Virus replication and competition in a cell culture: Application to the SARS-CoV-2 variants.

Viral replication in a cell culture is described by a delay reaction-diffusion system. It is shown that infection spreads in cell culture as a reaction-diffusion wave, for which the speed of propagation and viral load can be determined both analytically and numerically. Competition of two virus variants in the same cell culture is studied, and it is shown that the variant with larger individual wave speed out-competes another one, and eliminates it. This approach is applied to the Delta and Omicron variants of the SARS-CoV-2 infection in the cultures of human epithelial and lung cells, allowing characterization of infectivity and virulence of each variant, and their comparison.

A DIFFUSIVE SEIR MODEL FOR COMMUNITY TRANSMISSION OF COVID-19 EPIDEMICS: APPLICATION TO BRAZIL

A mathematical model incorporating diffusion is developed to describe the spatial spread of COVID-19 epidemics in geographical regions. The dynamics of the spatial spread are based on community transmission of the virus. The model is applied to the outbreak of the COVID-19 epidemic in Brazil. © 2022 Mathematics in Applied Sciences and Engineering. All rights reserved.

Impulsive Reaction-Diffusion Delayed Models in Biology: Integral Manifolds Approach.

In this paper we study an impulsive delayed reaction-diffusion model applied in biology. The introduced model generalizes existing reaction-diffusion delayed epidemic models to the impulsive case. The integral manifolds notion has been introduced to the model under consideration. This notion extends the single state notion and has important applications in the study of multi-stable systems. By means of an extension of the Lyapunov method integral manifolds' existence, results are established. Based on the Lyapunov functions technique combined with a Poincarè-type inequality qualitative criteria related to boundedness, permanence, and stability of the integral manifolds are also presented. The application of the proposed impulsive control model is closely related to a most important problems in the mathematical biology-the problem of optimal control of epidemic models. The considered impulsive effects can be used by epidemiologists as a very effective therapy control strategy. In addition, since the integral manifolds approach is relevant in various contexts, our results can be applied in the qualitative investigations of many problems in the epidemiology of diverse interest.

CONTROLLED SINGULAR EVOLUTION EQUATIONS AND PONTRYAGIN TYPE MAXIMUM PRINCIPLE WITH APPLICATIONS

Due to the propagation of new coronavirus (COVID-19) on the community, global researchers are concerned with how to minimize the impact of COVID-19 on the world. Mathematical models are effective tools that help to prevent and control this disease. This paper mainly focuses on the optimal control problems of an epidemic system governed by a class of singular evolution equations. The mild solutions of such equations of RiemannLiouville or Caputo types are special cases of the proposed equations. We firstly discuss well-posedness in an appropriate functional space for such equations. In order to reduce the cost caused by control process and vaccines, and minimize the total number of susceptible people and infected people as much as possible, an optimal control problem of an epidemic system is presented.