Limited within-host diversity and tight transmission bottlenecks limit SARS-CoV-2 evolution in acutely infected individuals

• Type of Material: Article
• Authors: Katarina Braun, University of Wisconsin; Gage Moreno, University of Wisconsin; Cassia Wagner, Fred Hutchinson Cancer Research Center; Molly A. Accola, University of Wisconsin; William M. Rehrauer, University of Wisconsin; David Baker, University of Wisconsin; Katharina V. Koelle, Emory University; David H. O'Connor, University of Wisconsin; Trevor Bedford, Fred Hutchinson Cancer Research Center; Thomas C. Friedrich, University of Wisconsin; Louise H. Moncla, Fred Hutchinson Cancer Research Center
• Language: English
• Date: 2021-04-30
• Publisher: Cold Spring Harbor Laboratory
• Publication Version: Preprint (Prior to Peer Review)
• Copyright Statement: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1101/2021.04.30.440988
• Title of Journal or Parent Work: bioRxiv
• Keywords: acutely infected host; prolonged infections; immune escape; selection; novel variants; within-host diversity; enhanced transmissibility; divergent SARS-CoV-2 lineages; transmission bottlenecks; genomes
• Research Categories: Biology, Virology; Health Sciences, Immunology

Abstract

The recent emergence of divergent SARS-CoV-2 lineages has raised concerns about the role of selection within individual hosts in propagating novel variants. Of particular concern are variants associated with immune escape and/or enhanced transmissibility. Though growing evidence suggests that novel variants can arise during prolonged infections, most infections are acute. Understanding the extent to which variants emerge and transmit among acutely infected hosts is therefore critical for predicting the pace at which variants resistant to vaccines or conferring increased transmissibility might emerge in the majority of SARS-CoV-2 infections. To characterize how within-host diversity is generated and propagated, we combine extensive laboratory and bioinformatic controls with metrics of within- and between-host diversity to 133 SARS-CoV-2 genomes from acutely infected individuals. We find that within-host diversity during acute infection is low and transmission bottlenecks are narrow, with very few viruses founding most infections. Within-host variants are rarely transmitted, even among individuals within the same household. Accordingly, we also find that within-host variants are rarely detected along phylogenetically linked infections in the broader community. Together, these findings suggest that efficient selection and transmission of novel SARS-CoV-2 variants is unlikely during typical, acute infection.