RT Journal Article SR Electronic T1 Within-host evolutionary dynamics and tissue compartmentalization during acute SARS-CoV-2 infection JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.06.21.497047 DO 10.1101/2022.06.21.497047 A1 Mireille Farjo A1 Katia Koelle A1 Michael A. Martin A1 Laura L. Gibson A1 Kimberly K.O. Walden A1 Gloria Rendon A1 Christopher J. Fields A1 Fadi G. Alnaji A1 Nicholas Gallagher A1 Chun Huai Luo A1 Heba H. Mostafa A1 Yukari C. Manabe A1 Andrew Pekosz A1 Rebecca L. Smith A1 David D. McManus A1 Christopher B. Brooke YR 2022 UL http://biorxiv.org/content/early/2022/06/23/2022.06.21.497047.abstract AB 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.