Abstract

Viruses replicate within cells, but rely on transmission to be sustained in the long term, leading to at least two levels of selection, within and between hosts, which are often in conflict. During the first few months of the COVID -19 pandemic there was a general consensus that selection would be driven by between host transmission because of the short duration of typical SARS -CoV-2 infections. But then Alpha appeared, with its large constellation of mutations and associated transmission advantage, and with that came the proposition that this new variant emerged during a long persistent infection. By using deep sequencing data collected by hospitals during the early phase of the pandemic, and the more than 120,000 sequenced samples we collected as part of the Office for National Statistics COVID -19 Infection Survey, I will walk through the discoveries we have made, ranging from the tiny transmission bottleneck size of SARS -CoV-2, the high prevalence of persistent infections and their link to long Covid, to the balance between within-host evolution, epidemic waves of infection, and patterns of re-infection.