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A hybrid discrete-continuum model of immune responses to SARS-CoV-2 infection in the lung alveolar region, with a focus on interferon induced innate response
We develop a lattice-based, hybrid discrete-continuum modeling framework for SARS-CoV-2 exposure and infection in the human lung alveolar region, or parenchyma, the massive surface area for gas exchange. COVID-19 pneumonia is alveolar infection by the SARS-CoV-2 virus significant enough to compromis...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Ltd.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9533651/ https://www.ncbi.nlm.nih.gov/pubmed/36208668 http://dx.doi.org/10.1016/j.jtbi.2022.111293 |
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author | Aristotelous, Andreas C. Chen, Alex Forest, M. Gregory |
author_facet | Aristotelous, Andreas C. Chen, Alex Forest, M. Gregory |
author_sort | Aristotelous, Andreas C. |
collection | PubMed |
description | We develop a lattice-based, hybrid discrete-continuum modeling framework for SARS-CoV-2 exposure and infection in the human lung alveolar region, or parenchyma, the massive surface area for gas exchange. COVID-19 pneumonia is alveolar infection by the SARS-CoV-2 virus significant enough to compromise gas exchange. The modeling framework orchestrates the onset and progression of alveolar infection, spatially and temporally, beginning with a pre-immunity baseline, upon which we superimpose multiple mechanisms of immune protection conveyed by interferons and antibodies. The modeling framework is tunable to individual profiles, focusing here on degrees of innate immunity, and to the evolving infection–replication properties of SARS-CoV-2 variant strains. The model employs partial differential equations for virion, interferon, and antibody concentrations governed by diffusion in the thin fluid coating of alveolar cells, species and lattice interactions corresponding to sources and sinks for each species, and multiple immune protections signaled by interferons. The spatial domain is a two-dimensional, rectangular lattice of alveolar type I (non-infectable) and type II (infectable) cells with a stochastic, species-concentration-governed, switching dynamics of type II lattice sites from healthy to infected. Once infected, type II cells evolve through three phases: an eclipse phase during which RNA copies (virions) are assembled; a shedding phase during which virions and interferons are released; and then cell death. Model simulations yield the dynamic spread of, and immune protection against, alveolar infection and viral load from initial sites of exposure. We focus in this paper on model illustrations of the diversity of outcomes possible from alveolar infection, first absent of immune protection, and then with varying degrees of four known mechanisms of interferon-induced innate immune protection. We defer model illustrations of antibody protection to future studies. Results presented reinforce previous recognition that interferons produced solely by infected cells are insufficient to maintain a high efficacy level of immune protection, compelling additional mechanisms to clear alveolar infection, such as interferon production by immune cells and adaptive immunity (e.g., T cells). This manuscript was submitted as part of a theme issue on “Modelling COVID-19 and Preparedness for Future Pandemics”. |
format | Online Article Text |
id | pubmed-9533651 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95336512022-10-05 A hybrid discrete-continuum model of immune responses to SARS-CoV-2 infection in the lung alveolar region, with a focus on interferon induced innate response Aristotelous, Andreas C. Chen, Alex Forest, M. Gregory J Theor Biol Article We develop a lattice-based, hybrid discrete-continuum modeling framework for SARS-CoV-2 exposure and infection in the human lung alveolar region, or parenchyma, the massive surface area for gas exchange. COVID-19 pneumonia is alveolar infection by the SARS-CoV-2 virus significant enough to compromise gas exchange. The modeling framework orchestrates the onset and progression of alveolar infection, spatially and temporally, beginning with a pre-immunity baseline, upon which we superimpose multiple mechanisms of immune protection conveyed by interferons and antibodies. The modeling framework is tunable to individual profiles, focusing here on degrees of innate immunity, and to the evolving infection–replication properties of SARS-CoV-2 variant strains. The model employs partial differential equations for virion, interferon, and antibody concentrations governed by diffusion in the thin fluid coating of alveolar cells, species and lattice interactions corresponding to sources and sinks for each species, and multiple immune protections signaled by interferons. The spatial domain is a two-dimensional, rectangular lattice of alveolar type I (non-infectable) and type II (infectable) cells with a stochastic, species-concentration-governed, switching dynamics of type II lattice sites from healthy to infected. Once infected, type II cells evolve through three phases: an eclipse phase during which RNA copies (virions) are assembled; a shedding phase during which virions and interferons are released; and then cell death. Model simulations yield the dynamic spread of, and immune protection against, alveolar infection and viral load from initial sites of exposure. We focus in this paper on model illustrations of the diversity of outcomes possible from alveolar infection, first absent of immune protection, and then with varying degrees of four known mechanisms of interferon-induced innate immune protection. We defer model illustrations of antibody protection to future studies. Results presented reinforce previous recognition that interferons produced solely by infected cells are insufficient to maintain a high efficacy level of immune protection, compelling additional mechanisms to clear alveolar infection, such as interferon production by immune cells and adaptive immunity (e.g., T cells). This manuscript was submitted as part of a theme issue on “Modelling COVID-19 and Preparedness for Future Pandemics”. Elsevier Ltd. 2022-12-21 2022-10-05 /pmc/articles/PMC9533651/ /pubmed/36208668 http://dx.doi.org/10.1016/j.jtbi.2022.111293 Text en © 2022 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Aristotelous, Andreas C. Chen, Alex Forest, M. Gregory A hybrid discrete-continuum model of immune responses to SARS-CoV-2 infection in the lung alveolar region, with a focus on interferon induced innate response |
title | A hybrid discrete-continuum model of immune responses to SARS-CoV-2 infection in the lung alveolar region, with a focus on interferon induced innate response |
title_full | A hybrid discrete-continuum model of immune responses to SARS-CoV-2 infection in the lung alveolar region, with a focus on interferon induced innate response |
title_fullStr | A hybrid discrete-continuum model of immune responses to SARS-CoV-2 infection in the lung alveolar region, with a focus on interferon induced innate response |
title_full_unstemmed | A hybrid discrete-continuum model of immune responses to SARS-CoV-2 infection in the lung alveolar region, with a focus on interferon induced innate response |
title_short | A hybrid discrete-continuum model of immune responses to SARS-CoV-2 infection in the lung alveolar region, with a focus on interferon induced innate response |
title_sort | hybrid discrete-continuum model of immune responses to sars-cov-2 infection in the lung alveolar region, with a focus on interferon induced innate response |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9533651/ https://www.ncbi.nlm.nih.gov/pubmed/36208668 http://dx.doi.org/10.1016/j.jtbi.2022.111293 |
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