Epidemic spreading under mutually independent intra- and inter-host pathogen evolution.

The dynamics of epidemic spreading is often reduced to the single control parameter R 0 (reproduction-rate), whose value, above or below unity, determines the state of the contagion. If, however, the pathogen evolves as it spreads, R 0 may change over time, potentially leading to a mutation-driven spread, in which an initially sub-pandemic pathogen undergoes a breakthrough mutation. To predict the boundaries of this pandemic phase, we introduce here a modeling framework to couple the inter-host network spreading patterns with the intra-host evolutionary dynamics. We find that even in the extreme case when these two process are driven by mutually independent selection forces, mutations can still fundamentally alter the pandemic phase-diagram. The pandemic transitions, we show, are now shaped, not just by R 0 , but also by the balance between the epidemic and the evolutionary timescales. If mutations are too slow, the pathogen prevalence decays prior to the appearance of a critical mutation. On the other hand, if mutations are too rapid, the pathogen evolution becomes volatile and, once again, it fails to spread. Between these two extremes, however, we identify a broad range of conditions in which an initially sub-pandemic pathogen can breakthrough to gain widespread prevalence.