ABSTRACT
In this work, we develop a model of the immune response to respiratory viral infections taking into account some particular properties of the SARS-CoV-2 infection. The model represents a system of ordinary differential equations for the concentrations of epithelial cells, immune cells, virus and inflammatory cytokines. Conventional analysis of the existence and stability of stationary points is completed by numerical simulations in order to study dynamics of solutions. Behavior of solutions is characterized by large peaks of virus concentration specific for acute respiratory viral infections. At the first stage, we study the innate immune response based on the protective properties of interferon secreted by virus-infected cells. On the other hand, viral infection down-regulates interferon production. Their competition can lead to the bistability of the system with different regimes of infection progression with high or low intensity. In the case of infection outbreak, the incubation period and the maximal viral load depend on the initial viral load and the parameters of the immune response. In particular, increase of the initial viral load leads to shorter incubation period and higher maximal viral load. In order to study the emergence and dynamics of cytokine storm, we consider proinflammatory cytokines produced by cells of the innate immune response. Depending on parameters of the model, the system can remain in the normal inflammatory state specific for viral infections or, due to positive feedback between inflammation and immune cells, pass to cytokine storm characterized by excessive production of proinflammatory cytokines. Furthermore, inflammatory cell death can stimulate transition to cytokine storm. However, it cannot sustain it by itself without the innate immune response. Assumptions of the model and obtained results are in qualitative agreement with the experimental and clinical data. © 2022 Maria Cristina Leon Atupana, Alexey A. Tokarev, Vitaly A. Volpert.
ABSTRACT
This study presents the results of treatment of 98 patients with risk of development of severe coronavirus disease (hereinafter COVID-19) with the first positive result of polymerase chain reaction test for SARS-CoV-2 in a day clinic of the multidisciplinary Z.A. Bashlyaeva Children’s Municipal Clinical Hospital. To prevent the clinical manifestation of COVID-19 and the progression of the main disease all these children were treated with virus-neutralizing monoclonal antibodies (sotrovimab 500 mg dissolved in 92 mL of 0.9% sodium chloride solution intravenously for 30 minutes, once, for children over 12 years old and with body weight over 12 kg;balanivimab 700 mg + etesivimab 1400 mg pre-dissolved in 250 mL of 0.9% sodium chloride solution intravenously for 30 minutes, once). Patients underwent a comprehensive clinical, laboratory and instrumental examination both initially and in dynamics for 3–7–11 days after therapy according to the developed clinical algorithm. The effectiveness of biological therapy in children with a risk of severe COVID-19 was noted in 100% of cases. None of the observed patients had either a clinical manifestation of COVID-19 or a relapse of the main chronic disease.
ABSTRACT
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.
ABSTRACT
Epidemiological data on seasonal influenza show that the growth rate of the number of infected individuals can increase passing from one exponential growth rate to another one with a larger exponent. Such behavior is not described by conventional epidemiological models. In this work an immuno-epidemiological model is proposed in order to describe this two-stage growth. It takes into account that the growth in the number of infected individuals increases the initial viral load and provides a passage from the first stage of epidemic where only people with weak immune response are infected to the second stage where people with strong immune response are also infected. This scenario may be viewed as an increase of the effective number of susceptible increasing the effective growth rate of infected. © The authors. Published by EDP Sciences, 2020.