The Omicron BA.1 variant of SARS-CoV-2 was more transmissible and less severe than the preceding Delta variant, including in hosts without previous infection or vaccination. To investigate why this was the case, we conducted in vitro replication experiments in human nasal and lung cells, then constructed and fitted ODE models of varying levels of complexity to the data, using Markov chain Monte Carlo methods. Our results fitting a simple model suggest that the basic reproduction number and growth rate are higher for Omicron in nasal cells, and higher for Delta in lung cells. As growth in nasal cells is thought to correspond to transmissibility and growth in lung cells is thought to correspond to severity, these results are consistent with epidemiological and clinical observations. We then fitted a more complex model, including different virus entry pathways and the immune response, to the data, to understand the mechanisms leading to higher infectivity for Omicron in nasal cells. This work paves the way for using within-host mathematical models to analyse experimental data and understand the transmission potential of future variants.

While presenting the results of this study, I will use them to open a wider discussion on common problems in mathematical biology, such as the situations in which complex models are preferable to simpler models; when it is appropriate to fix model parameters; and how to present results which are contingent on unidentifiable parameters.