Bridging spatial scales in respiratory viral infection

Respiratory viruses spread within the host through a combination of local expansion and occasional long-range dissemination that seeds new infection foci. We present LEAP (Lotka-Euler Airway Pathogen model), an analytically tractable within-host model that captures this two-scale process. The model takes the form of an age-dependent branching process and yields a closed-form expression for the exponential growth rate during early infection. Using empirical data to parameterize the model, we find that productive dissemination requires only a small number of successful long-range seeding events per infected cell, with distinct values for SARS-CoV-2 and influenza A virus. LEAP further predicts that, in these well-adapted viruses, interferon-mediated restriction only weakly affects exponential growth, while remaining decisive for poorly adapted pathogens. More broadly, the model provides a flexible framework for experimentally testable predictions of early infection dynamics.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2026-10-20
DOI
https://doi.org/10.1073/pnas.2614436123
Primary Topic
Mathematical and Theoretical Epidemiology and Ecology Models
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article
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article

Bridging spatial scales in respiratory viral infection

Bjarke Frost Nielsen, Kim Sneppen, Ulrik Hvid
Proceedings of the National Academy of Sciences
Mathematical and Theoretical Epidemiology and Ecology Models
article

Bridging spatial scales in respiratory viral infection

Bjarke Frost Nielsen, Kim Sneppen, Ulrik Hvid
article en

Abstract

Respiratory viruses spread within the host through a combination of local expansion and occasional long-range dissemination that seeds new infection foci. We present LEAP (Lotka-Euler Airway Pathogen model), an analytically tractable within-host model that captures this two-scale process. The model takes the form of an age-dependent branching process and yields a closed-form expression for the exponential growth rate during early infection. Using empirical data to parameterize the model, we find that productive dissemination requires only a small number of successful long-range seeding events per infected cell, with distinct values for SARS-CoV-2 and influenza A virus. LEAP further predicts that, in these well-adapted viruses, interferon-mediated restriction only weakly affects exponential growth, while remaining decisive for poorly adapted pathogens. More broadly, the model provides a flexible framework for experimentally testable predictions of early infection dynamics.

Proceedings of the National Academy of SciencesVol. 123(43)
University of Copenhagen (DK)
Openalex Percentile: Top 10%
Mathematical and Theoretical Epidemiology and Ecology Models
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