Comparing antiviral strategies against COVID-19 via multiscale within-host modelling
© 2021 The Authors..
Within-host models of COVID-19 infection dynamics enable the merits of different forms of antiviral therapy to be assessed in individual patients. A stochastic agent-based model of COVID-19 intracellular dynamics is introduced here, that incorporates essential steps of the viral life cycle targeted by treatment options. Integration of model predictions with an intercellular ODE model of within-host infection dynamics, fitted to patient data, generates a generic profile of disease progression in patients that have recovered in the absence of treatment. This is contrasted with the profiles obtained after variation of model parameters pertinent to the immune response, such as effector cell and antibody proliferation rates, mimicking disease progression in immunocompromised patients. These profiles are then compared with disease progression in the presence of antiviral and convalescent plasma therapy against COVID-19 infections. The model reveals that using both therapies in combination can be very effective in reducing the length of infection, but these synergistic effects decline with a delayed treatment start. Conversely, early treatment with either therapy alone can actually increase the duration of infection, with infectious virions still present after the decline of other markers of infection. This suggests that usage of these treatments should remain carefully controlled in a clinical environment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Royal Society open science - 8(2021), 8 vom: 01. Aug., Seite 210082 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fatehi, F [VerfasserIn] |
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| Links: |
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| Themen: |
Adaptive immune response |
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| Anmerkungen: |
Date Revised 07.11.2023 published: Electronic-eCollection figshare: 10.6084/m9.figshare.c.5542373 Dryad: 10.5061/dryad.sn02v6x38 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1098/rsos.210082 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM329732706 |
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| 520 | |a © 2021 The Authors. | ||
| 520 | |a Within-host models of COVID-19 infection dynamics enable the merits of different forms of antiviral therapy to be assessed in individual patients. A stochastic agent-based model of COVID-19 intracellular dynamics is introduced here, that incorporates essential steps of the viral life cycle targeted by treatment options. Integration of model predictions with an intercellular ODE model of within-host infection dynamics, fitted to patient data, generates a generic profile of disease progression in patients that have recovered in the absence of treatment. This is contrasted with the profiles obtained after variation of model parameters pertinent to the immune response, such as effector cell and antibody proliferation rates, mimicking disease progression in immunocompromised patients. These profiles are then compared with disease progression in the presence of antiviral and convalescent plasma therapy against COVID-19 infections. The model reveals that using both therapies in combination can be very effective in reducing the length of infection, but these synergistic effects decline with a delayed treatment start. Conversely, early treatment with either therapy alone can actually increase the duration of infection, with infectious virions still present after the decline of other markers of infection. This suggests that usage of these treatments should remain carefully controlled in a clinical environment | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a adaptive immune response | |
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| 650 | 4 | |a intracellular infection model | |
| 700 | 1 | |a Bingham, R J |e verfasserin |4 aut | |
| 700 | 1 | |a Dykeman, E C |e verfasserin |4 aut | |
| 700 | 1 | |a Stockley, P G |e verfasserin |4 aut | |
| 700 | 1 | |a Twarock, R |e verfasserin |4 aut | |
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