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带隐现阶段和抗体免疫的 IAV/SARS-CoV-2 共感染模型的全球动力学

Global dynamics of IAV/SARS-CoV-2 coinfection model with eclipse phase and antibody immunity.

机构信息

Department of Mathematics, Faculty of Science, King Abdulaziz University, P. O. Box 80203, Jeddah 21589, Saudi Arabia.

出版信息

Math Biosci Eng. 2023 Jan;20(2):3873-3917. doi: 10.3934/mbe.2023182. Epub 2022 Dec 13.

Abstract

Coronavirus disease 2019 (COVID-19) and influenza are two respiratory infectious diseases of high importance widely studied around the world. COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while influenza is caused by one of the influenza viruses, A, B, C, and D. Influenza A virus (IAV) can infect a wide range of species. Studies have reported several cases of respiratory virus coinfection in hospitalized patients. IAV mimics the SARS-CoV-2 with respect to the seasonal occurrence, transmission routes, clinical manifestations and related immune responses. The present paper aimed to develop and investigate a mathematical model to study the within-host dynamics of IAV/SARS-CoV-2 coinfection with the eclipse (or latent) phase. The eclipse phase is the period of time that elapses between the viral entry into the target cell and the release of virions produced by that newly infected cell. The role of the immune system in controlling and clearing the coinfection is modeled. The model simulates the interaction between nine compartments, uninfected epithelial cells, latent/active SARS-CoV-2-infected cells, latent/active IAV-infected cells, free SARS-CoV-2 particles, free IAV particles, SARS-CoV-2-specific antibodies and IAV-specific antibodies. The regrowth and death of the uninfected epithelial cells are considered. We study the basic qualitative properties of the model, calculate all equilibria, and prove the global stability of all equilibria. The global stability of equilibria is established using the Lyapunov method. The theoretical findings are demonstrated via numerical simulations. The importance of considering the antibody immunity in the coinfection dynamics model is discussed. It is found that without modeling the antibody immunity, the case of IAV and SARS-CoV-2 coexistence will not occur. Further, we discuss the effect of IAV infection on the dynamics of SARS-CoV-2 single infection and vice versa.

摘要

新型冠状病毒肺炎(COVID-19)和流感是两种具有高度重要性的呼吸道传染病,在全球范围内得到了广泛研究。COVID-19 是由严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)引起的,而流感是由流感病毒 A、B、C 和 D 中的一种引起的。甲型流感病毒(IAV)可以感染广泛的物种。研究报告了几例住院患者呼吸道病毒合并感染的病例。IAV 在季节性发生、传播途径、临床表现和相关免疫反应方面与 SARS-CoV-2 相似。本文旨在开发和研究一个数学模型,以研究 IAV/SARS-CoV-2 合并感染的体内动力学,其中包括潜伏期。潜伏期是指病毒进入靶细胞到新感染细胞释放病毒颗粒之间的时间间隔。模型模拟了免疫系统在控制和清除合并感染中的作用。该模型模拟了九个隔室之间的相互作用,包括未感染的上皮细胞、潜伏/活跃的 SARS-CoV-2 感染细胞、潜伏/活跃的 IAV 感染细胞、游离的 SARS-CoV-2 颗粒、游离的 IAV 颗粒、SARS-CoV-2 特异性抗体和 IAV 特异性抗体。还考虑了未感染上皮细胞的再生和死亡。我们研究了模型的基本定性性质,计算了所有平衡点,并证明了所有平衡点的全局稳定性。平衡点的全局稳定性是通过李雅普诺夫方法建立的。理论结果通过数值模拟得到验证。讨论了在合并感染动力学模型中考虑抗体免疫的重要性。结果表明,如果不模拟抗体免疫,IAV 和 SARS-CoV-2 共存的情况就不会发生。此外,我们还讨论了 IAV 感染对 SARS-CoV-2 单感染动力学的影响,反之亦然。

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