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Updated: Jan 13, 2026

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SIMPLICITY is an agent-based, multi-scale mathematical model to study SARS-CoV-2 intra- and between-host evolution.

Pietro Gerletti1,2, Nils Gubela3,4, Jean-Baptiste Escudié5

  • 1Center for Artificial Intelligence in Public Health, Robert Koch Institute, Berlin, Germany. simplicity.twisty120@passfwd.com.

Communications Biology
|January 9, 2026
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Summary
This summary is machine-generated.

A new mathematical model, SIMPLICITY, integrates within-host and population-level pathogen dynamics. Simulations show immune escape drives viral evolution and selective sweeps, mimicking SARS-CoV-2 dynamics.

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Area of Science:

  • * Evolutionary biology
  • * Mathematical modeling
  • * Virology

Background:

  • * Computational tools are vital for studying pathogen evolution within hosts and populations.
  • * Existing models often fail to capture the interplay between within-host and between-host evolutionary dynamics.
  • * This gap limits understanding of realistic pathogen evolutionary trajectories.

Purpose of the Study:

  • * To develop a multi-scale mathematical model integrating within-host and population-level dynamics.
  • * To investigate the mechanisms driving severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) evolution.
  • * To explore the impact of immune evasion and waning on viral evolution.

Main Methods:

  • * Developed SIMPLICITY, a multi-scale mathematical model combining within-host disease progression and viral evolution with population-level transmission and immune evasion.
  • * Parameterized the model using SARS-CoV-2 within-host viral dynamics, evolutionary rates, and immune waning data.
  • * Compared a baseline model with an adaptive fitness landscape model incorporating infection history and immune waning.

Main Results:

  • * Simulations demonstrated that escape from population immunity drives evolutionary dynamics.
  • * Observed evolutionary dynamics included selective sweeps, consistent with SARS-CoV-2 evolution.
  • * The adaptive fitness landscape model provided a more realistic representation of evolutionary mechanisms.

Conclusions:

  • * The SIMPLICITY model effectively captures the complex interplay between within-host and population-level pathogen evolution.
  • * Immune escape is a significant driver of viral evolution, leading to selective sweeps.
  • * The model provides insights into the evolutionary mechanisms underlying SARS-CoV-2 adaptation and immune evasion.