Mathematical model explains differences in Omicron and Delta SARS-CoV-2 dynamics in Caco-2 and Calu-3 cells
Within-host infection dynamics of Omicron dramatically differs from previous variants of SARS-CoV-2. However, little is still known about which parameters of virus-cell interplay contribute to the observed attenuated replication and pathogenicity of Omicron. Mathematical models, often expressed as s...
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| Format: | Article |
| Language: | English |
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PeerJ Inc.
2024-03-01
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| Series: | PeerJ |
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| Online Access: | https://peerj.com/articles/16964.pdf |
| _version_ | 1797234668497534976 |
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| author | Vladimir Staroverov Alexei Galatenko Evgeny Knyazev Alexander Tonevitsky |
| author_facet | Vladimir Staroverov Alexei Galatenko Evgeny Knyazev Alexander Tonevitsky |
| author_sort | Vladimir Staroverov |
| collection | DOAJ |
| description | Within-host infection dynamics of Omicron dramatically differs from previous variants of SARS-CoV-2. However, little is still known about which parameters of virus-cell interplay contribute to the observed attenuated replication and pathogenicity of Omicron. Mathematical models, often expressed as systems of differential equations, are frequently employed to study the infection dynamics of various viruses. Adopting such models for results of in vitro experiments can be beneficial in a number of aspects, such as model simplification (e.g., the absence of adaptive immune response and innate immunity cells), better measurement accuracy, and the possibility to measure additional data types in comparison with in vivo case. In this study, we consider a refinement of our previously developed and validated model based on a system of integro-differential equations. We fit the model to the experimental data of Omicron and Delta infections in Caco-2 (human intestinal epithelium model) and Calu-3 (lung epithelium model) cell lines. The data include known information on initial conditions, infectious virus titers, and intracellular viral RNA measurements at several time points post-infection. The model accurately explains the experimental data for both variants in both cell lines using only three variant- and cell-line-specific parameters. Namely, the cell entry rate is significantly lower for Omicron, and Omicron triggers a stronger cytokine production rate (i.e., innate immune response) in infected cells, ultimately making uninfected cells resistant to the virus. Notably, differences in only a single parameter (e.g., cell entry rate) are insufficient to obtain a reliable model fit for the experimental data. |
| first_indexed | 2024-04-24T16:35:43Z |
| format | Article |
| id | doaj.art-23fb36fe92a34e2482b29c268689badc |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-04-24T16:35:43Z |
| publishDate | 2024-03-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| series | PeerJ |
| spelling | doaj.art-23fb36fe92a34e2482b29c268689badc2024-03-29T15:05:05ZengPeerJ Inc.PeerJ2167-83592024-03-0112e1696410.7717/peerj.16964Mathematical model explains differences in Omicron and Delta SARS-CoV-2 dynamics in Caco-2 and Calu-3 cellsVladimir Staroverov0Alexei Galatenko1Evgeny Knyazev2Alexander Tonevitsky3Faculty of Mechanics and Mathematics, Lomonosov Moscow State University, Moscow, RussiaFaculty of Mechanics and Mathematics, Lomonosov Moscow State University, Moscow, RussiaFaculty of Biology and Biotechnology, HSE University, Moscow, RussiaFaculty of Biology and Biotechnology, HSE University, Moscow, RussiaWithin-host infection dynamics of Omicron dramatically differs from previous variants of SARS-CoV-2. However, little is still known about which parameters of virus-cell interplay contribute to the observed attenuated replication and pathogenicity of Omicron. Mathematical models, often expressed as systems of differential equations, are frequently employed to study the infection dynamics of various viruses. Adopting such models for results of in vitro experiments can be beneficial in a number of aspects, such as model simplification (e.g., the absence of adaptive immune response and innate immunity cells), better measurement accuracy, and the possibility to measure additional data types in comparison with in vivo case. In this study, we consider a refinement of our previously developed and validated model based on a system of integro-differential equations. We fit the model to the experimental data of Omicron and Delta infections in Caco-2 (human intestinal epithelium model) and Calu-3 (lung epithelium model) cell lines. The data include known information on initial conditions, infectious virus titers, and intracellular viral RNA measurements at several time points post-infection. The model accurately explains the experimental data for both variants in both cell lines using only three variant- and cell-line-specific parameters. Namely, the cell entry rate is significantly lower for Omicron, and Omicron triggers a stronger cytokine production rate (i.e., innate immune response) in infected cells, ultimately making uninfected cells resistant to the virus. Notably, differences in only a single parameter (e.g., cell entry rate) are insufficient to obtain a reliable model fit for the experimental data.https://peerj.com/articles/16964.pdfMathematical modelSARS-CoV-2COVID-19OmicronDeltaCaco-2 |
| spellingShingle | Vladimir Staroverov Alexei Galatenko Evgeny Knyazev Alexander Tonevitsky Mathematical model explains differences in Omicron and Delta SARS-CoV-2 dynamics in Caco-2 and Calu-3 cells PeerJ Mathematical model SARS-CoV-2 COVID-19 Omicron Delta Caco-2 |
| title | Mathematical model explains differences in Omicron and Delta SARS-CoV-2 dynamics in Caco-2 and Calu-3 cells |
| title_full | Mathematical model explains differences in Omicron and Delta SARS-CoV-2 dynamics in Caco-2 and Calu-3 cells |
| title_fullStr | Mathematical model explains differences in Omicron and Delta SARS-CoV-2 dynamics in Caco-2 and Calu-3 cells |
| title_full_unstemmed | Mathematical model explains differences in Omicron and Delta SARS-CoV-2 dynamics in Caco-2 and Calu-3 cells |
| title_short | Mathematical model explains differences in Omicron and Delta SARS-CoV-2 dynamics in Caco-2 and Calu-3 cells |
| title_sort | mathematical model explains differences in omicron and delta sars cov 2 dynamics in caco 2 and calu 3 cells |
| topic | Mathematical model SARS-CoV-2 COVID-19 Omicron Delta Caco-2 |
| url | https://peerj.com/articles/16964.pdf |
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