%0 Journal Article %A Mireille Farjo %A Katia Koelle %A Michael A. Martin %A Laura L. Gibson %A Kimberly K.O. Walden %A Gloria Rendon %A Christopher J. Fields %A Fadi G. Alnaji %A Nicholas Gallagher %A Chun Huai Luo %A Heba H. Mostafa %A Yukari C. Manabe %A Andrew Pekosz %A Rebecca L. Smith %A David D. McManus %A Christopher B. Brooke %T Within-host evolutionary dynamics and tissue compartmentalization during acute SARS-CoV-2 infection %D 2022 %R 10.1101/2022.06.21.497047 %J bioRxiv %P 2022.06.21.497047 %X The global evolution of SARS-CoV-2 depends in part upon the evolutionary dynamics within individual hosts with varying immune histories. To characterize the within-host evolution of acute SARS-CoV-2 infection, we deep sequenced saliva and nasal samples collected daily from immune and unvaccinated individuals early during infection. We show that longitudinal sampling facilitates high-confidence genetic variant detection and reveals evolutionary dynamics missed by less-frequent sampling strategies. Within-host dynamics in both naïve and immune individuals appeared largely stochastic; however, we identified clear mutational hotspots within the viral genome, consistent with selection and differing between naïve and immune individuals. In rare cases, minor genetic variants emerged to frequencies sufficient for forward transmission. Finally, we detected significant genetic compartmentalization of virus between saliva and nasal swab sample sites in many individuals. Altogether, these data provide a high-resolution profile of within-host SARS-CoV-2 evolutionary dynamics.Competing Interest StatementThe authors have declared no competing interest. %U https://www.biorxiv.org/content/biorxiv/early/2022/06/23/2022.06.21.497047.full.pdf