Acute SARS-CoV-2 infections harbor limited within-host diversity and transmit via tight transmission bottlenecks

• Type of Material: Article
• Authors: Katarina M Braun, University of Wisconsin-Madison; Gage K Moreno, University of Wisconsin-Madison; Cassia Wagner, Fred Hutchinson Cancer Research Center, Seattle; Molly A Accola, University of Wisconsin-Madison; William M Rehrauer, University of Wisconsin-Madison; David A Baker, University of Wisconsin-Madison; Katia Koelle, Emory University; David H O'Connor, University of Wisconsin-Madison; Trevor Bedford, Fred Hutchinson Cancer Research Center; Thomas C Friedrich, University of Wisconsin-Madison; Louise H Moncla, Fred Hutchinson Cancer Research Center
• Language: English
• Date: 2021-08-23
• Publisher: Public Library of Science (PLoS)
• Publication Version: Final Published Version
• Copyright Statement: © 2021 Braun et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.ppat.1009849
• Title of Journal or Parent Work: PLoS Pathogens
• Volume: 17
• Issue: 8
• Grant/Funding Information: LHM is supported by NIAID grant number K99 AI147029-01. GKM is supported by an NLM training grant to the Computation and Informatics in Biology and Medicine Training Program (NLM 5T15LM007359). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: tight transmission bottlenecks; SARS-CoV-2
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

The emergence of divergent SARS-CoV-2 lineages has raised concern that novel variants eliciting immune escape or the ability to displace circulating lineages could emerge within individual hosts. Though growing evidence suggests that novel variants arise during prolonged infections, most infections are acute. Understanding how efficiently variants emerge and transmit among acutely-infected hosts is therefore critical for predicting the pace of long-term SARS-CoV-2 evolution. 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 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, and are rarely detected along phylogenetically linked infections in the broader community. These findings suggest that most variation generated within-host is lost during transmission.