Non-pharmaceutical interventions and the emergence of pathogen variants

AO_SCPLOWBSTRACTC_SCPLOWNon-pharmaceutical interventions (NPIs), such as social distancing and contact tracing, have been widely implemented during the COVID-19 pandemic. In addition to playing an important role in suppressing transmission, NPIs influence pathogen evolution by mediating mutation supply and altering the strength of selection for novel variants. However, it is unclear how NPIs might affect the emergence of novel variants of concern that are able to escape pre-existing immunity (partially or fully), are more transmissible, or cause greater mortality. Here, we analyse a stochastic two-strain epidemiological model to determine how the strength of NPIs affects the emergence of variants with similar or contrasting life-history characteristics to the wildtype. We show that, while stronger and timelier NPIs generally reduce the likelihood of variant emergence, it is possible for more transmissible variants with high cross immunity to have a greater probability of emerging at intermediate levels of NPIs. However, since one cannot predict the characteristics of a variant, the best strategy to prevent emergence is likely to be implementation of strong, timely NPIs. AO_SCPLOWUTHORC_SCPLOWO_SCPCAP C_SCPCAPO_SCPLOWSUMMARYC_SCPLOWDuring the COVID-19 pandemic, a wide range of non-pharmaceutical interventions, including mask wearing, quarantine, isolation, and lockdowns, have been used by governments around the world to suppress virus transmission. Although considerable efforts have been made to understand how such interventions affect transmission, much less attention has been paid to their effects on pathogen evolution. While vaccines are well-known to affect virus evolution, non-pharmaceutical interventions also influence mutation supply and the strength of selection, and hence play a key role in the emergence of novel variants. Here, we use a relatively simple mathematical model to explore how non-pharmaceutical interventions during an epidemic affect the emergence of a novel variant of a pathogen. We show that in general, it is important to implement effective transmission-reducing public health measures in a timely manner to prevent the emergence of novel variants, which may be more transmissible, more deadly, or able to escape immunity.